Showing papers in "Microbiology spectrum in 2018"
TL;DR: WHO recently has launched new guidelines on the use of medically important antimicrobials in food-producing animals, recommending that farmers and the food industry stop using antimicroBials routinely to promote growth and prevent disease in healthy animals.
Abstract: One Health is the collaborative effort of multiple health science professions to attain optimal health for people, domestic animals, wildlife, plants, and our environment. The drivers of antimicrobial resistance include antimicrobial use and abuse in human, animal, and environmental sectors and the spread of resistant bacteria and resistance determinants within and between these sectors and around the globe. Most of the classes of antimicrobials used to treat bacterial infections in humans are also used in animals. Given the important and interdependent human, animal, and environmental dimensions of antimicrobial resistance, it is logical to take a One Health approach when addressing this problem. This includes taking steps to preserve the continued effectiveness of existing antimicrobials by eliminating their inappropriate use and by limiting the spread of infection. Major concerns in the animal health and agriculture sectors are mass medication of animals with antimicrobials that are critically important for humans, such as third-generation cephalosporins and fluoroquinolones, and the long-term, in-feed use of medically important antimicrobials, such as colistin, tetracyclines, and macrolides, for growth promotion. In the human sector it is essential to prevent infections, reduce over-prescribing of antimicrobials, improve sanitation, and improve hygiene and infection control. Pollution from inadequate treatment of industrial, residential, and farm waste is expanding the resistome in the environment. Numerous countries and several international agencies have included a One Health approach within their action plans to address antimicrobial resistance. Necessary actions include improvements in antimicrobial use regulation and policy, surveillance, stewardship, infection control, sanitation, animal husbandry, and alternatives to antimicrobials. WHO recently has launched new guidelines on the use of medically important antimicrobials in food-producing animals, recommending that farmers and the food industry stop using antimicrobials routinely to promote growth and prevent disease in healthy animals. These guidelines aim to help preserve the effectiveness of antimicrobials that are important for human medicine by reducing their use in animals.
489 citations
TL;DR: Of note, coselection and persistence of resistances to critically important antimicrobial agents in human medicine also occurs through the massive use of antimicrobialagents in veterinary medicine, such as tetracyclines or sulfonamides, as long as all those determinants are located on the same genetic elements.
Abstract: Multidrug resistance in Escherichia coli has become a worrying issue that is increasingly observed in human but also in veterinary medicine worldwide. E. coli is intrinsically susceptible to almost all clinically relevant antimicrobial agents, but this bacterial species has a great capacity to accumulate resistance genes, mostly through horizontal gene transfer. The most problematic mechanisms in E. coli correspond to the acquisition of genes coding for extended-spectrum β-lactamases (conferring resistance to broad-spectrum cephalosporins), carbapenemases (conferring resistance to carbapenems), 16S rRNA methylases (conferring pan-resistance to aminoglycosides), plasmid-mediated quinolone resistance (PMQR) genes (conferring resistance to [fluoro]quinolones), and mcr genes (conferring resistance to polymyxins). Although the spread of carbapenemase genes has been mainly recognized in the human sector but poorly recognized in animals, colistin resistance in E. coli seems rather to be related to the use of colistin in veterinary medicine on a global scale. For the other resistance traits, their cross-transfer between the human and animal sectors still remains controversial even though genomic investigations indicate that extended-spectrum β-lactamase producers encountered in animals are distinct from those affecting humans. In addition, E. coli of animal origin often also show resistances to other-mostly older-antimicrobial agents, including tetracyclines, phenicols, sulfonamides, trimethoprim, and fosfomycin. Plasmids, especially multiresistance plasmids, but also other mobile genetic elements, such as transposons and gene cassettes in class 1 and class 2 integrons, seem to play a major role in the dissemination of resistance genes. Of note, coselection and persistence of resistances to critically important antimicrobial agents in human medicine also occurs through the massive use of antimicrobial agents in veterinary medicine, such as tetracyclines or sulfonamides, as long as all those determinants are located on the same genetic elements.
362 citations
TL;DR: The different oral environments inhabited by streptococci and the species that occupy each niche are discussed, with special attention to the taxonomy of Streptococcus, which is now divided into eight distinct groups.
Abstract: Bacteria belonging to the genus Streptococcus are the first inhabitants of the oral cavity, which can be acquired right after birth and thus play an important role in the assembly of the oral microbiota. In this article, we discuss the different oral environments inhabited by streptococci and the species that occupy each niche. Special attention is given to the taxonomy of Streptococcus, because this genus is now divided into eight distinct groups, and oral species are found in six of them. Oral streptococci produce an arsenal of adhesive molecules that allow them to efficiently colonize different tissues in the mouth. Also, they have a remarkable ability to metabolize carbohydrates via fermentation, thereby generating acids as byproducts. Excessive acidification of the oral environment by aciduric species such as Streptococcus mutans is directly associated with the development of dental caries. However, less acid-tolerant species such as Streptococcus salivarius and Streptococcus gordonii produce large amounts of alkali, displaying an important role in the acid-base physiology of the oral cavity. Another important characteristic of certain oral streptococci is their ability to generate hydrogen peroxide that can inhibit the growth of S. mutans. Thus, oral streptococci can also be beneficial to the host by producing molecules that are inhibitory to pathogenic species. Lastly, commensal and pathogenic streptococci residing in the oral cavity can eventually gain access to the bloodstream and cause systemic infections such as infective endocarditis.
