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Veterinary Microbiology journal homepage: www.elsevier.com/locate/vetmic

MRSA in equine hospitals and its significance for infections in humans Christiane Cuny* , Wolfgang Witte Robert Koch Institute, Wernigerode Branch Burgstrasse, 3738855 Wernigerode, Germany

A R T I C L E I N F O

A B S T R A C T

Article history: Received 26 October 2015 Received in revised form 13 January 2016 Accepted 16 January 2016

MRSA infections in equine clinics were reported from Northern America, Europe, Australia, and Japan. The majority of nosocomial infections in horses is obviously associated with particular MRSA clonal lineages. As already observed for epidemic MRSA in human hospitals more than 10 years ago, a dynamics of MRSA clonal lineages is also observed in European equine clinics: clonal lineages belonging to clonal complex (CC) 8 are on the retreat whereas MRSA attributed to CC398 become increasingly prevalent. The majority of CC398 isolates belong to a subpopulation which is particularly associated with equine hospitals as indicated by molecular typing. When emerging in equine clinics, MRSA from horses were also found as nasal colonizers of veterinary personnel. MRSA exhibiting the typing characteristics of MRSA known from equine clinics are obviously rare among MRSA from infections in humans. Although rare so far epidemic MRSA from human hospitals (HA-MRSA, e.g., ST22, ST225) have been isolated from nosocomial infections in horses and need particular attention in further surveillance. ã 2016 Published by Elsevier B.V.

Keywords: MRSA Equine clinics Zoonotic MRSA infection

1. Introduction Staphylococcus aureus colonizes asymptomatically the anterior nares of about 30% of humans; dependent of predispositions on side of the host it can cause a diverse spectrum of diseases ranging from relatively minor skin and wound infections to serious and life-threatening infections such as endocarditis, pneumonia, and sepsis. During the last 50 years the development of antibiotic resistance became a matter of concern. This applies in particular to methicillin-resistant S. aureus (MRSA) that is resistant to nearly all b-lactam antibiotics and often additionally resistant against antibiotic classes other than beta lactams (Witte et al., 2008). Studies on dissemination of MRSA are based on molecular typing (for review of the methods see (Palavecino, 2014)). As the population structure of S. aureus is mainly clonal, multi locus sequence typing (MLST) resulting in sequence types (ST) and clonal complexes (CC) provides a robust framework for tracing the evolutionary origin and spread of MRSA. Spa typing, which is based on sequence polymorphisms of the spa gene, is used worldwide as a first-line typing tool. Although there are cases of homoplasy, spatypes can be attributed to clonal complexes. It has replaced SmaI generated macrorestriction pattern analysis (“PFGE”) in routine typing in many laboratories. The mec genes conferring methicillin resistance are contained by SCCmec elements of which at least 11 different types were described so far. Typing of them can give

* Corresponding author. Fax: +49 18752203. E-mail address: [email protected] (C. Cuny).

further information about the evolutionary background if they are different for isolates exhibiting the same spa type and attributed to the same ST. Typing results are usually represented as CC/ST, spatype and SCCmec type, e.g., ST8, t064, IV. Recently, progress in next generation sequencing has made the rapid and affordable analysis of whole bacterial genomes possible and has facilitated much deeper and more precise insight into the evolution and dissemination of MRSA (Harrison et al., 2014). MRSA was originally a nosocomial pathogen (hospital-associated MRSA, HA-MRSA), later on MRSA infections among previously healthy individuals in the community, without links to healthcare settings, emerged in the 1990s. The causative pathogens were referred to as communityassociated MRSA (CA-MRSA). As indicated by molecular typing, in most cases HA-MRSA and CA-MRSA evolved independently of each other and differ by genomic traits (Witte et al., 2008). The epidemiological distinction can be blurred, as mutual exchange of strains assigned to HA-MRSA or LA-MRSA between these settings is increasingly recognized (Espadinha et al., 2013). MRSA infections in the community also can be caused by livestock associated MRSA (LA-MRSA). LA-MRSA is initially associated with livestock, it differs from genotypic HA-MRSA and genotypic CA-MRSA by genomic traits (Cuny et al., 2010; Price et al., 2012). S. aureus, including MRSA, can colonize and also cause a variety of infections in a wide range of host species including livestock, wildlife, and companion animals. Although an original animal reservoir is likely for particular STs and CCs, they seem to be less host specific and capable to affect different animal species, humans included (for summary see Cuny et al., 2010). MRSA in animals

http://dx.doi.org/10.1016/j.vetmic.2016.01.013 0378-1135/ ã 2016 Published by Elsevier B.V.

