Staphylococcus aureus is a major opportunistic pathogen causing a wide range of infections in humans and animals. Methicillin-resistant S. aureus (MRSA) has traditionally been regarded as a strictly human problem, initially confined to the healthcare settings and later a matter of concern in the general community too. All this changed in 2005 with the isolation of a specific MRSA clone, assigned to Clonal Complex (CC)398, from pigs and pig farmers in the Netherlands. These findings triggered worldwide investigation, showing the presence of this livestock-associated (LA)-MRSA clone in a variety of farm animals and in persons in contact with affected animals. Furthermore, the capacity of LA-MRSA CC398 to cause infections in humans and animals has been well documented. Recently, MRSA with a divergent mecA-homologue gene variant has been discovered in bovines and humans. Together, these emerging MRSA strains from animal sources have raised new questions as to their origin and inter-host transmission, as well as raised global concern in both veterinary and human medicine about health risks posed by MRSA prevailing in livestock.<p>In the present work, we aimed to investigate the extent and molecular epidemiology of the LA-MRSA reservoir in animal and human populations, including on livestock farms and in acute-care hospitals in Belgium. As a secondary objective, the presence of methicillin susceptible S. aureus (MSSA) CC398, from which MRSA CC398 could locally emerge by acquisition of the Staphylococal Cassette Chromosome mec (SCCmec) element, was assessed. To this end, we undertook an extensive and systematic cross-sectional survey of S.aureus and MRSA carriage among humans and animals on pig, veal calf, dairy cattle, beef cattle, broiler and horticulture farms. A questionnaire, completed by all farm residents, was used to assess occupational risk factors for human MRSA CC398 carriage. Bacterial genetic characterisation was done by spa typing, SCCmec typing and multi-locus sequence typing (MLST). Antimicrobial susceptibility profiles were determined; the presence of resistance genes and toxin genes were determined by PCR. A second set of S. aureus clinical isolates from two national surveys organised in 2005 and 2008 were characterised using the same methods.<p>Carriage of MRSA CC398 was highly prevalent in animals and humans on pig and veal calf farms and to a significantly lesser extent on beef, dairy, broiler and horticulture farms (Chapter 5.1). Persons who work with pigs or veal calves on a daily basis are at significantly higher risk for MRSA CC398 carriage compared to farm-exposed persons who work with them less regularly or never. In accordance with the results from the present work as well as those from others, it appears important to assess the impact of interventions at farm-level that aim to reduce the MRSA carriage rate in animals, as this would also reduce the risk for MRSA carriage in farmers and relatives.<p> MRSA CC398 isolates, especially those from veal calf farms, were frequently multi-resistant and thereby represent a reservoir of antimicrobial resistance determinants that could be transferred to other, more human-adapted staphylococci or other micro-organisms (Chapter 5.1). Additionally, this multi-resistance phenotype should be considered when applying empiric treatment of human staphylococcal infections in livestock-exposed persons. Only very few major “human-associated” virulence factors were detected, indicating a limited virulence capacity of LA-MRSA CC398 isolates. MRSA strains with the mecA homologue mecC, which is difficult to detect using conventional diagnostic methods, were found in beef and dairy cattle, but not in humans. <p>MSSA CC398 strains from which MRSA CC398 might locally emerge were frequently detected in humans and animals on pig, veal and broiler farms, all of which are commonly known to be affected by MRSA CC398 (Chapter 5.2). Three porcine MSSA CC398-t011 isolates harbored remnant DNA of a composite SCCmec V(5C2&5)c element, from which the mec gene complex was lacking. These findings indicate that the strains were previously involved in SCCmec recombination events. Processes similar to the one described here likely contribute to the enormous diversity of SCCmec elements observed in staphylococci. <p>Although LA-MRSA CC398 strains were frequently detected in livestock and livestock-exposed persons, they only represented a minority (~1%) of the MRSA strains from hospitalised patients. This suggests that this specific MRSA clone has not yet spread among Belgian patients without livestock contact (Chapter 5.3). However, similar to what has been seen in other countries, we observed a recent emergence of severe infections, caused by a human-adapted subclone of MSSA CC398, in hospitalised patients without livestock contact (Chapter 5.4). <p>Once more has S. aureus proven its versatility: it has optimally adapted to the selective pressure exerted by intensive animal farming by acquisition of mobile genetic elements, such as resistance determinants. Clearly MRSA is no longer a strictly human problem. Working across the human and veterinary health sectors will be essential to tackle the dissemination and pathogenic evolution of MRSA in livestock. <p> / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished
| Identifer | oai:union.ndltd.org:ulb.ac.be/oai:dipot.ulb.ac.be:2013/209576 |
| Date | 13 December 2012 |
| Creators | Vandendriessche, Stien |
| Contributors | Denis, Olivier, Haesebrouck, Freddy, Struelens, Marc, Gevenois, Pierre-Alain, Dewulf, Jeroen, Kluytmans, Jan, Maes, Dominiek, Vandenberg, Olivier, Butaye, Patrick, Abramowicz, Marc, Catry, Boudewijn |
| Publisher | Universite Libre de Bruxelles, Université libre de Bruxelles, Faculté de Médecine – Sciences biomédicales, Bruxelles |
| Source Sets | Université libre de Bruxelles |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis, info:ulb-repo/semantics/doctoralThesis, info:ulb-repo/semantics/openurl/vlink-dissertation |
| Format | 1 v., 3 full-text file(s): application/pdf | application/pdf | application/pdf |
| Rights | 3 full-text file(s): info:eu-repo/semantics/closedAccess | info:eu-repo/semantics/openAccess | info:eu-repo/semantics/openAccess |
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