231 citations
TL;DR: A synopsis and perspective of the contributions made by RNase E to sustain robust gene regulation with speed and accuracy is provided.
Abstract: The bacterial endoribonuclease RNase E occupies a pivotal position in the control of gene expression, as its actions either commit transcripts to an irreversible fate of rapid destruction or unveil their hidden functions through specific processing. Moreover, the enzyme contributes to quality control of rRNAs. The activity of RNase E can be directed and modulated by signals provided through regulatory RNAs that guide the enzyme to specific transcripts that are to be silenced. Early in its evolutionary history, RNase E acquired a natively unfolded appendage that recruits accessory proteins and RNA. These accessory factors facilitate the activity of RNase E and include helicases that remodel RNA and RNA-protein complexes, and polynucleotide phosphorylase, a relative of the archaeal and eukaryotic exosomes. RNase E also associates with enzymes from central metabolism, such as enolase and aconitase. RNase E-based complexes are diverse in composition, but generally bear mechanistic parallels with eukaryotic machinery involved in RNA-induced gene regulation and transcript quality control. That these similar processes arose independently underscores the universality of RNA-based regulation in life. Here we provide a synopsis and perspective of the contributions made by RNase E to sustain robust gene regulation with speed and accuracy.
157 citations
TL;DR: The diversity of enterococcal species and their distribution in the intestinal tract of animals and the epidemiology of multidrug-resistant enterococci of animal origin are analyzed, with special attention given to beta-lactams, glycopeptides, and linezolid.
Abstract: Enterococci are natural inhabitants of the intestinal tract in humans and many animals, including food-producing and companion animals They can easily contaminate the food and the environment, entering the food chain Moreover, Enterococcus is an important opportunistic pathogen, especially the species E faecalis and E faecium, causing a wide variety of infections This microorganism not only contains intrinsic resistance mechanisms to several antimicrobial agents, but also has the capacity to acquire new mechanisms of antimicrobial resistance In this review we analyze the diversity of enterococcal species and their distribution in the intestinal tract of animals Moreover, resistance mechanisms for different classes of antimicrobials of clinical relevance are reviewed, as well as the epidemiology of multidrug-resistant enterococci of animal origin, with special attention given to beta-lactams, glycopeptides, and linezolid The emergence of new antimicrobial resistance genes in enterococci of animal origin, such as optrA and cfr, is highlighted The molecular epidemiology and the population structure of E faecalis and E faecium isolates in farm and companion animals is presented Moreover, the types of plasmids that carry the antimicrobial resistance genes in enterococci of animal origin are reviewed
120 citations
TL;DR: The sequence-specific RNA binding protein CsrA is employed by diverse bacteria in the posttranscriptional regulation of gene expression, and its binding interactions with RNA have been documented at atomic resolution and shown to alter RNA secondary structure, RNA stability, translation, and/or Rho-mediated transcription termination through a growing number of molecular mechanisms.
Abstract: The sequence-specific RNA binding protein CsrA is employed by diverse bacteria in the posttranscriptional regulation of gene expression. Its binding interactions with RNA have been documented at atomic resolution and shown to alter RNA secondary structure, RNA stability, translation, and/or Rho-mediated transcription termination through a growing number of molecular mechanisms. In Gammaproteobacteria, small regulatory RNAs (sRNAs) that contain multiple CsrA binding sites compete with mRNA for binding to CsrA, thereby sequestering and antagonizing this protein. Both the synthesis and turnover of these sRNAs are regulated, allowing CsrA activity to be rapidly and efficiently adjusted in response to nutritional conditions and stresses. Feedback loops between the Csr regulatory components improve the dynamics of signal response by the Csr system. The Csr system of Escherichia coli is intimately interconnected with other global regulatory systems, permitting it to contribute to regulation by those systems. In some species, a protein antagonist of CsrA functions as part of a checkpoint for flagellum biosynthesis. In other species, a protein antagonist participates in a mechanism in which a type III secretion system is used for sensing interactions with host cells. Recent transcriptomics studies reveal vast effects of CsrA on gene expression through direct binding to hundreds of mRNAs, and indirectly through its effects on the expression of dozens of transcription factors. CsrA binding to base-pairing sRNAs and novel mRNA segments, such as the 3' untranslated region and deep within coding regions, predict its participation in yet-to-be-discovered regulatory mechanisms.
119 citations
TL;DR: Standardization of methods used for determination of susceptibility levels is difficult since no quality control strains are available and because of species-specific growth requirements, and specific breakpoints for animal mycoplasmas should be determined so that in vitro information can be used to provide advice on selection of in vivo treatments.
