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      Co-infecting microbes dramatically alter pathogen gene essentiality during polymicrobial infection

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          Abstract

          Identifying genes required by pathogens during infection is critical for antimicrobial development. Here, we used a Monte Carlo simulation-based method to analyze high-throughput transposon sequencing data to determine the role of infection site and co-infecting microbes on the in vivo ‘essential’ genome of Staphylococcus aureus. We discovered that co-infection of murine surgical wounds with Pseudomonas aeruginosa results in conversion of ~25% of the in vivo S. aureus mono-culture essential genes to non-essential. Furthermore, 182 S. aureus genes are uniquely essential during co-infection. These “ Community Dependent Essential” (CoDE) genes illustrate the importance of studying pathogen gene essentiality in polymicrobial communities.

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          Most cited references31

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          Waves of resistance: Staphylococcus aureus in the antibiotic era.

          Staphylococcus aureus is notorious for its ability to become resistant to antibiotics. Infections that are caused by antibiotic-resistant strains often occur in epidemic waves that are initiated by one or a few successful clones. Methicillin-resistant S. aureus (MRSA) features prominently in these epidemics. Historically associated with hospitals and other health care settings, MRSA has now emerged as a widespread cause of community infections. Community or community-associated MRSA (CA-MRSA) can spread rapidly among healthy individuals. Outbreaks of CA-MRSA infections have been reported worldwide, and CA-MRSA strains are now epidemic in the United States. Here, we review the molecular epidemiology of the epidemic waves of penicillin- and methicillin-resistant strains of S. aureus that have occurred since 1940, with a focus on the clinical and molecular epidemiology of CA-MRSA.
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            Transposon insertion sequencing: a new tool for systems-level analysis of microorganisms.

            Our knowledge of gene function has increasingly lagged behind gene discovery, hindering our understanding of the genetic basis of microbial phenotypes. Recently, however, massively parallel sequencing has been combined with traditional transposon mutagenesis in techniques referred to as transposon sequencing (Tn-seq), high-throughput insertion tracking by deep sequencing (HITS), insertion sequencing (INSeq) and transposon-directed insertion site sequencing (TraDIS), making it possible to identify putative gene functions in a high-throughput manner. Here, we describe the similarities and differences of these related techniques and discuss their application to the probing of gene function and higher-order genome organization.
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              Multiple bacterial species reside in chronic wounds: a longitudinal study.

              The aim of the study was to investigate the bacterial profile of chronic venous leg ulcers and the importance of the profile to ulcer development. Patients with persisting venous leg ulcers were included and followed for 8 weeks. Every second week, ulcer samples were collected and the bacterial species present were identified. More than one bacterial species were detected in all the ulcers. The most common bacteria found were Staphylococcus aureus (found in 93.5% of the ulcers), Enterococcus faecalis (71.7%), Pseudomonas aeruginosa (52.2%), coagulase-negative staphylococci (45.7%), Proteus species (41.3%) and anaerobic bacteria (39.1%). Resident bacterial species were present in all the ulcers. In 76% of the ulcers, two or more (up to five) resident bacterial species were found. The most common resident bacterial species were S. aureus and P. aeruginosa. Furthermore, ulcers with P. aeruginosa were found to be significantly larger than ulcers without the presence of P. aeruginosa (P < 0.005). Our study demonstrated that the chronic wound is colonised by multiple bacterial species and that once they are established many of them persist in the wound. Our results suggest that the presence of P. aeruginosa in venous leg ulcers can induce ulcer enlargement and/or cause delayed healing.
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                Author and article information

                Journal
                101674869
                44774
                Nat Microbiol
                Nat Microbiol
                Nature microbiology
                2058-5276
                12 January 2018
                30 May 2017
                30 May 2017
                19 January 2018
                : 2
                : 17079
                Affiliations
                [a ]Department of Molecular Biosciences, Institute of Cellular and Molecular Biology, LaMontagne Center for Infectious Disease, The University of Texas at Austin, Austin, TX, USA
                [b ]Department of Surgery, Texas Tech University Health Sciences Center, Lubbock, TX, USA
                [c ]Department of Ophthalmology and Department of Microbiology and Immunobiology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA
                Author notes
                [1 ]Corresponding Author: Marvin Whiteley, Department of Molecular Biosciences, The University of Texas at Austin, 1 University Station, A5000, Austin, TX 78712, Ph: 512-471-5493, mwhiteley@ 123456austin.utexas.edu
                Article
                NIHMS868650
                10.1038/nmicrobiol.2017.79
                5774221
                28555625
                c6dcb746-3fd8-4a2d-93ea-ab97d2d49c3d

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                Article

                staphylococcus,pseudomonas,wound infection,essential genome,code genes,aggregatibacter

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