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Showing papers in "Fems Microbiology Reviews in 2008"


Journal ArticleDOI
TL;DR: In several species examined, the fine structure of the peptidoglycan significantly varies with the growth conditions, and the different models for the architecture are discussed with respect to structural and physical parameters.
Abstract: The peptidoglycan (murein) sacculus is a unique and essential structural element in the cell wall of most bacteria. Made of glycan strands cross-linked by short peptides, the sacculus forms a closed, bag-shaped structure surrounding the cytoplasmic membrane. There is a high diversity in the composition and sequence of the peptides in the peptidoglycan from different species. Furthermore, in several species examined, the fine structure of the peptidoglycan significantly varies with the growth conditions. Limited number of biophysical data on the thickness, elasticity and porosity of peptidoglycan are available. The different models for the architecture of peptidoglycan are discussed with respect to structural and physical parameters.

1,876 citations


Journal ArticleDOI
TL;DR: The hologenome theory of evolution considers the holobiont (the animal or plant with all of its associated microorganisms) as a unit of selection in evolution and fits within the framework of the 'superorganism' proposed by Wilson and Sober.
Abstract: We present here the hologenome theory of evolution, which considers the holobiont (the animal or plant with all of its associated microorganisms) as a unit of selection in evolution. The hologenome is defined as the sum of the genetic information of the host and its microbiota. The theory is based on four generalizations: (1) All animals and plants establish symbiotic relationships with microorganisms. (2) Symbiotic microorganisms are transmitted between generations. (3) The association between host and symbionts affects the fitness of the holobiont within its environment. (4) Variation in the hologenome can be brought about by changes in either the host or the microbiota genomes; under environmental stress, the symbiotic microbial community can change rapidly. These points taken together suggest that the genetic wealth of diverse microbial symbionts can play an important role both in adaptation and in evolution of higher organisms. During periods of rapid changes in the environment, the diverse microbial symbiont community can aid the holobiont in surviving, multiplying and buying the time necessary for the host genome to evolve. The distinguishing feature of the hologenome theory is that it considers all of the diverse microbiota associated with the animal or the plant as part of the evolving holobiont. Thus, the hologenome theory fits within the framework of the 'superorganism' proposed by Wilson and Sober.

1,270 citations


Journal ArticleDOI
TL;DR: An overview of the content in PBPs of some bacteria is provided with an emphasis on comparing the biochemical properties of homologous PBPs (orthologues) belonging to different bacteria.
Abstract: Penicillin-binding proteins (PBPs) have been scrutinized for over 40 years. Recent structural information on PBPs together with the ongoing long-term biochemical experimental investigations, and results from more recent techniques such as protein localization by green fluorescent protein-fusion immunofluorescence or double-hybrid assay, have brought our understanding of the last stages of the peptidoglycan biosynthesis to an outstanding level that allows a broad outlook on the properties of these enzymes. Details are emerging regarding the interaction between the peptidoglycan-synthesizing PBPs and the peptidoglycan, their mesh net-like product that surrounds and protects bacteria. This review focuses on the detailed structure of PBPs and their implication in peptidoglycan synthesis, maturation and recycling. An overview of the content in PBPs of some bacteria is provided with an emphasis on comparing the biochemical properties of homologous PBPs (orthologues) belonging to different bacteria.

1,104 citations


Journal ArticleDOI
TL;DR: The toxins associated with foodborne diseases frequently caused by B. cereus are reviewed, and recent findings regarding the associated toxins are discussed, as well as the present knowledge on virulence regulation.
Abstract: Bacillus cereus is widespread in nature and frequently isolated from soil and growing plants, but it is also well adapted for growth in the intestinal tract of insects and mammals. From these habitats it is easily spread to foods, where it may cause an emetic or a diarrhoeal type of food-associated illness that is becoming increasingly important in the industrialized world. The emetic disease is a food intoxication caused by cereulide, a small ring-formed dodecadepsipeptide. Similar to the virulence determinants that distinguish Bacillus thuringiensis and Bacillus anthracis from B. cereus, the genetic determinants of cereulide are plasmid-borne. The diarrhoeal syndrome of B. cereus is an infection caused by vegetative cells, ingested as viable cells or spores, thought to produce protein enterotoxins in the small intestine. Three pore-forming cytotoxins have been associated with diarrhoeal disease: haemolysin BL (Hbl), nonhaemolytic enterotoxin (Nhe) and cytotoxin K. Hbl and Nhe are homologous three-component toxins, which appear to be related to the monooligomeric toxin cytolysin A found in Escherichia coli. This review will focus on the toxins associated with foodborne diseases frequently caused by B. cereus. The disease characteristics are described, and recent findings regarding the associated toxins are discussed, as well as the present knowledge on virulence regulation.