Please cite this article in press as: C. Cuny, W. Witte, MRSA in equine hospitals and its significance for infections in humans, Vet. Microbiol. (2016), http://dx.doi.org/10.1016/j.vetmic.2016.01.013

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belonging to these CCs can act as a reservoir for zoonotic infection of humans besides their impact on animal welfare. In particular livestock associated (LA) MRSA which are attributed to CC 398 is abundant among various livestock as well as companion animals in Europe, Northern America, China (Pantosti, 2011). Furthermore, infections of humans with LA-MRSA CC398 reflect its low host specificity (Köck et al., 2013). S. aureus, in particular MRSA is able to cause a variety of infection in horses such as skin and soft tissue MRSA infections, bacteraemia, septic arthritis, osteomyelitis, implant-related infections, metritis, omphalitis, catheter-related infections and pneumonia (Anderson et al., 2009). The question of transmission of MRSA from horses to humans is of particular interest as horse riding became popular during the past decades. There are about 1,2 millions of horses in Germany and 30000 to 40000 riding accidents are recorded per year (https://pferdundreiter.wordpress.com/2011/02/01/%E2%80%9E30-000-pferdeunfalle-in-d-pro-jahr/). Nasal MRSA carriage is a major risk factor for surgical site infections with MRSA in humans (Fierobe et al., 1999). Nosocomial MRSA infections in horses were reported for the first time in 1997 from the USA (Hartmann et al., 1997) and from Japan (Shimizu et al., 1997). This was followed by a report on the emergence of MRSA in horses and nasal colonization of veterinary personnel from a North Carolina veterinary teaching hospital in 1999 (Seguin et al., 1999). Because of identical SmaI macrorestriction patterns of isolates from horses and from humans attending them and because of the time course a human origin was presumed, a link to MRSA of human nosocomial origin was not established. In the following we group reports on emergence and spread of MRSA by their typing patterns. 2. MRSA ST8, t064, IV in horses The multiresistance phenotype of these isolates usually includes gentamicin. The above cited description of a cluster of MRSA infections in horses in the USA (Seguin et al., 1999) was followed by a report on MRSA in a Canadian veterinary teaching hospital and its transmission to humans attending horses (Weese, 2004). The finding of an overall rate of community-associated colonization in 27 per 1,000 admissions of horses suggested dissemination outside the clinical setting in Ontario Federal state (Weese et al., 2006a). There was, however, obviously no dissemination of MRSA among horses at farms located in geographical areas of Atlantic Canada such as New Brunswick, Nova Scotia, Prince Edward Island, and Newfoundland (Burton et al., 2008). Typing by means of SmaI macrorestriction profile analysis attributed these MRSA to the Canadian epidemic MRSA lineage CMRSA-5. Further molecular typing resulted in the typing pattern ST8, spa type t064, SCCmecIV (Weese et al., 2005, 2006a). The proportion of CMRSA-5 among MRSA from nosocomial infections in humans in Canada at the end of the 1990ties was 20%, it afterwards declined to 5% at maximum (Christianson et al., 2007). Because of the typing characteristics a human hospital origin was assumed (Fig. 1). It seems likely that MRSA ST8, t0064, IV was introduced into a veterinary hospital and later on spread among different equine clinics. As shown later on (Anderson et al., 2009), there was further spread within and between several veterinary teaching hospitals in the Quebec and Ontario provinces. This MRSA strain was also detected in 1,2% of horses admitted to veterinary hospitals in Saskatchewan, Alberta, and British Columbia (Tokateloff et al., 2009). That it is still present in Canadian veterinary hospitals is indicated by its isolation from an infection in a neonatal alpaca (Stull et al., 2012). Furthermore, MRSA exhibiting ST8, t064, SCCmecIV, and gentamicin resistance was reported for infections in horses in veterinary hospitals in the upper Midwest and Northeast

