Showing papers in "Future Microbiology in 2010"
TL;DR: The persistence of chronic Pseudomonas aeruginosa lung infections in cystic fibrosis patients is due to biofilm-growing mucoid (alginate-producing) strains, which are the major cause of the lung tissue damage in CF.
Abstract: The persistence of chronic Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) patients is due to biofilm-growing mucoid (alginate-producing) strains. A biofilm is a structured consortium of bacteria, embedded in a self-produced polymer matrix consisting of polysaccharide, protein and DNA. In CF lungs, the polysaccharide alginate is the major part of the P. aeruginosa biofilm matrix. Bacterial biofilms cause chronic infections because they show increased tolerance to antibiotics and resist phagocytosis, as well as other components of the innate and the adaptive immune system. As a consequence, a pronounced antibody response develops, leading to immune complex-mediated chronic inflammation, dominated by polymorphonuclear leukocytes. The chronic inflammation is the major cause of the lung tissue damage in CF. Biofilm growth in CF lungs is associated with an increased frequency of mutations, slow growth and adaptation of the bacteria to the conditions in the lungs, and to antibiotic therapy. Low bacterial metabolic activity and increase of doubling times of the bacterial cells in CF lungs are responsible for some of the tolerance to antibiotics. Conventional resistance mechanisms, such as chromosomal β-lactamase, upregulated efflux pumps, and mutations of antibiotic target molecules in the bacteria, also contribute to the survival of P. aeruginosa biofilms. Biofilms can be prevented by early aggressive antibiotic prophylaxis or therapy, and they can be treated by chronic suppressive therapy.
588 citations
TL;DR: The present knowledge on S. suis infection in humans is critically reviewed, the hypotheses that may explain the 2005 outbreak are discussed and the repercussion of such an episode on the scientific community is discussed.
Abstract: Infections caused by Streptococcus suis are considered a global and an economical problem in the swine industry. Moreover, S. suis is an agent of zoonosis that afflicts people in close contact with infected pigs or pork-derived products. Although sporadic cases of S. suis infections in humans (mainly meningitis) have been reported during the last 40 years, a large outbreak due to this pathogen emerged in the summer of 2005 in China. The severity of the infection in humans during the outbreak, such as a shorter incubation time, more rapid disease progression and higher rate of mortality, attracted a lot of attention from the scientific community and the general press. In fact, the number of publications on S. suis (including the number of reported human cases) has significantly increased during recent years. In this article we critically review the present knowledge on S. suis infection in humans, we discuss the hypotheses that may explain the 2005 outbreak and the repercussion of such an episode on the scientific community.
378 citations
TL;DR: It is hypothesized that studies focused on understanding the biological function of each step in staphylococcal biofilm formation will yield new treatment modalities to treat these recalcitrant infections.
Abstract: Staphylococcus epidermidis is a highly significant nosocomial pathogen mediating infections primarily associated with indwelling biomaterials (e.g., catheters and prostheses). In contrast to Staphylococcus aureus, virulence properties associated with S. epidermidis are few and biofilm formation is the defining virulence factor associated with disease, as demonstrated by animal models of biomaterial-related infections. However, other virulence factors, such as phenol-soluble modulins and poly-γ-DL-glutamic acid, have been recently recognized that thwart innate immune system mechanisms. Formation of S. epidermidis biofilm is typically considered a four-step process consisting of adherence, accumulation, maturation and dispersal. This article will discuss recent advances in the study of these four steps, including accumulation, which can be either polysaccharide or protein mediated. It is hypothesized that studies focused on understanding the biological function of each step in staphylococcal biofilm formation will yield new treatment modalities to treat these recalcitrant infections.
369 citations
TL;DR: The application of MALDI-TOF-MS tools in routine clinical diagnosis, including the identification of bacteria at the species, subspecies, strain and lineage levels, and the Identification of bacterial toxins and antibiotic-resistance type is reviewed.