1,074 citations


Journal ArticleDOI
TL;DR: The current view on the regulation of autolysins and on the role of cytoplasm hydrolases in peptidoglycan recycling and induction of beta-lactamase is reviewed.
Abstract: Most bacteria have multiple peptidoglycan hydrolases capable of cleaving covalent bonds in peptidoglycan sacculi or its fragments. An overview of the different classes of peptidoglycan hydrolases and their cleavage sites is provided. The physiological functions of these enzymes include the regulation of cell wall growth, the turnover of peptidoglycan during growth, the separation of daughter cells during cell division and autolysis. Specialized hydrolases enlarge the pores in the peptidoglycan for the assembly of large trans-envelope complexes (pili, flagella, secretion systems), or they specifically cleave peptidoglycan during sporulation or spore germination. Moreover, peptidoglycan hydrolases are involved in lysis phenomena such as fratricide or developmental lysis occurring in bacterial populations. We will also review the current view on the regulation of autolysins and on the role of cytoplasm hydrolases in peptidoglycan recycling and induction of β-lactamase.

785 citations


Journal ArticleDOI
TL;DR: The efficiency and regulation of cellulose degradation differs among wood-rotting, litter-decomposing, mycorrhizal or plant pathogenic fungi and yeasts due to the different roles of cellulOSE degradation in the physiology and ecology of the individual groups.
Abstract: Cellulose is the main polymeric component of the plant cell wall, the most abundant polysaccharide on Earth, and an important renewable resource. Basidiomycetous fungi belong to its most potent degraders because many species grow on dead wood or litter, in environment rich in cellulose. Fungal cellulolytic systems differ from the complex cellulolytic systems of bacteria. For the degradation of cellulose, basidiomycetes utilize a set of hydrolytic enzymes typically composed of endoglucanase, cellobiohydrolase and β-glucosidase. In some species, the absence of cellobiohydrolase is substituted by the production of processive endoglucanases combining the properties of both of these enzymes. In addition, systems producing hydroxyl radicals based on cellobiose dehydrogenase, quinone redox cycling or glycopeptide-based Fenton reaction are involved in the degradation of several plant cell wall components, including cellulose. The complete cellulolytic complex used by a single fungal species is typically composed of more than one of the above mechanisms that contribute to the utilization of cellulose as a source of carbon or energy or degrade it to ensure fast substrate colonization. The efficiency and regulation of cellulose degradation differs among wood-rotting, litter-decomposing, mycorrhizal or plant pathogenic fungi and yeasts due to the different roles of cellulose degradation in the physiology and ecology of the individual groups.

724 citations


Journal ArticleDOI
TL;DR: The goal of this review is to provide an outline of the current knowledge of microbial PAH catabolism to facilitate the development of new methods to enhance the bioremediation of PAH-contaminated sites.
Abstract: Polycyclic aromatic hydrocarbons (PAHs) are widespread in various ecosystems and are pollutants of great concern due to their potential toxicity, mutagenicity and carcinogenicity. Because of their hydrophobic nature, most PAHs bind to particulates in soil and sediments, rendering them less available for biological uptake. Microbial degradation represents the major mechanism responsible for the ecological recovery of PAH-contaminated sites. The goal of this review is to provide an outline of the current knowledge of microbial PAH catabolism. In the past decade, the genetic regulation of the pathway involved in naphthalene degradation by different gram-negative and gram-positive bacteria was studied in great detail. Based on both genomic and proteomic data, a deeper understanding of some high-molecular-weight PAH degradation pathways in bacteria was provided. The ability of nonligninolytic and ligninolytic fungi to transform or metabolize PAH pollutants has received considerable attention, and the biochemical principles underlying the degradation of PAHs were examined. In addition, this review summarizes the information known about the biochemical processes that determine the fate of the individual components of PAH mixtures in polluted ecosystems. A deeper understanding of the microorganism-mediated mechanisms of catalysis of PAHs will facilitate the development of new methods to enhance the bioremediation of PAH-contaminated sites.

662 citations


Journal ArticleDOI
TL;DR: This review deals with the cytoplasmic steps of peptidoglycan biosynthesis and the chemical and enzymatic synthesis of the nucleotide precursor substrates that are not commercially available and the search for specific inhibitors that could act as antibacterial compounds.
Abstract: The biosynthesis of bacterial cell wall peptidoglycan is a complex process that involves enzyme reactions that take place in the cytoplasm (synthesis of the nucleotide precursors) and on the inner side (synthesis of lipid-linked intermediates) and outer side (polymerization reactions) of the cytoplasmic membrane. This review deals with the cytoplasmic steps of peptidoglycan biosynthesis, which can be divided into four sets of reactions that lead to the syntheses of (1) UDP-N-acetylglucosamine from fructose 6-phosphate, (2) UDP-N-acetylmuramic acid from UDP-N-acetylglucosamine, (3) UDP-N-acetylmuramyl-pentapeptide from UDP-N-acetylmuramic acid and (4) D-glutamic acid and dipeptide D-alanyl-D-alanine. Recent data concerning the different enzymes involved are presented. Moreover, special attention is given to (1) the chemical and enzymatic synthesis of the nucleotide precursor substrates that are not commercially available and (2) the search for specific inhibitors that could act as antibacterial compounds.