of the USA (Lin et al., 2011). According to their PFGE patterns and possession of SCCmecIV isolates from a veterinary teaching hospital in Ohio can also be attributed to this strain (Van Balen et al., 2014). In Europe, MRSA ST8, t064, IV was reported at first time from infections in a veterinary hospital attending horses in Ireland (O’Mahony et al., 2005). When MRSA isolates from two clusters of MRSA infections in horses in 2006/2007 were typed at a Veterinary Microbiological Diagnostic Center in the Netherlands, isolates exhibiting spa-type t064 predominated among isolates from the first cluster. However, 16 of the 17 isolates from the second cluster were attributed to CC398 (spa-types t011 and t1223), only one isolates exhibited t064 (Van Duijkeren et al., 2010). MRSA ST8, t064, IV was also observed in Australia among MRSA from infections in horses (Axon et al., 2011). In a recent study in Germany 2.2% of isolates from nosocomial MRSA infections in horses exhibited ST8,t064, SCCmecIV, and resistance to gentamicin (Cuny et al., 2016). 3. MRSA ST8, t064, IV in humans Demonstration of nasal colonization of humans attending horses with MRSA infections in Canadian equine clinics led to the fear of infections in humans exposed to infected animals. This was indeed observed when an outbreak of MRSA infections occurred among in humans who worked with a colonized neonatal foal (Weese et al., 2006b). The proportion of MRSA ST8, t064, SCCmecIV among all MRSA from infections in humans in northern American hospitals seems to be low: 0.7% for isolates from a medical center in Chicago (David et al., 2013), a slightly higher proportion was reported from three hospitals in the Bronx (Varshney et al., 2009). MRSA ST8, t064, IV was also observed as nasal colonizer of humans attending hospitalized horses in Ireland (O’Mahoney et al., 2005). According to Kinnevey et al. (2014) its recent proportion among a sample of isolates from sporadic nosocomial MRSA infections in Irish hospitals was about 1%. In Germany, only 0.05% among 10864 MRSA isolates from infections in humans collected from 2006 until 2014 exhibited typing pattern ST8, t064, IV (Cuny et al., 2016). Nosocomial infections with MRSA are impressively rare in the Netherlands. Only four among 943 S. aureus isolates from intensive care unit (ICU) patients from 14 hospitals isolated from 1996 until 2006 were MRSA, and included spa-type t064 (Rijnders et al., 2009). Also in Australia MRSA ST8, t064, IV is also observed among isolates from nasal colonization of veterinarians (Jordan et al., 2011) and from infections in humans in the community (Coombs et al., 2011). 4. MRSA ST254, t009/t036, IV in horses In the mid of the 2000’s clusters of nosocomial MRSA infections were recorded in veterinary hospitals attending horses in Central Europe (Friedrich et al., 2004; Cuny et al., 2006). Nearly all of the corresponding isolates exhibited spa type t036 which attributed them to CC8, ST254. Furthermore, MRSA ST254, t009, IV became known from infections in horses in Germany (Walther et al., 2009) where it is still present, although at a lower proportion as previously observed (Vince et al., 2014; Cuny et al., 2016). ST254 is a single locus variant of ST8. Spa type t036 differs from spa type t009 by a large deletion comprising 4 repeats, and both differ from t008 by several genetic events (http://spa.ridom.de/spatypes.shtm). Both spa types were so far only detected in S. aureus attributed to ST254 (http://spa.ridom.de/spatypes.shtml) and therefore allow an unrestrained attribution of isolates to this clonal lineage. MRSA with this pattern was also observed in horses in a Dublin veterinary hospital (Moodley et al., 2006).

Please cite this article in press as: C. Cuny, W. Witte, MRSA in equine hospitals and its significance for infections in humans, Vet. Microbiol. (2016), http://dx.doi.org/10.1016/j.vetmic.2016.01.013