Abstract: MALDI-TOF-mass spectrometry (MS) has been successfully adapted for the routine identification of microorganisms in clinical microbiology laboratories in the past 10 years. This revolutionary technique allows for easier and faster diagnosis of human pathogens than conventional phenotypic and molecular identification methods, with unquestionable reliability and cost–effectiveness. This article will review the application of MALDI-TOF-MS tools in routine clinical diagnosis, including the identification of bacteria at the species, subspecies, strain and lineage levels, and the identification of bacterial toxins and antibiotic-resistance type. We will also discuss the application of MALDI-TOF-MS tools in the identification of Archaea, eukaryotes and viruses. Pathogenic identification from colony-cultured, blood-cultured, urine and environmental samples is also reviewed.
330 citations
TL;DR: This article will address the animal models of acute and chronic leptospire infections, and the recent developments in the genetic manipulation of the bacteria, which facilitate the identification of virulence factors involved in pathogenesis and the assessment of their potential values in the control and prevention ofLeptospirosis.
Abstract: Leptospirosis, the most widespread zoonosis in the world, is an emerging public health problem, particularly in large urban centers of developing countries. Several pathogenic species of the genus Leptospira can cause a wide range of clinical manifestations, from a mild, flu-like illness to a severe disease form characterized by multiorgan system complications leading to death. However, the mechanisms of pathogenesis of Leptospira are largely unknown. This article will address the animal models of acute and chronic leptospire infections, and the recent developments in the genetic manipulation of the bacteria, which facilitate the identification of virulence factors involved in pathogenesis and the assessment of their potential values in the control and prevention of leptospirosis.
296 citations
TL;DR: Streptococcus mutans has been the focus of rigorous research efforts due to its involvement in caries initiation and progression and its remarkable ability to withstand the acid onslaught by utilizing a wide variety of highly evolved acid-tolerance mechanisms.
Abstract: Since its discovery in 1924 by J Clarke, Streptococcus mutans has been the focus of rigorous research efforts due to its involvement in caries initiation and progression. Its ability to ferment a range of dietary carbohydrates can rapidly drop the external environmental pH, thereby making dental plaque inhabitable to many competing species and can ultimately lead to tooth decay. Acid production by this oral pathogen would prove suicidal if not for its remarkable ability to withstand the acid onslaught by utilizing a wide variety of highly evolved acid-tolerance mechanisms. The elucidation of these mechanisms will be discussed, serving as the focus of this review.
186 citations
TL;DR: Recent data from the research literature that enhance understanding of the nature of these two toxins, their role in the pathogenesis of B. pertussis infection and disease, particularly in modulating host immune responses, and their use as tools for other areas of research will be outlined.
Abstract: Pertussis toxin and adenylate cyclase toxin are two important virulence factors of Bordetella pertussis, the bacterial cause of the respiratory disease pertussis or whooping cough. In addition to studies on the structure, function and role in pathogenesis of these two toxins, they are both used as cell biology tools for a variety of applications owing to their ability to enter mammalian cells, perform enzymatic activities and modify cell signaling events. In this article, recent data from the research literature that enhance our understanding of the nature of these two toxins, their role in the pathogenesis of B. pertussis infection and disease, particularly in modulating host immune responses, and their use as tools for other areas of research will be outlined.
183 citations
TL;DR: Although antibiotic resistance has not emerged in chlamydiae pathogenic to humans, several lines of evidence suggest they are capable of expressing significant resistant phenotypes and the adept ability of chlam Lydiae to evolve to antibiotic resistance in vitro is demonstrated.