620 citations


Journal ArticleDOI
TL;DR: This review is focused on pathogens that resist by expressing low-affinity targets for these antibiotics, the penicillin-binding proteins (PBPs), and a great variety of strategies have been uncovered.
Abstract: A number of ways and means have evolved to provide resistance to eubacteria challenged by β-lactams. This review is focused on pathogens that resist by expressing low-affinity targets for these antibiotics, the penicillin-binding proteins (PBPs). Even within this narrow focus, a great variety of strategies have been uncovered such as the acquisition of an additional low-affinity PBP, the overexpression of an endogenous low-affinity PBP, the alteration of endogenous PBPs by point mutations or homologous recombination or a combination of the above.

514 citations


Journal ArticleDOI
TL;DR: Divergence-based methods are providing new insights into microbial community structure and function because microorganisms in a community differ dramatically in sequence similarity, which also often correlates with phenotypic similarity in key features such as metabolic capabilities.
Abstract: Diversity measurement is important for understanding community structure and dynamics, but has been particularly challenging for microorganisms. Microbial community characterization using small subunit rRNA (SSU rRNA) gene sequences has revealed an extensive, previously unsuspected diversity that we are only now beginning to understand, especially now that advanced sequencing technologies are producing datasets containing hundreds of thousands of sequences from hundreds of samples. Efforts to quantify microbial diversity often use taxon-based methods that ignore the fact that not all species are equally related, which can therefore obscure important patterns in the data. For example, α-diversity (diversity within communities) is often estimated as the number of species in a community (species richness), and β-diversity (partitioning of diversity among communities) is often based on the number of shared species. Methods for measuring α- and β-diversity that account for different levels of divergence between individuals have recently been more widely applied. These methods are more powerful than taxon-based methods because microorganisms in a community differ dramatically in sequence similarity, which also often correlates with phenotypic similarity in key features such as metabolic capabilities. Consequently, divergence-based methods are providing new insights into microbial community structure and function.

447 citations


Journal ArticleDOI
TL;DR: This review summarizes the current knowledge on the membrane steps leading to the formation of the lipid II intermediate, i.e. the substrate of the polymerization reactions.
Abstract: The biosynthesis of bacterial cell wall peptidoglycan is a complex process involving many different steps taking place in the cytoplasm (synthesis of the nucleotide precursors) and on the inner and outer sides of the cytoplasmic membrane (assembly and polymerization of the disaccharide-peptide monomer unit, respectively). This review summarizes the current knowledge on the membrane steps leading to the formation of the lipid II intermediate, i.e. the substrate of the polymerization reactions. It makes the point on past and recent data that have significantly contributed to the understanding of the biosynthesis of undecaprenyl phosphate, the carrier lipid required for the anchoring of the peptidoglycan hydrophilic units in the membrane, and to the characterization of the MraY and MurG enzymes which catalyze the successive transfers of the N-acetylmuramoyl-peptide and N-acetylglucosamine moieties onto the carrier lipid, respectively. Enzyme inhibitors and antibacterial compounds interfering with these essential metabolic steps and interesting targets are presented.

Journal ArticleDOI
TL;DR: The reductive evolutionary process that has led to the minimal genome of M. pneumoniae suggests that it exists as a highly specialized parasitic bacterium capable of residing in an intracellular state within the respiratory tissues, occasionally emerging to produce symptoms.
Abstract: Since its initial description in the 1940s and eventual elucidation as a highly evolved pathogenic bacterium, Mycoplasma pneumoniae has come to be recognized as a worldwide cause of primary atypical pneumonia. Beyond its ability to cause severe lower respiratory illness and milder upper respiratory symptoms it has become apparent that a wide array of extrapulmonary infectious and postinfectious events may accompany the infections in humans caused by this organism. Autoimmune disorders and chronic diseases such as asthma and arthritis are increasingly being associated with this mycoplasma, which frequently persists in individuals for prolonged periods. The reductive evolutionary process that has led to the minimal genome of M. pneumoniae suggests that it exists as a highly specialized parasitic bacterium capable of residing in an intracellular state within the respiratory tissues, occasionally emerging to produce symptoms. This review includes discussion of some of the newer aspects of our knowledge on this pathogen, characteristics of clinical infections, how it causes disease, the recent emergence of macrolide resistance, and the status of laboratory diagnostic methods.

