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CONtrol of COmmunity-acquired MRSA: Rationale and Development of counteractions

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Understanding the genetics of 'superbug' strains

Until recently, methicillin-resistant Staphylococcus aureus (MRSA) strains were confined to hospitals (HA-MRSA). The emergence of community and farm MRSA strains has triggered scientists to investigate the mechanisms underlying the ecological success of S. aureus.

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The first epidemics of MRSA in patients without prior history of hospitalisations were described in the 1990s. Since then, community- and farm-associated MRSA (CA-MRSA and FA-MRSA, respectively) have developed as an important cause of infections. MRSA isolates carry the methicillin resistance mecA gene on a chromosome cassette also referred to as SCCmec. From a genetic perspective, most HA-MRSA types belong to clonal complex 5, while CA-MRSA is genetically much more diverse. The successful establishment of CA-MRSA in the community constitutes the most alarming change in the epidemiology of MRSA. It is, therefore, of paramount importance to understand the implicated mechanisms involved to be able to manage or prevent bacterial infection. Based on this, the EU-funded 'Control of community-acquired MRSA: Rationale and development of counteractions' (CONCORD) project aimed to investigate CA-MRSA colonisation. To this end, the consortium concentrated on the genetic and transcriptional differences among MRSA strains in Europe, and assessed how they could influence bacteria physiology. Following the collection and molecular typing of a large set of European MRSA isolates, researchers concluded that some resistant bacteria types originated in Europe, while others were imported. Interestingly, the majority of these strains demonstrated resistance to other antibiotics and livestock-associated (LA) MRSA strains showed additional resistance to zinc, a property attributed to the csrC gene. Dissemination studies revealed a reciprocal dissemination pattern between humans and animals, which, however, occurred at a very low rate. Scientists also tested the hypothesis that small changes in the genetic content of S. aureus might lead to physiological differences and found that alteration of the beta-toxin gene affected host adaptation. High antibiotic pressure was found to have driven ribosomal RNA loss in HA-MRSA and cystic fibrosis isolates. Scientists believe that although these events facilitated resistance development, they reduced the fitness of the strains and their subsequent success in the community. In contrast, CA-MRSA retained their rRNA copies and were therefore more fit and capable of spreading in the community. Through novel mathematical models, CONCORD researchers generated the opportunity to study between-farm and between-hospital MRSA transmissions. These tools could be employed by countries to estimate the transmission potential of MRSA strains, assess public and livestock risk and take appropriate countermeasures.

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