Abstract: There are few documented reports of antibiotic resistance in Chlamydia and no examples of natural and stable antibiotic resistance in strains collected from humans. While there are several reports of clinical isolates exhibiting resistance to antibiotics, these strains either lost their resistance phenotype in vitro, or lost viability altogether. Differences in procedures for chlamydial culture in the laboratory, low recovery rates of clinical isolates and the unknown significance of heterotypic resistance observed in culture may interfere with the recognition and interpretation of antibiotic resistance. Although antibiotic resistance has not emerged in chlamydiae pathogenic to humans, several lines of evidence suggest they are capable of expressing significant resistant phenotypes. The adept ability of chlamydiae to evolve to antibiotic resistance in vitro is demonstrated by contemporary examples of mutagenesis, recombination and genetic transformation. The isolation of tetracycline-resistant Chlamydia suis strains from pigs also emphasizes their adaptive ability to acquire antibiotic resistance genes when exposed to significant selective pressure.
178 citations
TL;DR: Current and future studies will determine the role of TMC207 in a shortened treatment regimen for drug-sensitive TB, a more effective and better-tolerated regimen for MDR-TB, the treatment of latent TB infection, and intermittent-TB treatment regimens.
Abstract: Disease caused by Mycobacterium tuberculosis continues as a global epidemic: over 2 billion people harbor latent TB infection, and more than 9 million new TB cases, of whom 500,000 are multidrug-resistant (MDR), and nearly 2 million deaths are estimated to occur each year. New drugs are required to shorten treatment duration of drug-sensitive TB and for the treatment of MDR-TB. TMC207 is a first-in-class diarylquinoline compound with a novel mechanism of action, the inhibition of bacterial ATP synthase, and potent activity against drug-sensitive and drug-resistant TB. It has bactericidal and sterilizing activity against M. tuberculosis and other mycobacterial species, but little activity against other bacteria. In a Phase II efficacy study conducted in patients with MDR-TB taking TMC207 plus a standard background regimen, the drug appeared to be safe and well tolerated, and showed significant efficacy after 2 months of treatment with conversion rates of sputum culture of 48% (vs 9% in the placebo group). Given the product development partnership between Tibotec and the TB Alliance, the strategies of using TMC207 in shorter first-line regimens or using it in second-line regimens for drug-resistant M. tuberculosis infections are both being pursued. No clinical data of TMC207 in TB patients with HIV coinfection have been published; drug-drug interaction studies with antiretrovirals are being conducted. Finally, the remarkable sterilizing capacity of TMC207 also makes it an attractive drug in the strategy of TB elimination. Current and future studies will determine the role of TMC207 in a shortened treatment regimen for drug-sensitive TB, a more effective and better-tolerated regimen for MDR-TB, the treatment of latent TB infection, and intermittent-TB treatment regimens.
177 citations
TL;DR: The innate mechanisms that host cells have evolved to resist virus infection are reviewed, and the plethora of strategies that influenza viruses have developed in order to counteract such powerful defences are outlined.
Abstract: Influenza viruses are globally important human respiratory pathogens. These viruses cause seasonal epidemics and occasional worldwide pandemics, both of which can vary significantly in disease severity. The virulence of a particular influenza virus strain is partly determined by its success in circumventing the host immune response. This article briefly reviews the innate mechanisms that host cells have evolved to resist virus infection, and outlines the plethora of strategies that influenza viruses have developed in order to counteract such powerful defences. The molecular details of this virus-host interplay are summarized, and the ways in which research in this area is being applied to the rational design of protective vaccines and novel antivirals are discussed.
161 citations
TL;DR: The mechanisms that influence transfer potential in conjugative plasmids and ICEs, particularly those of the IncF incompatibility group, are focused on.
Abstract: Conjugative plasmids are involved in the dissemination of important traits such as antibiotic resistance, virulence determinants and metabolic pathways involved in adapting to environmental niches, a process termed horizontal or lateral gene transfer. Conjugation is the process of transferring DNA from a donor to a recipient cell with the establishment of the incoming DNA and its cargo of genetic traits within the transconjugant. Conjugation is mediated by self-transmissible plasmids as well as phage-like sequences that have been integrated into the bacterial chromosome, such as integrative and conjugative elements (ICEs) that now include conjugative transposons. Both conjugative plasmids and ICEs can mediate the transfer of mobilizable elements by sharing their conjugative machinery. Conjugation can either be induced, usually by small molecules or peptides or by excision of the ICE from the host chromosome, or it can be tightly regulated by plasmid- and host-encoded factors. The transfer potential of these transfer regions depends on the integration of many signals in response to environmental and physiological cues. This review will focus on the mechanisms that influence transfer potential in these systems, particularly those of the IncF incompatibility group.