Journal ArticleDOI
TL;DR: The Pho regulon is clearly not a simple regulatory circuit for controlling phosphate homeostasis; it is part of a complex network important for both bacterial virulence and stress response.
Abstract: Bacterial pathogens regulate virulence factor gene expression coordinately in response to environmental stimuli, including nutrient starvation. The phosphate (Pho) regulon plays a key role in phosphate homeostasis. It is controlled by the PhoR/PhoB two-component regulatory system. PhoR is an integral membrane signaling histidine kinase that, through an interaction with the ABC-type phosphate-specific transport (Pst) system and a protein called PhoU, somehow senses environmental inorganic phosphate (Pi) levels. Under conditions of Pi limitation (or in the absence of a Pst component or PhoU), PhoR activates its partner response regulator PhoB by phosphorylation, which, in turn, up- or down-regulates target genes. Single-cell profiling of PhoB activation has shown recently that Pho regulon gene expression exhibits a stochastic, ‘all-or-none,’ behavior. Recent studies have also shown that the Pho regulon plays a role in the virulence of several bacteria. Here, we present a comprehensive overview of the role of the Pho regulon in bacterial virulence. The Pho regulon is clearly not a simple regulatory circuit for controlling phosphate homeostasis; it is part of a complex network important for both bacterial virulence and stress response.

Journal ArticleDOI
TL;DR: An overview of plant-associated Burkholderia spp.
Abstract: Both in natural and in managed ecosystems, bacteria are common inhabitants of the phytosphere and the internal tissues of plants. Probably the most diverse and environmentally adaptable plant-associated bacteria belong to the genus Burkholderia. This genus is well-known for its human, animal and plant pathogenic members, including the Burkholderia cepacia complex. However, it also contains species and strains that are beneficial to plants and can be potentially exploited in biotechnological processes. Here we present an overview of plant-associated Burkholderia spp. with special emphasis on beneficial plant-Burkholderia interactions. A discussion of the potential for utilization of stable plant-Burkholderia spp. associations in the development of low-input cropping systems is also provided.

Journal ArticleDOI
TL;DR: This review describes the structure of secondary modifications and of attachment sites of surface polymers in the glycan strands of peptidoglycan and provides an overview of the occurrence of these modifications in various bacterial species.
Abstract: The normal, unmodified glycan strands of bacterial peptidoglycan consist of alternating residues of beta-1,4-linked N-acetylmuramic acid and N-acetylglucosamine. In many species the glycan strands become modified after their insertion into the cell wall. This review describes the structure of secondary modifications and of attachment sites of surface polymers in the glycan strands of peptidoglycan. It also provides an overview of the occurrence of these modifications in various bacterial species. Recently, enzymes responsible for the N-deacetylation, N-glycolylation and O-acetylation of the glycan strands were identified. The presence of these modifications affects the hydrolysis of peptidoglycan and its enlargement during cell growth. Glycan strands are frequently deacetylated and/or O-acetylated in pathogenic species. These alterations affect the recognition of bacteria by host factors, and contribute to the resistance of bacteria to host defence factors such as lysozyme.

Journal ArticleDOI
TL;DR: The range of methods that can be used to assess small phytoplankton diversity are discussed, the species described to date are presented, the existing molecular data obtained on field populations are reviewed, and the promises offered by genomics are looked at.
Abstract: Small cells dominate photosynthetic biomass and primary production in many marine ecosystems. Traditionally, picoplankton refers to cells < or =2 microm. Here we extend the size range of the organisms considered to 3 microm, a threshold often used operationally in field studies. While the prokaryotic component of picophytoplankton is dominated by two genera, Prochlorococcus and Synechococcus, the eukaryotic fraction is much more diverse. Since the discovery of the ubiquitous Micromonas pusilla in the early 1950s, just over 70 species that can be <3 microm have been described. In fact, most algal classes contain such species. Less than a decade ago, culture-independent approaches (in particular, cloning and sequencing, denaturing gradient gel electrophoresis, FISH) have demonstrated that the diversity of eukaryotic picoplankton is much more extensive than could be assumed from described taxa alone. These approaches revealed the importance of certain classes such as the Prasinophyceae but also unearthed novel divisions such as the recently described picobiliphytes. In the last couple of years, the first genomes of photosynthetic picoplankton have become available, providing key information on their physiological capabilities. In this paper, we discuss the range of methods that can be used to assess small phytoplankton diversity, present the species described to date, review the existing molecular data obtained on field populations, and end up by looking at the promises offered by genomics.

