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      The Success of Acinetobacter Species; Genetic, Metabolic and Virulence Attributes

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          Abstract

          An understanding of why certain Acinetobacter species are more successful in causing nosocomial infections, transmission and epidemic spread in healthcare institutions compared with other species is lacking. We used genomic, phenotypic and virulence studies to identify differences between Acinetobacter species. Fourteen strains representing nine species were examined. Genomic analysis of six strains showed that the A. baumannii core genome contains many genes important for diverse metabolism and survival in the host. Most of the A. baumannii core genes were also present in one or more of the less clinically successful species. In contrast, when the accessory genome of an individual A. baumannii strain was compared to a strain of a less successful species ( A. calcoaceticus RUH2202), many operons with putative virulence function were found to be present only in the A. baumannii strain, including the csu operon, the acinetobactin chromosomal cluster, and bacterial defence mechanisms. Phenotype microarray analysis showed that compared to A. calcoaceticus (RUH2202), A. baumannii ATCC 19606 T was able to utilise nitrogen sources more effectively and was more tolerant to pH, osmotic and antimicrobial stress. Virulence differences were also observed, with A. baumannii ATCC 19606 T, A. pittii SH024, and A. nosocomialis RUH2624 persisting and forming larger biofilms on human skin than A. calcoaceticus. A. baumannii ATCC 19606 T and A. pittii SH024 were also able to survive in a murine thigh infection model, whereas the other two species were eradicated. The current study provides important insights into the elucidation of differences in clinical relevance among Acinetobacter species.

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          Most cited references40

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          Multiple sequence alignment with the Clustal series of programs.

          R Chenna (2003)
          The Clustal series of programs are widely used in molecular biology for the multiple alignment of both nucleic acid and protein sequences and for preparing phylogenetic trees. The popularity of the programs depends on a number of factors, including not only the accuracy of the results, but also the robustness, portability and user-friendliness of the programs. New features include NEXUS and FASTA format output, printing range numbers and faster tree calculation. Although, Clustal was originally developed to run on a local computer, numerous Web servers have been set up, notably at the EBI (European Bioinformatics Institute) (http://www.ebi.ac.uk/clustalw/).
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            Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development.

            The formation of complex bacterial communities known as biofilms begins with the interaction of planktonic cells with a surface in response to appropriate environmental signals. We report the isolation and characterization of mutants of Pseudomonas aeruginosa PA14 defective in the initiation of biofilm formation on an abiotic surface, polyvinylchloride (PVC) plastic. These mutants are designated surface attachment defective (sad ). Two classes of sad mutants were analysed: (i) mutants defective in flagellar-mediated motility and (ii) mutants defective in biogenesis of the polar-localized type IV pili. We followed the development of the biofilm formed by the wild type over 8 h using phase-contrast microscopy. The wild-type strain first formed a monolayer of cells on the abiotic surface, followed by the appearance of microcolonies that were dispersed throughout the monolayer of cells. Using time-lapse microscopy, we present evidence that microcolonies form by aggregation of cells present in the monolayer. As observed with the wild type, strains with mutations in genes required for the synthesis of type IV pili formed a monolayer of cells on the PVC plastic. However, in contrast to the wild-type strain, the type IV pili mutants did not develop microcolonies over the course of the experiments, suggesting that these structures play an important role in microcolony formation. Very few cells of a non-motile strain (carrying a mutation in flgK) attached to PVC even after 8 h of incubation, suggesting a role for flagella and/or motility in the initial cell-to-surface interactions. The phenotype of these mutants thus allows us to initiate the dissection of the developmental pathway leading to biofilm formation.
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              The phosphate regulon and bacterial virulence: a regulatory network connecting phosphate homeostasis and pathogenesis.

              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 (P(i)) levels. Under conditions of P(i) 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.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                29 October 2012
                : 7
                : 10
                : e46984
                Affiliations
                [1 ]Department of Microbiology, Monash University, Melbourne, Victoria, Australia
                [2 ]Department of Infectious Diseases, Alfred Hospital, Melbourne, Victoria, Australia
                [3 ]Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America
                [4 ]Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
                [5 ]Department of Genetics and Center for Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, Ohio, United States of America
                [6 ]Agrobiology and Pedology Centre, Agricultural Research Council (CRA-ABP), Florence, Italy
                [7 ]Department of Evolutionary Biology, University of Florence, Florence, Italy
                [8 ]Broad Institute, Cambridge, Massachusetts, United States of America
                [9 ]University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital Campus, Brisbane, Queensland, Australia
                [10 ]Institute for Medical Microbiology, Immunology, and Hygiene, University of Cologne, Cologne, Germany
                University of Florida, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: AYP AdB PHN HS LD. Performed the experiments: AYP AdB MDA GMC SM MG AME DVW. Analyzed the data: AYP AdB MDA GMC SM MG PHN AME DVW DLP HS LD. Contributed reagents/materials/analysis tools: AYP MDA GMC SM MG PHN AME DVW DLP HS LD. Wrote the paper: AYP.

                Article
                PONE-D-12-13379
                10.1371/journal.pone.0046984
                3483291
                23144699
                19137dd1-122f-4497-b970-febda86f410e
                Copyright @ 2012

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 11 May 2012
                : 7 September 2012
                Page count
                Pages: 11
                Funding
                This work was supported in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under the HMP Jumpstart Initiative. The authors also acknowledge support from the Australian National Health and Medical Research Council (NHMRC) project grant (APP1010114) and an NHMRC Biomedical Fellowship to A.Y.P (APP606961). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Computational Biology
                Genomics
                Comparative Genomics
                Genome Expression Analysis
                Microarrays
                Model Organisms
                Animal Models
                Mouse
                Medicine
                Infectious Diseases
                Bacterial Diseases
                Acinetobacter Infections
                Acinetobacter Baumannii

                Uncategorized
                Uncategorized

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