Abstract: Mycoplasmas are intrinsically resistant to antimicrobials targeting the cell wall (fosfomycin, glycopeptides, or β-lactam antibiotics) and to sulfonamides, first-generation quinolones, trimethoprim, polymixins, and rifampicin. The antibiotics most frequently used to control mycoplasmal infections in animals are macrolides and tetracyclines. Lincosamides, fluoroquinolones, pleuromutilins, phenicols, and aminoglycosides can also be active. Standardization of methods used for determination of susceptibility levels is difficult since no quality control strains are available and because of species-specific growth requirements. Reduced susceptibility levels or resistances to several families of antimicrobials have been reported in field isolates of pathogenic Mycoplasma species of major veterinary interest: M. gallisepticum and M. synoviae in poultry; M. hyopneumoniae, M. hyorhinis, and M. hyosynoviae in swine; M. bovis in cattle; and M. agalactiae in small ruminants. The highest resistances are observed for macrolides, followed by tetracyclines. Most strains remain susceptible to fluoroquinolones. Pleuromutilins are the most effective antibiotics in vitro. Resistance frequencies vary according to the Mycoplasma species but also according to the countries or groups of animals from which the samples were taken. Point mutations in the target genes of different antimicrobials have been identified in resistant field isolates, in vitro-selected mutants, or strains reisolated after an experimental infection followed by one or several treatments: DNA-gyrase and topoisomerase IV for fluoroquinolones; 23S rRNA for macrolides, lincosamides, pleuromutilins, and amphenicols; 16S rRNAs for tetracyclines and aminoglycosides. Further work should be carried out to determine and harmonize specific breakpoints for animal mycoplasmas so that in vitro information can be used to provide advice on selection of in vivo treatments.
108 citations
TL;DR: The identification of plasmids in terrestrial pathogens (Salmonella enterica serotypes, Escherichia coli, and others) which have considerable homology toplasmid backbone DNA from aquatic pathogens suggests that the plasmid profiles of fish pathogens are extremely plastic and mobile and constitute a considerable reservoir for antimicrobial resistance genes for pathogens in diverse environments.
Abstract: Major concerns surround the use of antimicrobial agents in farm-raised fish, including the potential impacts these uses may have on the development of antimicrobial-resistant pathogens in fish and the aquatic environment. Currently, some antimicrobial agents commonly used in aquaculture are only partially effective against select fish pathogens due to the emergence of resistant bacteria. Although reports of ineffectiveness in aquaculture due to resistant pathogens are scarce in the literature, some have reported mass mortalities in Penaeus monodon larvae caused by Vibrio harveyi resistant to trimethoprim-sulfamethoxazole, chloramphenicol, erythromycin, and streptomycin. Genetic determinants of antimicrobial resistance have been described in aquaculture environments and are commonly found on mobile genetic elements which are recognized as the primary source of antimicrobial resistance for important fish pathogens. Indeed, resistance genes have been found on transferable plasmids and integrons in pathogenic bacterial species in the genera Aeromonas, Yersinia, Photobacterium, Edwardsiella, and Vibrio. Class 1 integrons and IncA/C plasmids have been widely identified in important fish pathogens (Aeromonas spp., Yersinia spp., Photobacterium spp., Edwardsiella spp., and Vibrio spp.) and are thought to play a major role in the transmission of antimicrobial resistance determinants in the aquatic environment. The identification of plasmids in terrestrial pathogens (Salmonella enterica serotypes, Escherichia coli, and others) which have considerable homology to plasmid backbone DNA from aquatic pathogens suggests that the plasmid profiles of fish pathogens are extremely plastic and mobile and constitute a considerable reservoir for antimicrobial resistance genes for pathogens in diverse environments.
94 citations
TL;DR: The mechanisms and molecular epidemiology of the major types of resistance to antimicrobials encountered in the most important streptococcal species in veterinary medicine are considered.
Abstract: The genus Streptococcus includes Gram-positive organisms shaped in cocci and organized in chains. They are commensals, pathogens, and opportunistic pathogens for humans and animals. Most Streptococcus species of veterinary relevance have a specific ecological niche, such as S. uberis, which is almost exclusively an environmental pathogen causing bovine mastitis. In contrast, S. suis can be considered as a true zoonotic pathogen, causing specific diseases in humans after contact with infected animals or derived food products. Finally, Streptococcus species such as S. agalactiae can be sporadically zoonotic, even though they are pathogens of both humans and animals independently. For clarification, a short taxonomical overview will be given here to highlight the diversity of streptococci that infect animals. Several families of antibiotics are used to treat animals for streptococcal infections. First-line treatments are penicillins (alone or in combination with aminoglycosides), macrolides and lincosamides, fluoroquinolones, and tetracyclines. Because of the selecting role of antibiotics, resistance phenotypes have been reported in streptococci isolated from animals worldwide. Globally, the dynamic of resistance acquisition in streptococci is slower than what is experienced in Enterobacteriaceae, probably due to the much more limited horizontal spread of resistance genes. Nonetheless, transposons or integrative and conjugative elements can disseminate resistance determinants among streptococci. Besides providing key elements on the prevalence of resistance in streptococci from animals, this article will also largely consider the mechanisms and molecular epidemiology of the major types of resistance to antimicrobials encountered in the most important streptococcal species in veterinary medicine.
83 citations
TL;DR: In this chapter, recent Salmonella antibiotic susceptibility data from Europe and the US are compared and the state of known resistance genes that have been identified in the genus are summarized.
Abstract: Non-typhoidal Salmonella is the most common foodborne bacterial pathogen in most countries. It is widely present in food animal species, and therefore blocking its transmission through the food supply is a prominent focus of food safety activities worldwide. Antibiotic resistance in non-typhoidal Salmonella arises in large part because of antibiotic use in animal husbandry. Tracking resistance in Salmonella is required to design targeted interventions to contain or diminish resistance and refine use practices in production. Many countries have established systems to monitor antibiotic resistance in Salmonella and other bacteria, the earliest ones appearing the Europe and the US. In this chapter, we compare recent Salmonella antibiotic susceptibility data from Europe and the US. In addition, we summarize the state of known resistance genes that have been identified in the genus. The advent of routine whole genome sequencing has made it possible to conduct genomic surveillance of resistance based on DNA sequences alone. This points to a new model of surveillance in the future that will provide more definitive information on the sources of resistant Salmonella, the specific types of resistance genes involved, and information on how resistance spreads.