Journal ArticleDOI
TL;DR: It seems that nitroreductase genes may be controlled by the MarRA and SoxRS regulatory systems that are involved in responses to several antibiotics and environmental chemical hazards and to specific oxidative stress conditions.
Abstract: Most nitroaromatic compounds are toxic and mutagenic for living organisms, but some microorganisms have developed oxidative or reductive pathways to degrade or transform these compounds. Reductive pathways are based either on the reduction of the aromatic ring by hydride additions or on the reduction of the nitro groups to hydroxylamino and/or amino derivatives. Bacterial nitroreductases are flavoenzymes that catalyze the NAD(P)H-dependent reduction of the nitro groups on nitroaromatic and nitroheterocyclic compounds. Nitroreductases have raised a great interest due to their potential applications in bioremediation, biocatalysis, and biomedicine, especially in prodrug activation for chemotherapeutic cancer treatments. Different bacterial nitroreductases have been purified and their biochemical and kinetic parameters have been determined. The crystal structure of some nitroreductases have also been solved. However, the physiological role(s) of these enzymes remains unclear. Nitroreductase genes are widely spread within bacterial genomes, but are also found in archaea and some eukaryotic species. Although studies on regulation of nitroreductase gene expression are scarce, it seems that nitroreductase genes may be controlled by the MarRA and SoxRS regulatory systems that are involved in responses to several antibiotics and environmental chemical hazards and to specific oxidative stress conditions. This review covers the microbial distribution, types, biochemical properties, structure and regulation of the bacterial nitroreductases. The possible physiological functions and the biotechnological applications of these enzymes are also discussed.

Journal ArticleDOI
TL;DR: The cell envelope stress response will be placed in the context of the overall cellular physiology, demonstrating that its regulatory systems are linked not only to other stress responses but also to the overall homeostasis and lifestyle of Gram-positive bacteria.
Abstract: The bacterial cell envelope is the first and major line of defence against threats from the environment. It is an essential and yet vulnerable structure that gives the cell its shape and counteracts the high internal osmotic pressure. It also provides an important sensory interface and molecular sieve, mediating both information flow and the controlled transport of solutes. The cell envelope is also the target for numerous antibiotics. Therefore, the monitoring and maintenance of cell envelope integrity in the presence of envelope perturbating agents and conditions is crucial for survival. The underlying signal transduction is mediated by two regulatory principles, two-component systems and extracytoplasmic function σ factors, in both the Firmicutes (low-GC) and Actinobacteria (high-GC) branches of Gram-positive bacteria. This study presents a comprehensive overview of cell envelope stress-sensing regulatory systems. This knowledge will then be applied for in-depth comparative genomics analyses to emphasize the distribution and conservation of cell envelope stress-sensing systems. Finally, the cell envelope stress response will be placed in the context of the overall cellular physiology, demonstrating that its regulatory systems are linked not only to other stress responses but also to the overall homeostasis and lifestyle of Gram-positive bacteria.

Journal ArticleDOI
TL;DR: In this article, the authors describe a protein complex, the elongase that inserts disaccharidepentapeptide units at a limited number of discrete sites while using the cytoskeletal MreB helix as a tracking device.
Abstract: For growth and division of rod-shaped bacteria, the cylindrical part of the sacculus has to be elongated and two new cell poles have to be synthesized. The elongation is performed by a protein complex, the elongase that inserts disaccharidepentapeptide units at a limited number of discrete sites while using the cytoskeletal MreB helix as a tracking device. Upon initiation of cell division by positioning of the cytoskeletal Z-ring at mid cell, a switch from dispersed to concentrated local peptidoglycan-synthesis occurs. From this point on, peptidoglycan synthesis is for a large part redirected from elongating activity to synthesis of new cell poles by the divisome. The divisome might be envisioned as an extended elongase because apart from its basic peptidoglycan synthesizing activity, specific functions have to be added. These are conversion from a cylinder to a sphere, invagination of the outer membrane and addition of hydrolases that allow separation of the daughter cells. The elongase and the divisome are dynamic hyperstructures that probably share part of their proteins. Although this multifunctionality and flexibility form a barrier to the functional elucidation of its individual subunits, it helps the cells to survive a variety of emergency situations and to proliferate securely.