TL;DR: Understanding HPV mRNA expression and its regulation in the different diseases associated with infection may lead to development of novel diagnostic approaches and will reveal key viral and cellular targets forDevelopment of novel antiviral therapies.
Abstract: Human papillomaviruses (HPVs) cause diseases ranging from benign warts to invasive tumors. A subset of these viruses termed 'high risk' infect the cervix where persistent infection can lead to cervical cancer. Although many HPV genomes have been sequenced, knowledge of virus gene expression and its regulation is still incomplete. This is due in part to the lack, until recently, of suitable systems for virus propagation in the laboratory. HPV gene expression is polycistronic initiating from multiple promoters. Gene regulation occurs at transcriptional, but particularly post-transcriptional levels, including RNA processing, nuclear export, mRNA stability and translation. A close association between the virus replication cycle and epithelial differentiation adds a further layer of complexity. Understanding HPV mRNA expression and its regulation in the different diseases associated with infection may lead to development of novel diagnostic approaches and will reveal key viral and cellular targets for development of novel antiviral therapies.
TL;DR: Metagenomics-based tools, such as microarrays and high-throughput sequencing, have the potential to detect the full spectrum of viruses, including those present in low numbers.
Abstract: Modern laboratory techniques for the detection of novel human viruses are greatly needed as physicians and epidemiologists increasingly deal with infectious diseases caused by new or previously unrecognized pathogens. There are many clinical syndromes in which viruses are suspected to play a role, but for which traditional microbiology techniques routinely fail in uncovering the etiologic agent. In addition, new viruses continue to challenge the human population owing to the encroachment of human settlements into animal and livestock habitats, globalization, climate change, growing numbers of immunocompromised people and bioterrorism. Metagenomics-based tools, such as microarrays and high-throughput sequencing are ideal for responding to these challenges. Pan-viral microarrays, containing representative sequences from all known viruses, have been used to detect novel and distantly-related variants of known viruses. Sequencing-based methods have also been successfully employed to detect novel viruses and h...
TL;DR: Antibiotic resistance in several Salmonella enterica serovar Typhimurium DT104 isolates that cause gastrointestinal disease in humans is due to a set of related genomic islands carrying a class 1 integron, which carries the resistance genes.
Abstract: Antibiotic resistance in several Salmonella enterica serovars that cause gastrointestinal disease in humans is due to a set of related genomic islands carrying a class 1 integron, which carries the resistance genes. Salmonella genomic island 1 (SGI1), the first island of this type, was found in S. enterica serovar Typhimurium DT104 isolates, which are resistant to ampicillin, chloramphenicol, florfenicol, streptomycin, spectinomycin, sulfonamides and tetracycline. Several Salmonella serovars and Proteus mirablis have since been shown to harbor SGI1 or related islands carrying various sets of resistance genes and some distinct groups have emerged. SGI1 is an integrative mobilizable element and can be transferred experimentally into Escherichia coli. However, within serovars, isolates recovered from different parts of the world appear to be clonal, indicating that SGI1 movement may be rare. Potential reservoirs in food-producing animals or in ornamental fish have been identified for some serovars.
TL;DR: A model suggesting an important role for this signaling pathway in the temporal control of virulence in Salmonella enterica and biofilm formation in Escherichia coli is presented.