82 citations
TL;DR: The goal of this article is to give an overview of the resistance phenotypes described in these pathogens and to provide a comprehensive analysis of all data that have been reported on Acinetobacter s.
Abstract: The nonfermenting bacteria belonging to Acinetobacter spp. and Pseudomonas spp. are capable of colonizing both humans and animals and can also be opportunistic pathogens. More specifically, the species Acinetobacter baumannii and Pseudomonas aeruginosa have been recurrently reported as multidrug-resistant and even pandrug-resistant in clinical isolates. Both species were categorized among the ESKAPE pathogens, ESKAPE standing for Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, A. baumannii, P. aeruginosa, and Enterobacter species. These six pathogens are the major cause of nosocomial infections in the United States and are a threat all over the world because of their capacity to become increasingly resistant to all available antibiotics. A. baumannii and P. aeruginosa are both intrinsically resistant to many antibiotics due to complementary mechanisms, the main ones being the low permeability of their outer membrane, the production of the AmpC beta-lactamase, and the production of several efflux systems belonging to the resistance-nodulation-cell division family. In addition, they are both capable of acquiring multiple resistance determinants, such as beta-lactamases or carbapenemases. Even if such enzymes have rarely been identified in bacteria of animal origin, they may sooner or later spread to this reservoir. The goal of this article is to give an overview of the resistance phenotypes described in these pathogens and to provide a comprehensive analysis of all data that have been reported on Acinetobacter spp. and Pseudomonas spp. from animal hosts.
TL;DR: An overview about the occurrence of antisense transcription in bacteria is given, particular examples of functionally characterized asRNAs are highlighted, and recent evidence pointing at global relevance in RNA processing and transcription-coupled DNA repair is discussed.
Abstract: Although bacterial genomes are usually densely protein-coding, genome-wide mapping approaches of transcriptional start sites revealed that a significant fraction of the identified promoters drive the transcription of noncoding RNAs. These can be trans-acting RNAs, mainly originating from intergenic regions and, in many studied examples, possessing regulatory functions. However, a significant fraction of these noncoding RNAs consist of natural antisense transcripts (asRNAs), which overlap other transcriptional units. Naturally occurring asRNAs were first observed to play a role in bacterial plasmid replication and in bacteriophage λ more than 30 years ago. Today's view is that asRNAs abound in all three domains of life. There are several examples of asRNAs in bacteria with clearly defined functions. Nevertheless, many asRNAs appear to result from pervasive initiation of transcription, and some data point toward global functions of such widespread transcriptional activity, explaining why the search for a specific regulatory role is sometimes futile. In this review, we give an overview about the occurrence of antisense transcription in bacteria, highlight particular examples of functionally characterized asRNAs, and discuss recent evidence pointing at global relevance in RNA processing and transcription-coupled DNA repair.
TL;DR: Much has been learned about this unusual RNA, its mechanism of action, and how it is regulated; yet much still remains to be investigated, especially regarding potential differences in behavior of 6S RNAs in diverse bacteria.
Abstract: 6S RNA is a small RNA regulator of RNA polymerase (RNAP) that is present broadly throughout the bacterial kingdom. Initial functional studies in Escherichia coli revealed that 6S RNA forms a complex with RNAP resulting in regulation of transcription, and cells lacking 6S RNA have altered survival phenotypes. The last decade has focused on deepening the understanding of several aspects of 6S RNA activity, including (i) addressing questions of how broadly conserved 6S RNAs are in diverse organisms through continued identification and initial characterization of divergent 6S RNAs; (ii) the nature of the 6S RNA-RNAP interaction through examination of variant proteins and mutant RNAs, cross-linking approaches, and ultimately a cryo-electron microscopic structure; (iii) the physiological consequences of 6S RNA function through identification of the 6S RNA regulon and promoter features that determine 6S RNA sensitivity; and (iv) the mechanism and cellular impact of 6S RNA-directed synthesis of product RNAs (i.e., pRNA synthesis). Much has been learned about this unusual RNA, its mechanism of action, and how it is regulated; yet much still remains to be investigated, especially regarding potential differences in behavior of 6S RNAs in diverse bacteria.
TL;DR: This chapter describes in detail the mechanisms so far encountered for the various classes of antimicrobial agents and describes the main mechanisms include enzymatic inactivation, reduced intracellular accumulation, and modifications at the cellular target sites.
Abstract: During the past decades resistance to virtually all antimicrobial agents has been observed in bacteria of animal origin. This chapter describes in detail the mechanisms so far encountered for the various classes of antimicrobial agents. The main mechanisms include enzymatic inactivation by either disintegration or chemical modification of antimicrobial agents, reduced intracellular accumulation by either decreased influx or increased efflux of antimicrobial agents, and modifications at the cellular target sites (i.e., mutational changes, chemical modification, protection, or even replacement of the target sites). Often several mechanisms interact to enhance bacterial resistance to antimicrobial agents. This is a completely revised version of the corresponding chapter in the book Antimicrobial Resistance in Bacteria of Animal Origin published in 2006. New sections have been added for oxazolidinones, polypeptides, mupirocin, ansamycins, fosfomycin, fusidic acid, and streptomycins, and the chapters for the remaining classes of antimicrobial agents have been completely updated to cover the advances in knowledge gained since 2006.