Journal ArticleDOI
TL;DR: Having the complete set of structures and genes opens the way for experimental studies on the role of this diversity in pathogenicity, and this is the first such group for which structures and DNA sequences have been determined for all O antigens.
Abstract: This review covers the O antigens of the 46 serotypes of Shigella, but those of most Shigella flexneri are variants of one basic structure, leaving 34 Shigella distinct O antigens to review, together with their gene clusters. Several of the structures and gene clusters are reported for the first time and this is the first such group for which structures and DNA sequences have been determined for all O antigens. Shigella strains are in effect Escherichia coli with a specific mode of pathogenicity, and 18 of the 34 O antigens are also found in traditional E. coli. Three are very similar to E. coli O antigens and 13 are unique to Shigella strains. The O antigen of Shigella sonnei is quite atypical for E. coli and is thought to have transferred from Plesiomonas. The other 12 O antigens unique to Shigella strains have structures that are typical of E. coli, but there are considerably more anomalies in their gene clusters, probably reflecting recent modification of the structures. Having the complete set of structures and genes opens the way for experimental studies on the role of this diversity in pathogenicity.

Journal ArticleDOI
TL;DR: Basic knowledge of sigma and ECF proteins was reviewed with particular emphasis on their role in P. aeruginosa global gene regulation to provide new means to prevent infection, new targets for antimicrobial therapy, as well as new insights into the infection process.
Abstract: In Pseudomonas aeruginosa, as in most bacterial species, the expression of genes is tightly controlled by a repertoire of transcriptional regulators, particularly the so-called sigma (sigma) factors. The basic understanding of these proteins in bacteria has initially been described in Escherichia coli where seven sigma factors are involved in core RNA polymerase interactions and promoter recognition. Now, 7 years have passed since the completion of the first genome sequence of the opportunistic pathogen P. aeruginosa. Information from the genome of P. aeruginosa PAO1 identified 550 transcriptional regulators and 24 putative sigma factors. Of the 24 sigma, 19 were of extracytoplasmic function (ECF). Here, basic knowledge of sigma and ECF proteins was reviewed with particular emphasis on their role in P. aeruginosa global gene regulation. Summarized data are obtained from in silico analysis of P. aeruginosasigma and ECF including rpoD (sigma(70)), RpoH (sigma(32)), RpoF (FliA or sigma(28)), RpoS (sigma(S) or sigma(38)), RpoN (NtrA, sigma(54) or sigma(N)), ECF including AlgU (RpoE or sigma(22)), PvdS, SigX and a collection of uncharacterized sigma ECF, some of which are implicated in iron transport. Coupled to systems biology, identification and functional genomics analysis of P. aeruginosasigma and ECF are expected to provide new means to prevent infection, new targets for antimicrobial therapy, as well as new insights into the infection process.

Journal ArticleDOI
TL;DR: The best strategies are considered for identifying inhibitors of pantothenic acid utilization and biosynthesis that are potent and selective inhibitors of microbial growth and that may be suitable for use as chemotherapeutic agents in humans.
Abstract: Pantothenic acid, a precursor of coenzyme A (CoA), is essential for the growth of pathogenic microorganisms. Since the structure of pantothenic acid was determined, many analogues of this essential metabolite have been prepared. Several have been demonstrated to exert an antimicrobial effect against a range of microorganisms by inhibiting the utilization of pantothenic acid, validating pantothenic acid utilization as a potential novel antimicrobial drug target. This review commences with an overview of the mechanisms by which various microorganisms acquire the pantothenic acid they require for growth, and the universal CoA biosynthesis pathway by which pantothenic acid is converted into CoA. A detailed survey of studies that have investigated the inhibitory activity of analogues of pantothenic acid and other precursors of CoA follows. The potential of inhibitors of both pantothenic acid utilization and biosynthesis as novel antibacterial, antifungal and antimalarial agents is discussed, focusing on inhibitors and substrates of pantothenate kinase, the enzyme catalysing the rate-limiting step of CoA biosynthesis in many organisms. The best strategies are considered for identifying inhibitors of pantothenic acid utilization and biosynthesis that are potent and selective inhibitors of microbial growth and that may be suitable for use as chemotherapeutic agents in humans.

Journal ArticleDOI
TL;DR: The metabolic reconstruction of aromatics degradation is performed, linking the catabolic abilities predicted in silico from the complete genome sequence with the range of compounds that support growth of this bacterium.
Abstract: Cupriavidus necator JMP134 is a model for chloroaromatics biodegradation, capable of mineralizing 2,4-D, halobenzoates, chlorophenols and nitrophenols, among other aromatic compounds. We performed the metabolic reconstruction of aromatics degradation, linking the catabolic abilities predicted in silico from the complete genome sequence with the range of compounds that support growth of this bacterium. Of the 140 aromatic compounds tested, 60 serve as a sole carbon and energy source for this strain, strongly correlating with those catabolic abilities predicted from genomic data. Almost all the main ring-cleavage pathways for aromatic compounds are found in C. necator: the beta-ketoadipate pathway, with its catechol, chlorocatechol, methylcatechol and protocatechuate ortho ring-cleavage branches; the (methyl)catechol meta ring-cleavage pathway; the gentisate pathway; the homogentisate pathway; the 2,3-dihydroxyphenylpropionate pathway; the (chloro)hydroxyquinol pathway; the (amino)hydroquinone pathway; the phenylacetyl-CoA pathway; the 2-aminobenzoyl-CoA pathway; the benzoyl-CoA pathway and the 3-hydroxyanthranilate pathway. A broad spectrum of peripheral reactions channel substituted aromatics into these ring cleavage pathways. Gene redundancy seems to play a significant role in the catabolic potential of this bacterium. The literature on the biochemistry and genetics of aromatic compounds degradation is reviewed based on the genomic data. The findings on aromatic compounds biodegradation in C. necator reviewed here can easily be extrapolated to other environmentally relevant bacteria, whose genomes also possess a significant proportion of catabolic genes.