Abstract: The Rcs phosphorelay is a complex signaling pathway found in many, but not all, members of the Enterobacteriaceae. The complexity of this pathway is due to the direct involvement of three proteins (RcsC, RcsD and RcsB) in the phosphorelay and the presence of multiple accessory proteins with important roles in modulating the inputs and outputs associated with this signaling pathway. This article will discuss the various inputs and outputs associated with the Rcs phosphorelay and also present a model suggesting an important role for this signaling pathway in the temporal control of virulence in Salmonella enterica and biofilm formation in Escherichia coli.
TL;DR: Recent advances in understanding the architectures of the T4P and T2S systems, and the organization of their inner and outer membrane components are highlighted.
Abstract: Motility and protein secretion are key processes contributing to bacterial virulence. A wealth of phylogenetic, biochemical and structural evidence support the hypothesis that the widely distributed type IV pilus (T4P) system, involved in twitching motility, and the type II secretion (T2S) system, involved in exoprotein release, are descended from a common progenitor. Both are composed of dedicated but dynamic assemblages, which have been proposed to function through alternate polymerization and depolymerization or degradation of pilin-like subunits. While ongoing studies aimed at understanding the details of assembly and function of these systems are leading to new insights, there are still large knowledge gaps with respect to several fundamental aspects of their biology, including the localization and stoichiometry of critical assembly components, and the nature of their interactions. This article highlights recent advances in understanding the architectures of the T4P and T2S systems, and the organization of their inner and outer membrane components. As structural data accumulates, it is becoming increasingly apparent that even components with little-to-no sequence similarity have similar folds, further supporting the idea that both systems function by a similar mechanism.
TL;DR: This phenomenon provides these wall-less pathogens with a means to escape the host immune response and to modulate surface accessibility by masking and unmasking stably expressed components that are essential in host interaction and survival.
Abstract: With their reduced genome bound by a single membrane, bacteria of the Mycoplasma species represent some of the simplest autonomous life forms. Yet, these minute prokaryotes are able to establish persistent infection in a wide range of hosts, even in the presence of a specific immune response. Clues to their success in host adaptation and survival reside, in part, in a number of gene families that are affected by frequent, stochastic genotypic changes. These genetic events alter the expression, the size and the antigenic structure of abundant surface proteins, thereby creating highly versatile and dynamic surfaces within a clonal population. This phenomenon provides these wall-less pathogens with a means to escape the host immune response and to modulate surface accessibility by masking and unmasking stably expressed components that are essential in host interaction and survival.
TL;DR: Molecular typing of C. albicans strains shows geographical evolutionary associations but these have become partially blurred, probably as a result of extensive human travel.
Abstract: Candida albicans, a diploid yeast commensal and opportunist pathogen, has evolved unusual mechanisms for maintenance of genetic diversity in the absence of a complete sexual cycle. These include chromosomal polymorphisms, mitotic recombination events, and gains and losses of heterozygosity, superimposed on a fundamentally clonal mode of reproduction. Molecular typing of C. albicans strains shows geographical evolutionary associations but these have become partially blurred, probably as a result of extensive human travel. Individual patients usually carry a single C. albicans strain type, but this may undergo microvariation leading to detection of mixtures of closely related types. Associations have been found between clade 1, the most common multilocus sequence typing cluster of related C. albicans strains, and resistance to flucytosine and terbinafine. There are also clade-related associations with lengths of tandem repeats in some cell-surface proteins, but not with virulence or type of infection.
TL;DR: The contribution of secretory immunoglobulin A (SIgA) antibodies in the defense of mucosal epithelia plays an important role in preventing pathogen adhesion to host cells, therefore blocking dissemination and further infection as discussed by the authors.
Abstract: The contribution of secretory immunoglobulin A (SIgA) antibodies in the defense of mucosal epithelia plays an important role in preventing pathogen adhesion to host cells, therefore blocking dissemination and further infection. This mechanism, referred to as immune exclusion, represents the dominant mode of action of the antibody. However, SIgA antibodies combine multiple facets, which together confer properties extending from intracellular and serosal neutralization of antigens, activation of non-inflammatory pathways and homeostatic control of the endogenous microbiota. The sum of these features suggests that future opportunities for transvlational application from research-based knowledge to clinics include the mucosal delivery of bioactive antibodies capable of preserving immunoreactivity in the lung, gastrointestinal tract, the genito–urinary tract for the treatment of infections. This article covers topics dealing with the structure of SIgA, the dissection of its mode of action in epithelia lining d...
