scholarly journals Two Novel Membrane Proteins, TcpD and TcpE, Are Essential for Conjugative Transfer of pCW3 in Clostridium perfringens

2014 ◽  
Vol 197 (4) ◽  
pp. 774-781 ◽  
Author(s):  
Jessica A. Wisniewski ◽  
Wee L. Teng ◽  
Trudi L. Bannam ◽  
Julian I. Rood
Keyword(s):  
Clostridium Perfringens ◽  
Cell Envelope ◽  
Tetracycline Resistance ◽  
Conjugative Plasmid ◽  
Conjugative Transfer ◽  
Western Blots ◽  
Content Type ◽  
Essential Components ◽  
Encoded Proteins ◽  
Transfer Apparatus

The anaerobic pathogenClostridium perfringensencodes either toxin genes or antibiotic resistance determinants on a unique family of conjugative plasmids that have a novel conjugation region, thetcplocus. Studies of the paradigm conjugative plasmid fromC. perfringens, the 47-kb tetracycline resistance plasmid pCW3, have identified severaltcp-encoded proteins that are involved in conjugative transfer and form part of the transfer apparatus. In this study, the role of the conserved hypothetical proteins TcpD, TcpE, and TcpJ was examined. Mutation and complementation analyses showed that TcpD and TcpE were essential for the conjugative transfer of pCW3, whereas TcpJ was not required. To analyze the TcpD and TcpE proteins inC. perfringens, functional hemagglutinin (HA)-tagged derivatives were constructed. Western blots showed that TcpD and TcpE localized to the cell envelope fraction independently of the presence of other pCW3-encoded proteins. Finally, examination of the subcellular localization of TcpD and TcpE by immunofluorescence showed that these proteins were concentrated at both poles ofC. perfringensdonor cells, where they are postulated to form essential components of the multiprotein complex that comprises the transfer apparatus.

scholarly journals Conjugation-Mediated Horizontal Gene Transfer of Clostridium perfringens Plasmids in the Chicken Gastrointestinal Tract Results in the Formation of New Virulent Strains

2017 ◽  
Vol 83 (24) ◽  
Author(s):  
Jake A. Lacey ◽  
Anthony L. Keyburn ◽  
Mark E. Ford ◽  
Ricardo W. Portela ◽  
Priscilla A. Johanesen ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Clostridium Perfringens ◽  
Plasmid Transfer ◽  
Conjugative Plasmid ◽  
Conjugative Transfer ◽  
Necrotic Enteritis ◽  
Content Type ◽  
Gastrointestinal Pathogen

ABSTRACT Clostridium perfringens is a gastrointestinal pathogen capable of causing disease in a variety of hosts. Necrotic enteritis in chickens is caused by C. perfringens strains that produce the pore-forming toxin NetB, the major virulence factor for this disease. Like many other C. perfringens toxins and antibiotic resistance genes, NetB is encoded on a conjugative plasmid. Conjugative transfer of the netB-containing plasmid pJIR3535 has been demonstrated in vitro with a netB-null mutant. This study has investigated the effect of plasmid transfer on disease pathogenesis, with two genetically distinct transconjugants constructed under in vitro conditions, within the intestinal tract of chickens. This study also demonstrates that plasmid transfer can occur naturally in the host gut environment without the need for antibiotic selective pressure to be applied. The demonstration of plasmid transfer within the chicken host may have implications for the progression and pathogenesis of C. perfringens-mediated disease. Such horizontal gene transfer events are likely to be common in the clostridia and may be a key factor in strain evolution, both within animals and in the wider environment. IMPORTANCE Clostridium perfringens is a major gastrointestinal pathogen of poultry. C. perfringens strains that express the NetB pore-forming toxin, which is encoded on a conjugative plasmid, cause necrotic enteritis. This study demonstrated that the conjugative transfer of the netB-containing plasmid to two different nonpathogenic strains converted them into disease-causing strains with disease-causing capability similar to that of the donor strain. Plasmid transfer of netB and antibiotic resistance was also demonstrated to occur within the gastrointestinal tract of chickens, with approximately 14% of the isolates recovered comprising three distinct, in vivo-derived, transconjugant types. The demonstration of in vivo plasmid transfer indicates the potential importance of strain plasticity and the contribution of plasmids to strain virulence.