Journal ArticleDOI
TL;DR: Genomic and genetic analyses show that the diffusible signal factor QS-signaling pathway regulates diverse biological functions including virulence, biofilm dispersal, and ecological competence.
Abstract: It is now clear that cell-cell communication, often referred to as quorum sensing (QS), is the norm in the prokaryotic kingdom and this community-wide genetic regulatory mechanism has been adopted for regulation of many important biological functions. Since the 1980s, several types of QS signals have been identified, which are associated commonly with different types of QS mechanisms. Among them, the diffusible signal factor (DSF)-dependent QS system, originally discovered from bacterial pathogen Xanthomonas campestris pv. campestris, is a relatively new regulatory mechanism. The rapid research progress over the last few years has identified the chemical structure of the QS signal DSF, established the DSF regulon, and unveiled the general signaling pathways and mechanisms. Particular noteworthy are that DSF biosynthesis is modulated by a novel posttranslational autoinduction mechanism involving protein-protein interaction between the DSF synthase RpfF and the sensor RpfC, and that QS signal sensing is coupled to intracellular regulatory networks through a second messenger cyclic-di-GMP and a global regulator Clp. Genomic and genetic analyses show that the DSF QS-signaling pathway regulates diverse biological functions including virulence, biofilm dispersal, and ecological competence. Moreover, evidence is emerging that the DSF QS system is conserved in a range of plant and human bacterial pathogens.

Journal ArticleDOI
TL;DR: It is shown that in Saccharomyces cerevisiae, sensing systems for other nutrients share some of the characteristics of the glucose-sensing pathways, as well as other regulatory elements whose functions are still incompletely understood.
Abstract: In the presence of glucose, yeast undergoes an important remodelling of its metabolism. There are changes in the concentration of intracellular metabolites and in the stability of proteins and mRNAs; modifications occur in the activity of enzymes as well as in the rate of transcription of a large number of genes, some of the genes being induced while others are repressed. Diverse combinations of input signals are required for glucose regulation of gene expression and of other cellular processes. This review focuses on the early elements in glucose signalling and discusses their relevance for the regulation of specific processes. Glucose sensing involves the plasma membrane proteins Snf3, Rgt2 and Gpr1 and the glucose-phosphorylating enzyme Hxk2, as well as other regulatory elements whose functions are still incompletely understood. The similarities and differences in the way in which yeasts and mammalian cells respond to glucose are also examined. It is shown that in Saccharomyces cerevisiae, sensing systems for other nutrients share some of the characteristics of the glucose-sensing pathways.

Journal ArticleDOI
TL;DR: A total of 28 conserved genes present in various magnetic bacteria were identified to be specifically associated with the magnetotactic phenotype, most of which are located in the genomic magnetosome island.
Abstract: The ability of magnetotactic bacteria (MTB) to orient in magnetic fields is based on the synthesis of magnetosomes, which are unique prokaryotic organelles comprising membrane-enveloped, nano-sized crystals of a magnetic iron mineral that are aligned in well-ordered intracellular chains. Magnetosome crystals have species-specific morphologies, sizes, and arrangements. The magnetosome membrane, which originates from the cytoplasmic membrane by invagination, represents a distinct subcellular compartment and has a unique biochemical composition. The roughly 20 magnetosome-specific proteins have functions in vesicle formation, magnetosomal iron transport, and the control of crystallization and intracellular arrangement of magnetite particles. The assembly of magnetosome chains is under genetic control and involves the action of an acidic protein that links magnetosomes to a novel cytoskeletal structure, presumably formed by a specific actin-like protein. A total of 28 conserved genes present in various magnetic bacteria were identified to be specifically associated with the magnetotactic phenotype, most of which are located in the genomic magnetosome island. The unique properties of magnetosomes attracted broad interdisciplinary interest, and MTB have recently emerged as a model to study prokaryotic organelle formation and evolution.

