Detection of Mobile-Genetic-Element Variation between Colonizing and Infecting Hospital-Associated Methicillin-Resistant Staphylococcus aureus Isolates

Centre for Infection, Division of Clinical Sciences, St George’s University of London, London, United Kingdom.
Journal of clinical microbiology (Impact Factor: 3.99). 12/2011; 50(3):1073-5. DOI: 10.1128/JCM.05938-11
Source: PubMed


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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Available from: Jodi A Lindsay,
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    • "ssor genes was indicative of the expression of the phage lytic module . We were unable to place the MRSA genomes into lineage groups ( Lindsay et al . , 2006 ; McCarthy and Lindsay , 2010 ) based on the presence / absence of mobile genetic elements because the heterogeneity in gene expression and the potential for prior horizontal gene transfers ( McCarthy et al . , 2012a , b ) could have led to erroneous results ."
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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; 6. DOI:10.3389/fmicb.2015.00216 · 3.99 Impact Factor
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    • "The movement of SCCmec elements and ermC plasmids has been highlighted, showing each move at different rates and into and out of sections of the tree, potentially contributing to selection in different environments. Whole genome microarray studies support this amount of MGE variation, and show that even within a single hospital at a single time point, substantial variation in MGE content is typical of this clone (McCarthy et al., 2012a,b; Lindsay et al., 2012). Expansion of this clone has also been associated with acquisition of resistance to a wide range of additional antibiotics (Knight et al., 2012). "
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    ABSTRACT: Investigation of S. aureus outbreaks, and particularly those due to methicillin-resistant S. aureus (MRSA) in hospitals, can identify infection reservoirs and prevent further colonization and infection. During outbreaks, S. aureus genomes develop single nucleotide polymorphisms (SNPs), small genetic rearrangements, and/or acquire and lose mobile genetic elements (MGE) encoding resistance and virulence genes. Whole genome sequencing (WGS) is the most powerful method for discriminating between related isolates and deciding which are involved in an outbreak. Isolates with only minor variations are detectable and can identify MRSA transmission routes and identify reservoirs. Some patients may carry 'clouds' of related isolates, and this has consequences for how we interpret the data from outbreak investigations. Different clones of MRSA are evolving at different rates, influencing their typability. S. aureus genome variation reveals the importance of antibiotic resistance in the long term evolution of successful hospital clones, contributing to strategies to prevent the spread of successful MRSA clones.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 05/2013; 21. DOI:10.1016/j.meegid.2013.04.017 · 3.02 Impact Factor
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    • "Fluoroquinolones probably select for successful HA-MRSA colonization in hospital patients. The major reservoir of infecting HA-MRSA in healthcare is colonized patients, with most infections due to the patient's own colonizing strain (McCarthy et al., 2012a). Many patients are prescribed antibiotics for a variety of reasons, including prophylaxis, empirical therapy or for treatment of a range of infections. "
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    ABSTRACT: In many parts of the world, MRSA are responsible for a high proportion of S. aureus infections in patients in contact with healthcare. Molecular studies have shown this is due to one or more MRSA clones that have become endemic in each hospital or healthcare facility, resulting in hospital- or healthcare-associated MRSA (HA-MRSA). The infection rate and clones responsible for HA-MRSA can vary substantially in different geographical locations. Molecular methods have allowed clones to be categorized, as well as the opportunity to track the evolution and spread of clones in healthcare settings and around the world. The genomes of HA-MRSA isolates belonging to the same clonal group can show dramatic variability particularly in the carriage of mobile genetic elements (MGEs) encoding virulence and resistance genes. HA-MRSA are potentially resistant to all classes of antibiotics, although individual isolates that are fully drug resistant are not reported. The incidence of fluoroquinolone resistance in HA-MRSA is remarkably high, suggesting use of this class of antibiotics as well as the β-lactams contributes to the selection and success of HA-MRSA clones in the hospital setting.
    International journal of medical microbiology: IJMM 03/2013; 303(6-7). DOI:10.1016/j.ijmm.2013.02.005 · 3.61 Impact Factor
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