scholarly journals The Putative Coupling Protein TcpA Interacts with Other pCW3-Encoded Proteins To Form an Essential Part of the Conjugation Complex

2009 ◽  
Vol 191 (9) ◽  
pp. 2926-2933 ◽  
Author(s):  
Jennifer A. Steen ◽  
Trudi L. Bannam ◽  
Wee Lin Teng ◽  
Rodney J. Devenish ◽  
Julian I. Rood
Keyword(s):  
Protein Interactions ◽  
Tetracycline Resistance ◽  
Conjugative Plasmid ◽  
Conjugative Transfer ◽  
Protein Protein Interactions ◽  
Coupling Protein ◽  
Derivatives Of ◽  
Two Hybrid ◽  
Chemical Cross Linking ◽  
Transfer Apparatus

ABSTRACT Conjugative plasmids encode antibiotic resistance determinants or toxin genes in the anaerobic pathogen Clostridium perfringens. The paradigm conjugative plasmid in this bacterium is pCW3, a 47-kb tetracycline resistance plasmid that encodes the unique tcp transfer locus. The tcp locus consists of 11 genes, intP and tcpA-tcpJ, at least three of which, tcpA, tcpF, and tcpH, are essential for the conjugative transfer of pCW3. In this study we examined protein-protein interactions involving TcpA, the putative coupling protein. Use of a bacterial two-hybrid system identified interactions between TcpA and TcpC, TcpG, and TcpH. This analysis also demonstrated TcpA, TcpC, and TcpG self-interactions, which were confirmed by chemical cross-linking studies. Examination of a series of deletion and site-directed derivatives of TcpA identified the domains and motifs required for these interactions. Based on these results, we have constructed a model for this unique conjugative transfer apparatus.

scholarly journals TcpA, an FtsK/SpoIIIE Homolog, Is Essential for Transfer of the Conjugative Plasmid pCW3 in Clostridium perfringens

2007 ◽  
Vol 189 (21) ◽  
pp. 7782-7790 ◽  
Author(s):  
Jennifer A. Parsons ◽  
Trudi L. Bannam ◽  
Rodney J. Devenish ◽  
Julian I. Rood
Keyword(s):  
Clostridium Perfringens ◽  
Essential Role ◽  
Tetracycline Resistance ◽  
Conjugative Plasmid ◽  
Conjugative Transfer ◽  
Binding Motifs ◽  
Coupling Protein ◽  
Conjugation Process ◽  
Dna Translocase

ABSTRACT The conjugative tetracycline resistance plasmid pCW3 is the paradigm conjugative plasmid in the anaerobic gram-positive pathogen Clostridium perfringens. Two closely related FtsK/SpoIIIE homologs, TcpA and TcpB, are encoded on pCW3, which is significant since FtsK domains are found in coupling proteins of gram-negative conjugation systems. To develop an understanding of the mechanism of conjugative transfer in C. perfringens, we determined the role of these proteins in the conjugation process. Mutation and complementation analysis was used to show that the tcpA gene was essential for the conjugative transfer of pCW3 and that the tcpB gene was not required for transfer. Furthermore, complementation of a pCW3ΔtcpA mutant with divergent tcpA homologs provided experimental evidence that all of the known conjugative plasmids from C. perfringens use a similar transfer mechanism. Functional genetic analysis of the TcpA protein established the essential role in conjugative transfer of its Walker A and Walker B ATP-binding motifs and its FtsK-like RAAG motif. It is postulated that TcpA is the essential DNA translocase or coupling protein encoded by pCW3 and as such represents a key component of the unique conjugation process in C. perfringens.

scholarly journals Transposase-Mediated Excision, Conjugative Transfer, and Diversity of ICE6013 Elements in Staphylococcus aureus

2017 ◽  
Vol 199 (8) ◽  
Author(s):  
Emily A. Sansevere ◽  
Xiao Luo ◽  
Joo Youn Park ◽  
Sunghyun Yoon ◽  
Keun Seok Seo ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Sequence Analysis ◽  
Integration Site ◽  
Consensus Sequence ◽  
Open Reading Frames ◽  
Conjugative Plasmid ◽  
Site Preference ◽  
Conjugative Transfer ◽  
Content Type ◽  
Integrative Conjugative Elements