Journal ArticleDOI
TL;DR: The present review aims to integrate older ultra-structural data with recent localization studies, in order to clarify the relation between the mechanisms of cell wall synthesis and the determination of cell shape in various cocci.
Abstract: The shape of bacteria is determined by their cell wall and can be very diverse. Even among genera with the suffix ‘cocci’, which are the focus of this review, different shapes exist. While staphylococci or Neisseria cells, for example, are truly round-shaped, streptococci, lactococci or enterococci have an ovoid shape. Interestingly, there seems to be a correlation between the shape of an organism and its set of penicillin-binding proteins – the enzymes that assemble the peptidoglycan, the main constituent of the cell wall. While only one peptidoglycan biosynthesis machinery seems to exist in staphylococci, two of these machineries are proposed to function in ovoid-shaped bacteria, reinforcing the intrinsic differences regarding the morphogenesis of different classes of cocci. The present review aims to integrate older ultra-structural data with recent localization studies, in order to clarify the relation between the mechanisms of cell wall synthesis and the determination of cell shape in various cocci.

Journal ArticleDOI
TL;DR: Phage dynamics and global transcriptome shifts are considered to be responsible for the pathogenicity of S. aureus, indicating the existence of other mechanisms for the genesis of C-MRSA.
Abstract: Staphylococcus aureus is an opportunistic pathogen and the major causative agent of numerous hospital- and community-acquired infections. Multilocus sequence typing reveals a highly clonal structure for S. aureus. Although infrequently occurring across clonal complexes, homologous recombination still contributed to the evolution of this species over the long term. agr-mediated bacterial interference has divided S. aureus into four groups, which are independent of clonality and provide another view on S. aureus evolution. Genome sequencing of nine S. aureus strains has helped identify a number of virulence factors, but the key determinants for infection are still unknown. Comparison of commensal and pathogenic strains shows no difference in diversity or clonal assignments. Thus, phage dynamics and global transcriptome shifts are considered to be responsible for the pathogenicity. Community-acquired methicillin-resistant S. aureus (C-MRSA) is characterized by a short SCCmec and the presence of a Panton-Valentine leukocidin locus, but no studies have proven their exact biologic roles in C-MRSA infection, indicating the existence of other mechanisms for the genesis of C-MRSA.

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TL;DR: This review highlights the main genetic features of circular bacteriocins, which require the co-ordinated expression of several genetic determinants, and summarizes the progress made in the understanding of their principal genetic features over the last few years.
Abstract: This review highlights the main genetic features of circular bacteriocins, which require the co-ordinated expression of several genetic determinants. In general terms, it has been demonstrated that the expression of such structural genes must be combined with the activity of proteins involved in maturation (cleavage/circularization) and secretion outside the cell via different transporter systems, as well as multifaceted immunity mechanisms essential to ensuring the bacteria's self-protection against such strong inhibitors. Several circular antibacterial peptides produced by Gram-positive bacteria have been described to date, including enterocin AS-48, from Enterococcus faecalis S-48 (the first one characterized), gassericin A, from Lactobacillus gasseri LA39, and a similar one, reutericin 6, from Lactobacillus reuteri LA6, butyrivibriocin AR10, from the ruminal anaerobe Butyrivibrio fibrisolvens AR10, uberolysin, from Streptococcus uberis, circularin A, from Clostridium beijerinckii ATCC 25752, and subtilosin A, from Bacillus subtilis. We summarize here the progress made in the understanding of their principal genetic features over the last few years, during which the functional roles of circular proteins with wide biological activity have become clearer.

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TL;DR: Although there is good evidence to support the notion that the induced immune response and protection afforded against tuberculosis differs between BCG vaccine strains, currently, there are insufficient data to favour or recommend one particular strain.
Abstract: The Bacille Calmette-Guerin (BCG) vaccine has been used for more than 80 years to protect against tuberculosis. Worldwide, over 90% of children are immunized with BCG, making it the most commonly administered vaccine, with more than 120 million doses used each year. Although new tuberculosis vaccines are under investigation, BCG will remain the cornerstone of the strategy to fight the worsening tuberculosis pandemic for the foreseeable future. The recent delineation of genetic differences between BCG vaccine strains has renewed interest in the influence of the vaccine strain on the protective efficacy against tuberculosis. This review critically examines the data from animal and human studies comparing BCG vaccine strains. Although there is good evidence to support the notion that the induced immune response and protection afforded against tuberculosis differs between BCG vaccine strains, currently, there are insufficient data to favour or recommend one particular strain. Identifying BCG strains with superior protection would have a dramatic effect on tuberculosis control at a population level: a small increment in protection provided by BCG immunization will prevent large numbers of cases of severe tuberculosis and deaths, particularly in children.