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5. MRSA ST254, t009/t036, IV in humans To our knowledge MRSA ST254 from infections in humans are only known from Europe so far, namely from the United Kingdom (Robinson and Enright, 2003) from Germany (Witte et al., 2008), and more recently from Poland (Mlynarczyk et al., 2014). In the UK MRSA ST254 have obviously evolved at least two times, one time by acquisition of SCCmecI and another time as “EMRSA-10” by acquisition of SCCmecIV (Robinson and Enright, 2003). In Germany MRSA ST254 was particularly prevalent in human hospitals in the Lower Saxony (LS) federal state until the end of the 1990ties and declined afterwards as they already did in the UK before. We can‘t exclude that they were introduced to Germany by the British army which had still bases in LS at this time. MRSA ST254, t036, IV of horse origin differ from those from infections in humans by loss of the IEC (Walther et al., 2009). MRSA with spa type t036 were not detected among a sample of isolates from infections in humans in Germany sent to the German Reference Center for typing so far (10864 isolates from 2006 until 2014). In Austria one case only became known so far (Krziwanek et al., 2008). 6. Other MRSA from horses attributed to clonal complex CC8 The occurrence of MRSA ST247, t051, IV in horses (Cuny et al., 2016) was at first glance surprising as MRSA ST247,t051 are known as an epidemic HA-MRSA which was widely disseminated in a number of European countries in the 1990ties (Witte et al., 2008). As this HA-MRSA contains SCCmecI, a relation to the recent isolates from horses is unlikely. 7. MRSA ST398, t011/t6867, IV in horses Livestock-associated methicillin resistant S. aureus (LA-MRSA), in particular clonal complex CC398, is widely disseminated as colonizer of various livestock (Graveland et al., 2011). A phylogenetic analysis of genome-wide single nucleotide polymorphisms (SNPs) of S. aureus/MRSA CC398 of human and animal origin discriminated between an ancestral human-adapted subpopulation and a subpopulation that is associated with animals (mainly livestock) and evolved from the methicillin-susceptible human associated subpopulation (Price et al., 2012). The isolation of MRSA CC398 from nosocomial infections in horses was first reported for an Austrian university veterinary hospital (Cuny et al., 2008) where it became the most prevalent clonal lineage afterwards (Loncaric et al., 2013). The decline of MRSA CC8 and their replacement by MRSA CC398 in equine clinics which was also observed by in the Netherlands (Van Duijkeren et al., 2010) and in Germany (Vince et al., 2014; Cuny et al., 2016). The emergence of MRSA CC398 as a nosocomial pathogen in equine clinics was furthermore reported from Belgium (Van den Eede et al., 2009), from Switzerland (Sieber et al., 2011), and from Spain (Gómez-Sanz et al., 2014). MRSA CC398 from horse clinics exhibit a typical pattern of characteristics when subjected to typing, spa types t011, and more rarely t6867, SCCmecIV, and phenotypic resistance to gentamicin based on the aacA-aphD gene (Cuny et al., 2008; Van Duijkeren et al., 2010). A more detailed analysis of the population structure through mutation discovery (single nucleotide polymorphisms, SNP’s) at 97 loci revealed that MRSA CC398 from horse clinics which exhibit the above mentioned characteristics represent a particular sub-clone (“equine clinic clade”, (Abdelbary et al., 2014)). Therefore MRSA CC398 associated with equine clinics can be differentiated from other MRSA of CC398 by means of canonical SNP‘s. A recent study on 272 MRSA isolates from horses from 17 equine hospitals and from 39 large animal practices all over Germany attributed 67% to the equine clinic

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associated clade of CC398, 16% also belonged to CC398 but were not attributed to this clade, and 17% of the isolates were attributed to other CCs (Cuny et al., 2016). The observation of MRSA CC398 which is attributed to the livestock subpopulation but not to the equine clinics associated clade raises the question of the origin. Most likely is the acquisition from veterinarians caring for both, livestock and horses.This can be mediated by both, (i) animal to animal transmission as e.g., by insufficiently disinfected hands of veterinarians and veterinary personnel and (ii) transmission from nasal colonization of humans caring for horses. 8. MRSA ST398, t011/t6867, IV in humans MRSA CC398 is a frequent colonizer of humans with occupational exposure to livestock (for review, see Cuny et al., 2013), as well as of veterinary personnel working in equine clinics (Cuny et al., 2008; Van Duijkeren et al., 2010; Van den Eede et al., 2013; Cuny et al., 2016). Although dissemination of LA-MRSA CC398 among the community seems to be rare so far, infections in humans without animal contact suggest human to human transmission (Deiters et al., 2015). LA-MRSA CC398 has also been demonstrated as a causative agent of infections in humans, in particular those affecting skin and soft tissue as well as septicemia and ventilator-associated pneumonia in hospitalized patients in many countries (Pantosti, 2012). Infections in humans with LAMRSA CC398 is significantly more frequent in a geographical area of Germany at which the density of conventional livestock farm is particularly high (>11% of all MRSA blood culture isolates from humans, (Cuny et al., 2015b)). A recent study, which was based on a substantial number of isolates typed at the German reference Centre for Staphylococci and Enterococci, revealed that the proportion of MRSA CC398 isolates that exhibit the typing characteristics of the equine clinic associated clade among all MRSA from infections in humans was very low (0,14%, (Cuny et al., 2016). The equine clinics associated MRSA is, however, also very rare among isolates from nasal colonization of humans (Cuny et al., 2016). Therefore its low proportion among MRSA from infections is rather likely due to limited dissemination outside veterinary hospitals. A study addressing this question is in progress. As reported previously (Cuny et al., 2015a) the IEC that is typical for S. aureus from humans was also detected in several isolates of this subpopulation originating from infections in horses and from nasal carriage veterinary personnel in equine clinics. This finding suggests reacquisition of traits relevant for readaptation to the human host. Possession of the IEC is not a prerequisite to the capability of LA-MRSA CC398 to cause infections in humans. It remains to be shown whether it supports permanent nasal colonization of humans. Of particular interest is the finding of isolates from horses which contain sea in addition to the immediate immune evasion associated genes (Cuny et al., 2015a) as consumption of horse meat is common in some countries. So far enterotoxin genes seem to be rare in MRSA CC 398 (Argudín et al., 2011), and food intoxications associated with S. aureus attributed to CC398 were not reported so far. 9. MRSA CC/ST1, t127, IV in horses MRSA attributed to clonal lineage ST1 (not containing luk-PV) was for the first time observed in an Austrian veterinary hospital in 2007 (Cuny et al., 2008) where it is still present (Loncaric et al., 2014). Later on it was reported from a Swiss university veterinary hospital (Sieber et al., 2011). It represented only 0,37% of MRSA isolates from horses in a recent study in Germany (Cuny et al., 2016).