ABSTRACT ICE6013 represents one of two families of integrative conjugative elements (ICEs) identified in the pan-genome of the human and animal pathogen Staphylococcus aureus. Here we investigated the excision and conjugation functions of ICE6013 and further characterized the diversity of this element. ICE6013 excision was not significantly affected by growth, temperature, pH, or UV exposure and did not depend on recA. The IS30-like DDE transposase (Tpase; encoded by orf1 and orf2) of ICE6013 must be uninterrupted for excision to occur, whereas disrupting three of the other open reading frames (ORFs) on the element significantly affects the level of excision. We demonstrate that ICE6013 conjugatively transfers to different S. aureus backgrounds at frequencies approaching that of the conjugative plasmid pGO1. We found that excision is required for conjugation, that not all S. aureus backgrounds are successful recipients, and that transconjugants acquire the ability to transfer ICE6013. Sequencing of chromosomal integration sites in serially passaged transconjugants revealed a significant integration site preference for a 15-bp AT-rich palindromic consensus sequence, which surrounds the 3-bp target site that is duplicated upon integration. A sequence analysis of ICE6013 from different host strains of S. aureus and from eight other species of staphylococci identified seven divergent subfamilies of ICE6013 that include sequences previously classified as a transposon, a plasmid, and various ICEs. In summary, these results indicate that the IS30-like Tpase functions as the ICE6013 recombinase and that ICE6013 represents a diverse family of mobile genetic elements that mediate conjugation in staphylococci. IMPORTANCE Integrative conjugative elements (ICEs) encode the abilities to integrate into and excise from bacterial chromosomes and plasmids and mediate conjugation between bacteria. As agents of horizontal gene transfer, ICEs may affect bacterial evolution. ICE6013 represents one of two known families of ICEs in the pathogen Staphylococcus aureus, but its core functions of excision and conjugation are not well studied. Here, we show that ICE6013 depends on its IS30-like DDE transposase for excision, which is unique among ICEs, and we demonstrate the conjugative transfer and integration site preference of ICE6013. A sequence analysis revealed that ICE6013 has diverged into seven subfamilies that are dispersed among staphylococci.

scholarly journals Necrotic Enteritis-Derived Clostridium perfringens Strain with Three Closely Related Independently Conjugative Toxin and Antibiotic Resistance Plasmids

mBio ◽  
2011 ◽  
Vol 2 (5) ◽  
Author(s):  
Trudi L. Bannam ◽  
Xu-Xia Yan ◽  
Paul F. Harrison ◽  
Torsten Seemann ◽  
Anthony L. Keyburn ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Clostridium Perfringens ◽  
Tetracycline Resistance ◽  
Necrotic Enteritis ◽  
Sequencing Analysis ◽  
Content Type ◽  
Conjugative Plasmids ◽  
Resistance Plasmid ◽  
Large Plasmids ◽  
Beta2 Toxin

ABSTRACTThe pathogenesis of avian necrotic enteritis involves NetB, a pore-forming toxin produced by virulent avian isolates ofClostridium perfringenstype A. To determine the location and mobility of thenetBstructural gene, we examined a derivative of the tetracycline-resistant necrotic enteritis strain EHE-NE18, in whichnetBwas insertionally inactivated by the chloramphenicol and thiamphenicol resistance genecatP. Both tetracycline and thiamphenicol resistance could be transferred either together or separately to a recipient strain in plate matings. The separate transconjugants could act as donors in subsequent matings, which demonstrated that the tetracycline resistance determinant and thenetBgene were present on different conjugative elements. Large plasmids were isolated from the transconjugants and analyzed by high-throughput sequencing. Analysis of the resultant data indicated that there were actually three large conjugative plasmids present in the original strain, each with its own toxin or antibiotic resistance locus. Each plasmid contained a highly conserved 40-kb region that included plasmid replication and transfer regions that were closely related to the 47-kb conjugative tetracycline resistance plasmid pCW3 fromC. perfringens. The plasmids were as follows: (i) a conjugative 49-kb tetracycline resistance plasmid that was very similar to pCW3, (ii) a conjugative 82-kb plasmid that contained thenetBgene and other potential virulence genes, and (iii) a 70-kb plasmid that carried thecpb2gene, which encodes a different pore-forming toxin, beta2 toxin.IMPORTANCEThe anaerobic bacteriumClostridium perfringenscan cause an avian gastrointestinal disease known as necrotic enteritis. Disease pathogenesis is not well understood, although the plasmid-encoded pore-forming toxin NetB, is an important virulence factor. In this work, we have shown that the plasmid that carries thenetBgene is conjugative and has a 40-kb region that is very similar to replication and transfer regions found within each of the sequenced conjugative plasmids fromC. perfringens. We also showed that this strain contained two additional large plasmids that were also conjugative and carried a similar 40-kb region. One of these plasmids encoded beta2 toxin, and the other encoded tetracycline resistance. To our knowledge, this is the first report of a bacterial strain that carries three closely related but different independently conjugative plasmids. These results have significant implications for our understanding of the transmission of virulence and antibiotic resistance genes in pathogenic bacteria.