TL;DR: This review summarizes the present knowledge on virulence-related RNATs and discusses recent developments in the field to fine-tune virulence gene expression when the pathogen enters or exits the body of its host.
Abstract: Temperature variation is one of the multiple parameters a microbial pathogen encounters when it invades a warm-blooded host. To survive and thrive at host body temperature, human pathogens have developed various strategies to sense and respond to their ambient temperature. An instantaneous response is mounted by RNA thermometers (RNATs), which are integral sensory structures in mRNAs that modulate translation efficiency. At low temperatures outside the host, the folded RNA blocks access of the ribosome to the translation initiation region. The temperature shift upon entering the host destabilizes the RNA structure and thus permits ribosome binding. This reversible zipper-like mechanism of RNATs is ideally suited to fine-tune virulence gene expression when the pathogen enters or exits the body of its host. This review summarizes our present knowledge on virulence-related RNATs and discusses recent developments in the field.
TL;DR: How Campylobacter resists the action of various classes of antimicrobials is discussed, with an emphasis on newly discovered mechanisms that are horizontally transferable and greatly facilitate the adaptation of Campyloblacter in the food-producing environments where antibiotics are frequently used.
Abstract: Campylobacter is a major foodborne pathogen and has become increasingly resistant to clinically important antimicrobials. To cope with the selection pressure from antimicrobial use in both veterinary and human medicine, Campylobacter has developed multiple mechanisms for antibiotic resistance, including modification or mutation of antimicrobial targets, modification or inactivation of antibiotics, and reduced drug accumulation by drug efflux pumps. Some of these mechanisms confer resistance to a specific class of antimicrobials, while others give rise to multidrug resistance. Notably, new antibiotic resistance mechanisms continuously emerge in Campylobacter, and some examples include the recently discovered multidrug resistance genomic islands harboring multiple genes involved in the resistance to aminoglycosides and macrolides, a novel Cfr(C) conferring resistance to phenicols and other drugs, and a potent multidrug efflux pump CmeABC variant (RE-CmeABC) that shows a significantly enhanced function in multidrug resistance and is associated with exceedingly high-level resistance to fluoroquinolones. These newly emerged resistance mechanisms are horizontally transferable and greatly facilitate the adaptation of Campylobacter in the food-producing environments where antibiotics are frequently used. In this article, we will discuss how Campylobacter resists the action of various classes of antimicrobials, with an emphasis on newly discovered mechanisms.
TL;DR: This article aims to provide an understanding of the development of antimicrobial resistance in bacteria following a biocide exposure and provides evidence of the occurrence of bacterial resistance and its mechanisms of action.
Abstract: Biocides and formulated biocides are used worldwide for an increasing number of applications despite tightening regulations in Europe and in the United States. One concern is that such intense usage of biocides could lead to increased bacterial resistance to a product and cross-resistance to unrelated antimicrobials including chemotherapeutic antibiotics. Evidence to justify such a concern comes mostly from the use of health care-relevant bacterial isolates, although the number of studies of the resistance characteristics of veterinary isolates to biocides have increased the past few years. One problem remains the definition of "resistance" and how to measure resistance to a biocide. This has yet to be addressed globally, although the measurement of resistance is becoming more pressing, with regulators both in Europe and in the United States demanding that manufacturers provide evidence that their biocidal products will not impact on bacterial resistance. Alongside in vitro evidence of potential antimicrobial cross-resistance following biocide exposure, our understanding of the mechanisms of bacterial resistance and, more recently, our understanding of the effect of biocides to induce a mechanism(s) of resistance in bacteria has improved. This article aims to provide an understanding of the development of antimicrobial resistance in bacteria following a biocide exposure. The sections provide evidence of the occurrence of bacterial resistance and its mechanisms of action and debate how to measure bacterial resistance to biocides. Examples pertinent to the veterinary field are used where appropriate.
TL;DR: This review will summarize knowledge on how sRNAs control iron homeostasis mainly through studies on RyhB in Escherichia coli, and the parallel roles and modes of action of other s RNAs in different bacteria will be described.
Abstract: While iron is essential to sustain growth, its excess can be detrimental to the cell by generating highly toxic reactive oxygen species. Regulation of iron homeostasis thus plays a vital role in almost all living organisms. During the last 15 years, the small RNA (sRNA) RyhB has been shown to be a key actor of iron homeostasis regulation in bacteria. Through multiple molecular mechanisms, RyhB represses expendable iron-utilizing proteins, promotes siderophore production, and coordinates Fe-S cluster cofactor biogenesis, thereby establishing a so-called iron-sparing response. In this review, we will summarize knowledge on how sRNAs control iron homeostasis mainly through studies on RyhB in Escherichia coli. The parallel roles and modes of action of other sRNAs in different bacteria will also be described. Finally, we will discuss what questions remain to be answered concerning this important stress response regulation by sRNAs.
TL;DR: These different protein families use common strategies for disrupting or annealing RNA double helices, which can be used to understand the mechanisms by which proteins chaperone RNA-dependent regulation in bacteria.