TL;DR: The current understanding of the protein export systems of M. tuberculosis is discussed and the potential of these pathways to be novel targets for tuberculosis drugs is considered.
Abstract: Protein export is essential in all bacteria and many bacterial pathogens depend on specialized protein export systems for virulence. In Mycobacterium tuberculosis, the etiological agent of the disease tuberculosis, the conserved general secretion (Sec) and twin-arginine translocation (Tat) pathways perform the bulk of protein export and are both essential. M. tuberculosis also has specialized export pathways that transport specific subsets of proteins. One such pathway is the accessory SecA2 system, which is important for M. tuberculosis virulence. There are also specialized ESX export systems that function in virulence (ESX-1) or essential physiologic processes (ESX-3). The increasing prevalence of drug-resistant M. tuberculosis strains makes the development of novel drugs for tuberculosis an urgent priority. In this article, we discuss our current understanding of the protein export systems of M. tuberculosis and consider the potential of these pathways to be novel targets for tuberculosis drugs.
TL;DR: H. pylori isolates after two eradication failures are often resistant to both metronidazole and clarithromycin, and the alternative candidates for third-line therapy are quinolones, tetracycline, rifabutin and furazolidone; high-dose PPI/amoxicillin therapy might also be promising.
Abstract: Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcers and gastric cancer. H. pylori eradication has been shown to have a prophylactic effect against gastric cancer. According to several international guidelines, the first-line therapy for treating H. pylori infection consists of a proton pump inhibitor (PPI) or ranitidine bismuth citrate, with any two antibiotics among amoxicillin, clarithromycin and metronidazole, given for 7-14 days. However, even with these recommended regimens, H. pylori eradication failure is still seen in more than 20% of patients. The failure rate for first-line therapy may be higher in actual clinical practice, owing to the indiscriminate use of antibiotics. The recommended second-line therapy is a quadruple regimen composed of tetracycline, metronidazole, a bismuth salt and a PPI. The combination of PPI-amoxicillin-levofloxacin is a good option as second-line therapy. In the case of failure of second-line therapy, the patients should be evaluated using a case-by-case approach. European guidelines recommend culture before the selection of a third-line treatment based on the microbial antibiotic sensitivity. H. pylori isolates after two eradication failures are often resistant to both metronidazole and clarithromycin. The alternative candidates for third-line therapy are quinolones, tetracycline, rifabutin and furazolidone; high-dose PPI/amoxicillin therapy might also be promising.
TL;DR: Recent progress in tackling the problem of parasite resistance is summarized and the underlying molecular mechanisms that confer resistance to current antimalarial agents as far as they are known are discussed, understanding of which should assist in the rational development of new drugs and the more effective deployment of older ones.
Abstract: Malaria represents one of the most serious threats to human health worldwide, and preventing and curing this parasitic disease still depends predominantly on the administration of a small number of drugs whose efficacy is continually threatened and eroded by the emergence of drug-resistant parasite populations. This has an enormous impact on the mortality and morbidity resulting from malaria infection, especially in sub-Saharan Africa, where the lethal human parasite species Plasmodium falciparum accounts for approximately 90% of deaths recorded globally. Successful treatment of uncomplicated malaria is now highly dependent on artemisinin-based combination therapies. However, the first cases of artemisinin-resistant field isolates have been reported recently and potential replacement antimalarials are only in the developmental stages. Here, we summarize recent progress in tackling the problem of parasite resistance and discuss the underlying molecular mechanisms that confer resistance to current antimalarial agents as far as they are known, understanding of which should assist in the rational development of new drugs and the more effective deployment of older ones.
