Detection of Mobile-Genetic-Element Variation between Colonizing and Infecting Hospital-Associated Methicillin-Resistant Staphylococcus aureus Isolates
ABSTRACT Whole-genome analysis by 62-strain microarray showed variation in resistance and virulence genes on mobile genetic elements (MGEs) between 40 isolates of methicillin-resistant Staphylococcus aureus (MRSA) strain CC22-SCCmecIV but also showed (i) detection of two previously unrecognized MRSA transmission events and (ii) that 7/8 patients were infected with a variant of their own colonizing isolate.
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ABSTRACT: Successful meticillin-resistant Staphylococcus aureus (MRSA) clones have evolved to adapt to healthcare, community and livestock environments. This review will bring together recent studies into clone adaptation and the importance of genes acquired during horizontal gene transfer to survival in specific environments. It will also discuss the role of global regulators controlling virulence gene expression and resistance to antibiotics, such as the agr and vraRS systems. Understanding these processes in successful clones could reveal novel targets for therapeutic agents, which are urgently required to reduce the infection burden and improve treatment options.06/2014; DOI:10.1016/j.jgar.2014.02.003
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ABSTRACT: Many pathogenic bacteria have bacteriophage and other mobile genetic elements whose activity during human infections has not been evaluated. We investigated the gene expression patterns in human subjects with invasive Methicillin Resistant Staphylococcus aureus (MRSA) infections to determine the gene expression of bacteriophage and other mobile genetic elements. We developed an ex vivo technique that involved direct inoculation of blood from subjects with invasive bloodstream infections into culture media to reduce any potential laboratory adaptation. We compared ex vivo to in vitro profiles from 10 human subjects to determine MRSA gene expression in blood. Using RNA sequencing, we found that there were distinct and significant differences between ex vivo and in vitro MRSA gene expression profiles. Among the major differences between ex vivo and in vitro gene expression were virulence/disease/defense and mobile elements. While transposons were expressed at higher levels ex vivo, lysogenic bacteriophage had significantly higher in vitro expression. Five subjects had MRSA with bacteriophage that were inhibited by the presence of blood in the media, supporting that the lysogeny state was preferred in human blood. Some of the phage produced also had reduced infectivity, further supporting that phage were inhibited by blood. By comparing the gene expression cultured in media with and without the blood of patients, we gain insights into the specific adaptations made by MRSA and its bacteriophage to life in the human bloodstream.Frontiers in Microbiology 03/2015; · 3.94 Impact Factor
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ABSTRACT: Staphylococcus aureus is a commensal and major pathogen of humans and animals. Comparative genomics of S. aureus populations suggests colonization of different host species is associated with carriage of mobile genetic elements (MGE), particularly bacteriophages and plasmids capable of encoding virulence, resistance and immune evasion pathways. Antimicrobial resistant S. aureus of livestock are a potential zoonotic threat to human health if they adapt to colonize humans efficiently. We utilized the technique of experimental evolution and co-colonized gnotobiotic piglets with both human- and pig-associated variants of the lineage clonal complex (CC)398, and investigated growth and genetic changes over 16 days using whole genome sequencing. The human isolate survived co-colonization on piglets more efficiently than in vitro. During co-colonization, transfer of MGEs from the pig to the human isolate was detected within 4 hours. Extensive and repeated transfer of two bacteriophages and three plasmids resulted in colonization with isolates carrying a wide variety of mobilomes. Whole genome sequencing of progeny bacteria revealed no acquisition of core genome polymorphisms, highlighting the importance of MGEs. S. aureus bacteriophage recombination and integration into novel sites was detected experimentally for the first time. During colonisation, clones co-existed and diversified rather than a single variant dominating. Unexpectedly, each piglet carried unique populations of bacterial variants, suggesting limited transmission of bacteria between piglets once colonized. Our data show that HGT occurs at very high frequency in vivo and significantly higher than that detectable in vitro..Genome Biology and Evolution 09/2014; DOI:10.1093/gbe/evu214 · 4.53 Impact Factor