Abstract: RNA-binding proteins chaperone the biological functions of noncoding RNA by reducing RNA misfolding, improving matchmaking between regulatory RNA and targets, and exerting quality control over RNP biogenesis. Recent studies of Escherichia coli CspA, HIV NCp, and E. coli Hfq are beginning to show how RNA-binding proteins remodel RNA structures. These different protein families use common strategies for disrupting or annealing RNA double helices, which can be used to understand the mechanisms by which proteins chaperone RNA-dependent regulation in bacteria.
TL;DR: The Gram-positive pathogen Listeria monocytogenes is able to promote its entry into a diverse range of mammalian host cells by triggering plasma membrane remodeling, leading to bacterial engulfment.
Abstract: The Gram-positive pathogen Listeria monocytogenes is able to promote its entry into a diverse range of mammalian host cells by triggering plasma membrane remodeling, leading to bacterial engulfment. Upon cell invasion, L. monocytogenes disrupts its internalization vacuole and translocates to the cytoplasm, where bacterial replication takes place. Subsequently, L. monocytogenes uses an actin-based motility system that allows bacterial cytoplasmic movement and cell-to-cell spread. L. monocytogenes therefore subverts host cell receptors, organelles and the cytoskeleton at different infection steps, manipulating diverse cellular functions that include ion transport, membrane trafficking, post-translational modifications, phosphoinositide production, innate immune responses as well as gene expression and DNA stability.
TL;DR: An overview of current use in the European Union and the United States, detected metal resistance determinants, and the proteins and mechanisms responsible for conferring copper and zinc resistance in bacteria is provided.
Abstract: Metals and metalloids have been used alongside antibiotics in livestock production for a long time. The potential and acute negative impact on the environment and human health of these livestock feed supplements has prompted lawmakers to ban or discourage the use of some or all of these supplements. This article provides an overview of current use in the European Union and the United States, detected metal resistance determinants, and the proteins and mechanisms responsible for conferring copper and zinc resistance in bacteria. A detailed description of the most common copper and zinc metal resistance determinants is given to illustrate not only the potential danger of coselecting antibiotic resistance genes but also the potential to generate bacterial strains with an increased potential to be pathogenic to humans. For example, the presence of a 20-gene copper pathogenicity island is highlighted since bacteria containing this gene cluster could be readily isolated from copper-fed pigs, and many pathogenic strains, including Escherichia coli O104:H4, contain this potential virulence factor, suggesting a potential link between copper supplements in livestock and the evolution of pathogens.
TL;DR: Key learning from the experiences of antimicrobial stewardship programs in human medicine are summarized in this article-guiding the development of a stewardship framework suitable for adaptation and use in both companion animal and livestock practice.
Abstract: While antimicrobial resistance is already a public health crisis in human medicine, therapeutic failure in veterinary medicine due to antimicrobial resistance remains relatively uncommon. However, there are many pathways by which antimicrobial resistance determinants can travel between animals and humans: by close contact, through the food chain, or indirectly via the environment. Antimicrobial stewardship describes measures that can help mitigate the public health crisis and preserve the effectiveness of available antimicrobial agents. Antimicrobial stewardship programs have been principally developed, implemented, and studied in human hospitals but are beginning to be adapted for other applications in human medicine. Key learning from the experiences of antimicrobial stewardship programs in human medicine are summarized in this article-guiding the development of a stewardship framework suitable for adaptation and use in both companion animal and livestock practice. The antimicrobial stewardship program for veterinary use integrates infection prevention and control together with approaches emphasizing avoidance of antimicrobial agents. The 5R framework of continuous improvement that is described recognizes the importance of executive support; highly motivated organizations and teams (responsibility); the need to review the starting position, set objectives, and determine means of measuring progress and success; and a critical focus on reducing, replacing, and refining the use of antimicrobial agents. Significant issues that are currently the focus of intensive research include improved detection and diagnosis of infections, refined dosing regimens that are simultaneously effective while not selecting resistance, searches for alternatives to antimicrobial agents, and development of improved vaccines to enhance immunity and reduce disease.
TL;DR: It is proposed that exaptation, a process by which achange of function is achieved by a change of habitat and not by changes in the element with the new functionality, is the basis of the evolution of virulence determinants and of antibiotic resistance genes.
Abstract: Inspection of the genomes of bacterial pathogens indicates that their pathogenic potential relies, at least in part, on the activity of different elements that have been acquired by horizontal gene transfer from other (usually unknown) microorganisms. Similarly, in the case of resistance to antibiotics, besides mutation-driven resistance, the incorporation of novel resistance genes is a widespread evolutionary procedure for the acquisition of this phenotype. Current information in the field supports the idea that most (if not all) genes acquired by horizontal gene transfer by bacterial pathogens and contributing to their virulence potential or to antibiotic resistance originate in environmental, not human-pathogenic, microorganisms. Herein I discuss the potential functions that the genes that are dubbed virulence or antibiotic resistance genes may have in their original hosts in nonclinical, natural ecosystems. In addition, I discuss the potential bottlenecks modulating the transfer of virulence and antibiotic resistance determinants and the consequences in terms of speciation of acquiring one or another of both categories of genes. Finally, I propose that exaptation, a process by which a change of function is achieved by a change of habitat and not by changes in the element with the new functionality, is the basis of the evolution of virulence determinants and of antibiotic resistance genes.
TL;DR: A number of exogenous and endogenous factors have an effect on the sophisticated process of bacterial conjugation and are put together in an effort to offer a wide picture and inform research to control plasmid transmission, focusing on Gram-negative bacteria.