TL;DR: The ability of L. salivarius to inhibit pathogens and tolerate host antimicrobial defenses demonstrates the adaptation of this species to the gastrointestinal niche.
Abstract: Lactobacillus salivarius has been frequently isolated from the mammalian digestive tract and has been studied as a candidate probiotic. Research to date has described the immunomodulatory properties of the species in cell-lines, mice, rats and humans for the alleviation of intestinal disease and the promotion of host well-being. The ability of L. salivarius to inhibit pathogens and tolerate host antimicrobial defenses demonstrates the adaptation of this species to the gastrointestinal niche. L. salivarius is the best characterized of 25 species in the L. salivarius clade of the genus Lactobacillus. Several other species of this clade are candidate probiotics; however, their probiotic potential has not yet been exploited. This review summarizes the research defining the probiotic nature of L. salivarius, by focusing in particular on L. salivarius UCC118 as a representative strain. The emergent research detailing the probiotic potential of other species in this phylogenetic clade will also be discussed.
TL;DR: The lessons learned from the genomics era are summarized and discovery strategies resulting from that knowledge are described including anti-virulence strategies and immunotherapeutic approaches.
Abstract: During the last decade the field of antibacterial drug discovery has changed in many aspects including bacterial organisms of primary interest, discovery strategies applied and pharmaceutical companies involved. Target-based high-throughput screening had been disappointingly unsuccessful for antibiotic research. Understanding of this lack of success has increased substantially and the lessons learned refer to characteristics of targets, screening libraries and screening strategies. The 'genomics' approach was replaced by a diverse array of discovery strategies, for example, searching for new natural product leads among previously abandoned compounds or new microbial sources, screening for synthetic inhibitors by targeted approaches including structure-based design and analyses of focused libraries and designing resistance-breaking properties into antibiotics of established classes. Furthermore, alternative treatment options are being pursued including anti-virulence strategies and immunotherapeutic approaches. This article summarizes the lessons learned from the genomics era and describes discovery strategies resulting from that knowledge.
TL;DR: Recent molecular research performed on Pseudomonas phages is summarized by reviewing findings on individual phage genera by focusing on emerging studies in coevolutionary and in therapeutic settings.
Abstract: Pseudomonas species and their bacteriophages have been studied intensely since the beginning of the 20th century, due to their ubiquitous nature, and medical and ecological importance. Here, we summarize recent molecular research performed on Pseudomonas phages by reviewing findings on individual phage genera. While large phage collections are stored and characterized worldwide, the limits of their genomic diversity are becoming more and more apparent. Although this article emphasizes the biological background and molecular characteristics of these phages, special attention is given to emerging studies in coevolutionary and in therapeutic settings.
TL;DR: The mechanisms by which C. neoformans can alter adaptive host responses, especially cell-mediated immunity, which is required for clearance of this microbe are described.
Abstract: Cryptococcus neoformans is an environmental yeast that is a leading cause of fatal mycosis in AIDS patients and a major cause of meningoencephalitis and CNS-related mortality around the globe. Although C. neoformans infection is mostly a manifestation of immune deficiency, up to 25% of cases reported in the USA occur in patients without recognizable immune defects, indicating that C. neoformans can develop mechanisms that allow it to evade immune defenses and persist in noncompromised hosts. This article discusses mechanisms and routes of infection and the most important elements of host response as well as the mechanisms that promote cryptococcal survival within the host. Metabolic adaptation to physiological host conditions and the mechanisms limiting immune recognition, interfering with phagocytosis and extending intracellular survival of C. neoformans are highlighted. We describe the mechanisms by which C. neoformans can alter adaptive host responses, especially cell-mediated immunity, which is required for clearance of this microbe. We also review cryptococcal strategies of survival in the CNS and briefly discuss adaptations developing in response to medical treatment.
TL;DR: Evidence that Shiga toxins induce apoptosis of epithelial, endothelial, leukocytic, lymphoid and neuronal cells is presented and signaling mechanisms that are shared among different cell types are reviewed.