scholarly journals Photobacterium damselaesubsp.damselae, a Generalist Pathogen with Unique Virulence Factors and High Genetic Diversity

2018 ◽  
Vol 200 (15) ◽  
Author(s):  
Carlos R. Osorio ◽  
Ana Vences ◽  
Xosé M. Matanza ◽  
Mateus S. Terceti
Keyword(s):  
Genetic Diversity ◽  
Virulence Factors ◽  
Cell Envelope ◽  
Fatal Outcome ◽  
Regulatory System ◽  
Cytolytic Activity ◽  
Conjugative Plasmid ◽  
Marine Animals ◽  
High Genetic Diversity ◽  
Content Type

ABSTRACTPhotobacterium damselaesubsp.damselaecauses vibriosis in a variety of marine animals, including fish species of importance in aquaculture. It also may cause wound infections in humans that can progress to a fatal outcome. Two major virulence factors are encoded within the large conjugative plasmid pPHDD1, the phospholipase D damselysin (Dly) and the pore-forming toxin phobalysin P (PhlyP). The two toxins exert hemolytic and cytolytic activities in a synergistic manner. Even though PhlyP has close homologues in manyVibriospecies, it has unique features that differentiate it from related toxins. Dly phospholipase constitutes a singular trait ofP. damselaesubsp.damselaeamong theVibrionaceae, although related toxins are found in members of theAeromonadaceae. Fish farm outbreaks can also be caused by plasmidless strains. Such observations led to the characterization of two ubiquitous chromosome-encoded toxins with lesser cytolytic activity, the pore forming-toxin phobalysin C (PhlyC) and the phospholipase-hemolysin PlpV. The high genetic diversity of this pathogen deserves special attention, as it has a number of strain-specific features, including the cell envelope polysaccharide synthesis clusters. Fish outbreaks are likely caused by multiclonal populations which contain both plasmidless and pPHDD1-harboring isolates and not by well-adapted clonal complexes. Still, among such genetic heterogeneity, it is feasible to identify conserved weak points in the biology of this bacterium: the two-component regulatory system RstAB (CarSR) was found to be necessary for the maximal production of virulence factors, and its inactivation severely impaired virulence.

scholarly journals Functional Analysis of a Bacitracin Resistance Determinant Located on ICECp1, a Novel Tn916-Like Element from a Conjugative Plasmid in Clostridium perfringens

2015 ◽  
Vol 59 (11) ◽  
pp. 6855-6865 ◽  
Author(s):  
Xiaoyan Han ◽  
Xiang-Dang Du ◽  
Luke Southey ◽  
Dieter M. Bulach ◽  
Torsten Seemann ◽  
...  
Keyword(s):  
Clostridium Perfringens ◽  
Wild Type Strain ◽  
Regulatory Gene ◽  
Conjugative Plasmid ◽  
Resistance Determinant ◽  
Toxin Gene ◽  
Resistance Locus ◽  
Necrotic Enteritis ◽  
Content Type ◽  
Integrative Conjugative Elements