Abstract: Conjugative plasmids are the main carriers of transmissible antibiotic resistance (AbR) genes. For that reason, strategies to control plasmid transmission have been proposed as potential solutions to prevent AbR dissemination. Natural mechanisms that bacteria employ as defense barriers against invading genomes, such as restriction-modification or CRISPR-Cas systems, could be exploited to control conjugation. Besides, conjugative plasmids themselves display mechanisms to minimize their associated burden or to compete with related or unrelated plasmids. Thus, FinOP systems, composed of FinO repressor protein and FinP antisense RNA, aid plasmids to regulate their own transfer; exclusion systems avoid conjugative transfer of related plasmids to the same recipient bacteria; and fertility inhibition systems block transmission of unrelated plasmids from the same donor cell. Artificial strategies have also been designed to control bacterial conjugation. For instance, intrabodies against R388 relaxase expressed in recipient cells inhibit plasmid R388 conjugative transfer; pIII protein of bacteriophage M13 inhibits plasmid F transmission by obstructing conjugative pili; and unsaturated fatty acids prevent transfer of clinically relevant plasmids in different hosts, promoting plasmid extinction in bacterial populations. Overall, a number of exogenous and endogenous factors have an effect on the sophisticated process of bacterial conjugation. This review puts them together in an effort to offer a wide picture and inform research to control plasmid transmission, focusing on Gram-negative bacteria.
TL;DR: The goal of this article is to describe how monitoring systems for antimicrobial drug usage in animals are set up and conducted, using examples from specific countries as well as international efforts.
Abstract: Monitoring antimicrobial drug usage in animals at the national and international levels is important for identification and tracking if and how often quantities are used. This information can be used for many purposes, including raising awareness, comparing use patterns across countries, identifying trends over time, integrating with antimicrobial resistance data, conducting risk assessment, and evaluating the effectiveness of measures to manage antimicrobial usage. The goal of this article is to describe how monitoring systems for antimicrobial drug usage in animals are set up and conducted, using examples from specific countries as well as international efforts. Several key figures and variables are used to describe and evaluate antimicrobial consumption in animals, including the amount in kilograms of active ingredient, standardized units (e.g., number of defined daily dose animals, DDDAs) and number of treatments (e.g., number of used daily doses, UDDA). Data can be collected from a variety of sources including pharmaceutical sales, pharmacy dispensing, veterinary prescriptions, and farm records. In many countries, data analysis and reporting at the national level provide statistics on overall quantities used in animals, in some cases by animal species. Antimicrobial consumption data should be contrasted to the respective animal population, for example, the weight of different categories of livestock and slaughtered animals. Several countries have established antimicrobial usage monitoring systems. Most report overall sales data, but some provide usage data to the levels of animal species and production type. At the international level, several organizations (e.g., European Union, World Organization for Animal Health, World Health Organization) have initiatives to support the development of antimicrobial consumption data collection and reporting. However, these initiatives are ongoing and so far lack harmonization, which will be the biggest challenge for the future.
TL;DR: The observation that plasmids of staphylococci often harbor more than one resistance gene points toward coselection and persistence of resistance genes even without direct selective pressure by a specific antimicrobial agent.
Abstract: Antimicrobial resistance among staphylococci of animal origin is based on a wide variety of resistance genes. These genes mediate resistance to many classes of antimicrobial agents approved for use in animals, such as penicillins, cephalosporins, tetracyclines, macrolides, lincosamides, phenicols, aminoglycosides, aminocyclitols, pleuromutilins, and diaminopyrimidines. In addition, numerous mutations have been identified that confer resistance to specific antimicrobial agents, such as ansamycins and fluoroquinolones. The gene products of some of these resistance genes confer resistance to only specific members of a class of antimicrobial agents, whereas others confer resistance to the entire class or even to members of different classes of antimicrobial agents, including agents approved solely for human use. The resistance genes code for all three major resistance mechanisms: enzymatic inactivation, active efflux, and protection/modification/replacement of the cellular target sites of the antimicrobial agents. Mobile genetic elements, in particular plasmids and transposons, play a major role as carriers of antimicrobial resistance genes in animal staphylococci. They facilitate not only the exchange of resistance genes among members of the same and/or different staphylococcal species, but also between staphylococci and other Gram-positive bacteria. The observation that plasmids of staphylococci often harbor more than one resistance gene points toward coselection and persistence of resistance genes even without direct selective pressure by a specific antimicrobial agent. This chapter provides an overview of the resistance genes and resistance-mediating mutations known to occur in staphylococci of animal origin.
TL;DR: This article focuses on prevention of antimicrobial resistance and its complex relationship with treatment efficacy, highlighting key situations where the current antimicrobial drug products, treatment recommendations, and practices may be insufficient to minimize antimicrobial selection.