Abstract: Shiga toxins comprise a family of structurally and functionally related protein toxins expressed by Shigella dysenteriae serotype 1 and multiple serotypes of Escherichia coli. While the capacity of Shiga toxins to inhibit protein synthesis by catalytic inactivation of eukaryotic ribosomes has been well described, it is also apparent that Shiga toxins trigger apoptosis in many cell types. This review presents evidence that Shiga toxins induce apoptosis of epithelial, endothelial, leukocytic, lymphoid and neuronal cells. Apoptotic signaling pathways activated by the toxins are reviewed with an emphasis on signaling mechanisms that are shared among different cell types. Data suggesting that Shiga toxins induce apoptosis through the endoplasmic reticulum stress response and clinical evidence demonstrating apoptosis in humans infected with Shiga toxin-producing bacteria are briefly discussed. The potential for use of Shiga toxins to induce apoptosis in cancer cells is briefly reviewed.
TL;DR: This review focuses on recent advances and future prospects in the understanding of human immune responses to Cryptosporidium infection.
Abstract: Immune responses play a critical role in protection from, and resolution of, cryptosporidiosis. However, the nature of these responses, particularly in humans, is not completely understood. Both innate and adaptive immune responses are important. Innate immune responses may be mediated by Toll-like receptor pathways, antimicrobial peptides, prostaglandins, mannose-binding lectin, cytokines and chemokines. Cell-mediated responses, particularly those involving CD4+ T cells and IFN-γ play a dominant role. Mucosal antibody responses may also be involved. Proteins mediating attachment and invasion may serve as putative protective antigens. Further knowledge of human immune responses in cryptosporidiosis is essential in order to develop targeted prophylactic and therapeutic interventions. This review focuses on recent advances and future prospects in the understanding of human immune responses to Cryptosporidium infection.
TL;DR: A number of scientists are attempting to reconcile new molecular data describing the phylogenetic relationship between Brucella organisms and a broader family of organisms with widely variant phenotypes that include human virulence and host range against a backdrop of strict regulatory requirements that fail to recognize significant differences between organisms with similar nomenclature.
Abstract: Taxonomy and nomenclature represent man-made systems designed to enhance understanding of the relationship between organisms by comparison of discrete sets of properties. Initial efforts at bacterial taxonomy were flawed as a result of the previous use of nonsystematic approaches including common names resulting in confusing and inaccurate nomenclature. A decision was made to start afresh with bacterial nomenclature and to avoid the hazards experienced in the taxonomic classification of higher organisms. This was achieved by developing new rules designed to simplify classification and avoid unnecessary and confusing changes. This article reviews the work of a number of scientists attempting to reconcile new molecular data describing the phylogenetic relationship between Brucella organisms and a broader family of organisms with widely variant phenotypes that include human virulence and host range against a backdrop of strict regulatory requirements that fail to recognize significant differences between organisms with similar nomenclature.
TL;DR: A particular strain of M. abscessus ssp.
Abstract: Aim: Our aim is to investigate if the clusters of postsurgical mycobacterial infections, reported between 2004 and 2008 in seven geographically distant states in Brazil, were caused by a single mycobacterial strain. Materials & methods: Available information from 929 surgical patients was obtained from local health authorities. A total of 152 isolates from surgical patients were identified by PCR restriction enzyme analysis of the hsp65 gene (PRA-hsp65) and sequencing of the rpoB gene. Isolates were typed by pulsed-field gel electrophoresis (PFGE) using two restriction enzymes, DraI and AseI. A total of 15 isolates not related to surgical cases were analyzed for comparison. Results: All isolates were identified as Mycobacterium abscessus ssp. massiliense. Isolates from surgical patients and one sputum isolate grouped in a single PFGE cluster, composed of two closely related patterns, with one band difference. A total of 14 other isolates unrelated to surgical cases showed distinctive PFGE patterns. Conclu...