ABSTRACTBacitracins are mixtures of structurally related cyclic polypeptides with antibiotic properties. They act by interfering with the biosynthesis of the bacterial cell wall. In this study, we analyzed an avian necrotic enteritis strain ofClostridium perfringensthat was resistant to bacitracin and produced NetB toxin. We identified a bacitracin resistance locus that resembled a bacitracin resistance determinant fromEnterococcus faecalis. It contained the structural genesbcrABDand a putative regulatory gene,bcrR. Mutagenesis studies provided evidence that bothbcrAandbcrBare essential for bacitracin resistance, and that evidence was supported by the results of experiments in which the introduction of both thebcrAandbcrBgenes into a bacitracin-susceptibleC. perfringensstrain was required to confer bacitracin resistance. The wild-type strain was shown to contain at least three large, putatively conjugative plasmids, and thebcrRABDlocus was localized to an 89.7-kb plasmid, pJIR4150. This plasmid was experimentally shown to be conjugative and was sequenced. The sequence revealed that it also carries atpeLtoxin gene and is related to the pCW3 family of conjugative antibiotic resistance and toxin plasmids fromC. perfringens. Thebcrgenes were located on a genetic element, ICECp1, which is related to the Tn916family of integrative conjugative elements (ICEs). ICECp1appears to be the first Tn916-like element shown to confer bacitracin resistance. In summary, we identified in a toxin-producingC. perfringensstrain a novel mobile bacitracin resistance element which was experimentally shown to be essential for bacitracin resistance and is carried by a putative ICE located on a conjugative plasmid.

scholarly journals pSK41-Like Plasmid Is Necessary for Inc18-LikevanAPlasmid Transfer from Enterococcus faecalis to Staphylococcus aureusIn Vitro

2012 ◽  
Vol 57 (1) ◽  
pp. 212-219 ◽  
Author(s):  
Wenming Zhu ◽  
Nancye Clark ◽  
Jean B. Patel
Keyword(s):  
Enterococcus Faecalis ◽  
The United States ◽  
Conjugal Transfer ◽  
Conjugative Plasmid ◽  
Conjugative Transfer ◽  
Content Type ◽  
A Cell ◽  
Extracellular Factor ◽  
Vancomycin Resistant

ABSTRACTVancomycin-resistantStaphylococcus aureus(VRSA) is thought to result from thein vivoconjugative transfer of avanAplasmid from anEnterococcussp. toS. aureus. We studied bacterial isolates from VRSA cases that occurred in the United States to identify microbiological factors which may contribute to this plasmid transfer. First, vancomycin-susceptible, methicillin-resistantS. aureus(MRSA) isolates from five VRSA cases were tested for their ability to accept foreign DNA by conjugation in mating experiments withEnterococcus faecalisJH2-2 containing pAM378, a pheromone-response conjugative plasmid. All of the MRSA isolates accepted the plasmid DNA with similar transfer efficiencies (∼10−7/donor CFU) except for one isolate, MRSA8, for which conjugation was not successful. The MRSA isolates were also tested as recipients in mating experiments between anE. faecalisisolate with an Inc18-likevanAplasmid that was isolated from a VRSA case patient. Conjugative transfer was successful for 3/5 MRSA isolates. Successful MRSA recipients carried a pSK41-like plasmid, a staphylococcal conjugative plasmid, whereas the two unsuccessful MRSA recipients did not carry pSK41. The transfer of a pSK41-like plasmid from a successful MRSA recipient to the two unsuccessful recipients resulted in conjugal transfer of the Inc18-likevanAplasmid fromE. faecalisat a frequency of 10−7/recipient CFU. In addition, conjugal transfer could be achieved for pSK41-negative MRSA in the presence of a cell-free culture filtrate fromS. aureuscarrying a pSK41-like plasmid at a frequency of 10−8/recipient CFU. These results indicated that a pSK41-like plasmid can facilitate the transfer of an Inc18-likevanAplasmid fromE. faecalistoS. aureus, possibly via an extracellular factor produced by pSK41-carrying isolates.

scholarly journals Multiple Roles for Enterococcus faecalis Glycosyltransferases in Biofilm-Associated Antibiotic Resistance, Cell Envelope Integrity, and Conjugative Transfer

2015 ◽  
Vol 59 (7) ◽  
pp. 4094-4105 ◽  
Author(s):  
Jennifer L. Dale ◽  
Julian Cagnazzo ◽  
Chi Q. Phan ◽  
Aaron M. T. Barnes ◽  
Gary M. Dunny
Keyword(s):  
Antibiotic Resistance ◽  
Enterococcus Faecalis ◽  
Cell Envelope ◽  
Opportunistic Pathogen ◽  
Growth Conditions ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Conjugative Transfer ◽  
Content Type ◽  
Resistance Determinants