Abstract: Optimization of antimicrobial treatment is a cornerstone in the fight against antimicrobial resistance. Various national and international authorities and professional veterinary and farming associations have released generic guidelines on prudent antimicrobial use in animals. However, these generic guidelines need to be translated into a set of animal species- and disease-specific practice recommendations. This article focuses on prevention of antimicrobial resistance and its complex relationship with treatment efficacy, highlighting key situations where the current antimicrobial drug products, treatment recommendations, and practices may be insufficient to minimize antimicrobial selection. The authors address this topic using a multidisciplinary approach involving microbiology, pharmacology, clinical medicine, and animal husbandry. In the first part of the article, we define four key targets for implementing the concept of optimal antimicrobial treatment in veterinary practice: (i) reduction of overall antimicrobial consumption, (ii) improved use of diagnostic testing, (iii) prudent use of second-line, critically important antimicrobials, and (iv) optimization of dosage regimens. In the second part, we provided practice recommendations for achieving these four targets, with reference to specific conditions that account for most antimicrobial use in pigs (intestinal and respiratory disease), cattle (respiratory disease and mastitis), dogs and cats (skin, intestinal, genitourinary, and respiratory disease), and horses (upper respiratory disease, neonatal foal care, and surgical infections). Lastly, we present perspectives on the education and research needs for improving antimicrobial use in the future.
TL;DR: The need for more-comprehensive analyses of sRNA evolutionary patterns is highlighted as a means to improve novel sRNA detection, enhance genome annotation, and deepen the understanding of regulatory networks in bacteria.
Abstract: Despite the central role of bacterial noncoding small RNAs (sRNAs) in posttranscriptional regulation, little is understood about their evolution. Here we compile what has been studied to date and trace a life cycle of sRNAs—from their mechanisms of emergence, through processes of change and frequent neofunctionalization, to their loss from bacterial lineages. Because they possess relatively unrestrictive structural requirements, we find that sRNA origins are varied, and include de novo emergence as well as formation from preexisting genetic elements via duplication events and horizontal gene transfer. The need for only partial complementarity to their mRNA targets facilitates apparent rapid change, which also contributes to significant challenges in tracing sRNAs across broad evolutionary distances. We document that recently emerged sRNAs in particular evolve quickly, mirroring dynamics observed in microRNAs, their functional analogs in eukaryotes. Mutations in mRNA-binding regions, transcriptional regulator or sigma factor binding sites, and protein-binding regions are all likely sources of shifting regulatory roles of sRNAs. Finally, using examples from the few evolutionary studies available, we examine cases of sRNA loss and describe how these may be the result of adaptive in addition to neutral processes. We highlight the need for more-comprehensive analyses of sRNA evolutionary patterns as a means to improve novel sRNA detection, enhance genome annotation, and deepen our understanding of regulatory networks in bacteria.
TL;DR: The article discusses the acquisition of diverse resistance genes by the selected Pasteurellaceae members from other Gram-negative or maybe even Gram-positive bacteria, and the susceptibility status of these members still looks rather favorable.
Abstract: Members of the highly heterogeneous family Pasteurellaceae cause a wide variety of diseases in humans and animals. Antimicrobial agents are the most powerful tools to control such infections. However, the acquisition of resistance genes, as well as the development of resistance-mediating mutations, significantly reduces the efficacy of the antimicrobial agents. This article gives a brief description of the role of selected members of the family Pasteurellaceae in animal infections and of the most recent data on the susceptibility status of such members. Moreover, a review of the current knowledge of the genetic basis of resistance to antimicrobial agents is included, with particular reference to resistance to tetracyclines, β-lactam antibiotics, aminoglycosides/aminocyclitols, folate pathway inhibitors, macrolides, lincosamides, phenicols, and quinolones. This article focusses on the genera of veterinary importance for which sufficient data on antimicrobial susceptibility and the detection of resistance genes are currently available (Pasteurella, Mannheimia, Actinobacillus, Haemophilus, and Histophilus). Additionally, the role of plasmids, transposons, and integrative and conjugative elements in the spread of the resistance genes within and beyond the aforementioned genera is highlighted to provide insight into horizontal dissemination, coselection, and persistence of antimicrobial resistance genes. The article discusses the acquisition of diverse resistance genes by the selected Pasteurellaceae members from other Gram-negative or maybe even Gram-positive bacteria. Although the susceptibility status of these members still looks rather favorable, monitoring of their antimicrobial susceptibility is required for early detection of changes in the susceptibility status and the newly acquired/developed resistance mechanisms.
TL;DR: This work reviews the integration of sRNAs into the complex networks of several major envelope stress responses of Gram-negative bacteria, including the RpoE (σE), Cpx, and Rcs regulons, and focuses on Escherichia coli and related bacteria.
Abstract: The ability of bacteria to thrive in diverse habitats and to adapt to ever-changing environmental conditions relies on the rapid and stringent modulation of gene expression It has become evident in the past decade that small regulatory RNAs (sRNAs) are central components of networks controlling the bacterial responses to stress Functioning at the posttranscriptional level, sRNAs base-pair with cognate mRNAs to alter translation, stability, or both to either repress or activate the targeted transcripts; the RNA chaperone Hfq participates in stabilizing sRNAs and in promoting pairing between target and sRNA In particular, sRNAs act at the heart of crucial stress responses, including those dedicated to overcoming membrane damage and oxidative stress, discussed here The bacterial cell envelope is the outermost protective barrier against the environment and thus is constantly monitored and remodeled Here, we review the integration of sRNAs into the complex networks of several major envelope stress responses of Gram-negative bacteria, including the RpoE (σE), Cpx, and Rcs regulons Oxidative stress, caused by bacterial respiratory activity or induced by toxic molecules, can lead to significant damage of cellular components In Escherichia coli and related bacteria, sRNAs also contribute significantly to the function of the RpoS (σS)-dependent general stress response as well as the specific OxyR- and SoxR/S-mediated responses to oxidative damage Their activities in gene regulation and crosstalk to other stress-induced regulons are highlighted