CONCORD

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

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 Obiettivo del progetto (Objective)

'Until recently, methicillin-resistant Staphylococcus aureus (MRSA) were confined to hospitals (HA-MRSA). However, community- and farm-associated MRSA (CA-and FA-MRSA) has developed as an important cause of infections. No strategies exist to combat these MRSA. CONCORD is aimed at explaining the ecological success in the community and the farm environment of CA- and FA-MRSA in contrast to HA-MRSA in order to facilitate the rationale and development of effective strategies against CA- and FA-MRSA. Epidemiology of CA-MRSA is complex and incomplete. To obtain both a more complete description of the epidemiology of CA-MRSA and recent isolates small scale surveillance will be performed among patients in the 20 most populous EU countries, pig farms in major pig exporting countries and important veal calve raising countries. Genomics data for CA-MRSA are limited and non-existent for FA-MRSA. Successful adaptation of MRSA to a new environment supposes either the acquisition of novel properties or the differential expression of genes already present. Only 2 CA-MRSA have been fully sequenced and the UMCU has sequenced a FA-MRSA. Whole genome sequencing, comparative genome hybridization and transcriptomics will be used to understand the genetic adaptations of MRSA in the community. The contribution of putative virulence factors to pathogenicity will be studied by knock-outs and complemented strains of these knock-outs. The strains will be tested in in vitro and ex vivo models to establish their physiological role. Mathematical modelling is an important tool to manage infection control. A few models exist that evaluate measures to reduce transmission of HA-MRSA or CA-MRSA in jails. No models are available for FA-MRSA. Modelling will provide both fundamental insights on MRSA epidemiology as well as specific recommendations or testable hypotheses for human and veterinary clinical practice. The potential of intervention strategies to combat CA- and FA-MRSA will be determined.'

Introduzione (Teaser)

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.

Descrizione progetto (Article)

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.