ABSTRACTThe emergence of multidrug-resistant bacteria and the limited availability of new antibiotics are of increasing clinical concern. A compounding factor is the ability of microorganisms to form biofilms (communities of cells encased in a protective extracellular matrix) that are intrinsically resistant to antibiotics.Enterococcus faecalisis an opportunistic pathogen that readily forms biofilms and also has the propensity to acquire resistance determinants via horizontal gene transfer. There is intense interest in the genetic basis for intrinsic and acquired antibiotic resistance inE. faecalis, since clinical isolates exhibiting resistance to multiple antibiotics are not uncommon. We performed a genetic screen using a library of transposon (Tn) mutants to identifyE. faecalisbiofilm-associated antibiotic resistance determinants. Five Tn mutants formed wild-type biofilms in the absence of antibiotics but produced decreased biofilm biomass in the presence of antibiotic concentrations that were subinhibitory to the parent strain. Genetic determinants responsible for biofilm-associated antibiotic resistance include components of the quorum-sensing system (fsrA,fsrC, andgelE) and two glycosyltransferase (GTF) genes (epaIandepaOX). We also found that the GTFs play additional roles inE. faecalisresistance to detergent and bile salts, maintenance of cell envelope integrity, determination of cell shape, polysaccharide composition, and conjugative transfer of the pheromone-inducible plasmid pCF10. TheepaOXgene is located in a variable extended region of the enterococcal polysaccharide antigen (epa) locus. These data illustrate the importance of GTFs inE. faecalisadaptation to diverse growth conditions and suggest new targets for antimicrobial design.

scholarly journals Evolution of a 72-Kilobase Cointegrant, Conjugative Multiresistance Plasmid in Community-Associated Methicillin-Resistant Staphylococcus aureus Isolates from the Early 1990s

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Karina Yui Eto ◽  
Neville Firth ◽  
Amy M. Davis ◽  
Stephen M. Kwong ◽  
Marcelina Krysiak ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Resistance Genes ◽  
Tetracycline Resistance ◽  
Mobile Genetic Elements ◽  
Conjugative Plasmid ◽  
Penicillin Resistance ◽  
Virulence Determinants ◽  
Methicillin Resistant ◽  
Content Type ◽  
Genetic Elements

ABSTRACT Horizontal transfer of plasmids encoding antimicrobial resistance and virulence determinants has been instrumental in Staphylococcus aureus evolution, including the emergence of community-associated methicillin-resistant S. aureus (CA-MRSA). In the early 1990s, the first CA-MRSA strain isolated in Western Australia (WA), WA-5, encoded cadmium, tetracycline, and penicillin resistance genes on plasmid pWBG753 (∼30 kb). WA-5 and pWBG753 appeared only briefly in WA; however, fusidic acid resistance plasmids related to pWBG753 were also present in the first European CA-MRSA isolates at the time. Here, we characterize a 72-kb conjugative plasmid, pWBG731, present in multiresistant WA-5-like clones from the same period. pWBG731 was a cointegrant formed from pWBG753 and a pWBG749 family conjugative plasmid. pWBG731 carried mupirocin, trimethoprim, cadmium, and penicillin resistance genes. The stepwise evolution of pWBG731 likely occurred through the combined actions of IS257, IS257-dependent miniature inverted-repeat transposable elements (MITEs), and the BinL resolution system of the β-lactamase transposon Tn552. An evolutionarily intermediate ∼42-kb nonconjugative plasmid, pWBG715, possessed the same resistance genes as pWBG731 but retained an integrated copy of the small tetracycline resistance plasmid pT181. IS257 likely facilitated the replacement of pT181 with conjugation genes on pWBG731, thus enabling autonomous transfer. Like conjugative plasmid pWBG749, pWBG731 also mobilized nonconjugative plasmids carrying oriT mimics. It seems likely that pWBG731 represents the product of multiple recombination events between the WA-5 pWBG753 plasmid and other mobile genetic elements present in indigenous community-associated methicillin-sensitive S. aureus (CA-MSSA) isolates. The molecular evolution of pWBG731 saliently illustrates how diverse mobile genetic elements can together facilitate rapid accrual and horizontal dissemination of multiresistance in S. aureus CA-MRSA.

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