Please cite this article in press as: C. Cuny, W. Witte, MRSA in equine hospitals and its significance for infections in humans, Vet. Microbiol. (2016), http://dx.doi.org/10.1016/j.vetmic.2016.01.013

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10. MRSA CC/ST1, t127, IV in humans and in other animal species Like MRA CC398, MRSA attributed to CC1 seems to have low host specificity. It has been identified from infections in humans in many countries and is particularly prevalent among isolates from nosocomial infections in Romania (Grundmann et al., 2014). CAMRSA CC1 containing luk-PV were particularly prevalent in the USA and are reported from sources worldwide (Witte, 2008). Furthermore, MRSA CC1 was identified as colonizer of farmed pigs and cattle. It seems to be prevalent in Italy and less frequent in other European countries (Alba et al., 2015). The high genetic relatedness of isolates from Italian cattle herds and humans in relation to typing characteristics and possession of virulenceassociated genes is of particular interest (Alba et al., 2015). Because of these findings several origins of MRSA CC1 in equine clinics and dissemination from horses cannot be excluded. Mutual transmission between humans and animal species has to be taken into consideration. 11. Emergence of MRSA CC/ST22 and ST225 in equine clinics Although detected at low frequencies among MRSA from nosocomial infections in horses so far, MRSA which were attributed to CC22 in Germany (Cuny et al., 2016) and to ST225 in Austria (Loncaric et al., 2014) are of concern. MRSA attributed to CC22 or to ST225 are predominant among isolates from human hospitals in Germany (Layer et al., 2012) and on the rise in other European countries (Grundmann et al., 2014). Transmission of

MRSA CC22 between humans and animals under veterinary care is well documented by genome based typing (Harrsison et al., 2014). Further establishing of both hospital associated MRSA clones in equine clinics would create an additional reservoir. 12. Emergence of MRSA CC130 in an equine clinic A novel LA-MRSA attributed to clonal complex 131 and containing the mecC gene was first described in the UK and Denmark from cattle. Meanwhile it became known from a number of other animal species and from infections in humans. The animal origin of the human isolates was shown by means of genome based phylogeny (Harrison et al., 2013). An isolate ST130 containing mecC from an infection in a horse was recently detected in Germany (Cuny et al., 2016). 13. Conclusions MRSA that emerged in equine clinics can be of human hospital origin or evolved from livestock associated MRSA. This was followed by wide dissemination between veterinary hospitals (Fig. 1). According to the data available so far, equine clinics seem not to present a substantial reservoir for MRSA infections in humans. Transmission of MRSA from horses can concern both, humans with occupational exposure and humans caring for horses “at home”. Nasal colonization was reported for 13.7% of veterinarians and veterinary personnel of an Austrian university veterinary hospital

Fig. 1. Emergence and spread of MRSA of primary hospital origin (ST8, ST22 and ST5) and of livestock origin (ST398) in equine clinics.

Please cite this article in press as: C. Cuny, W. Witte, MRSA in equine hospitals and its significance for infections in humans, Vet. Microbiol. (2016), http://dx.doi.org/10.1016/j.vetmic.2016.01.013

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(Cuny et al., 2008), for 9.4% of two Dutch veterinary hospitals (Van Duijkeren et al., 2010), up to 22.2% of a Swiss university veterinary hospital (Sieber et al., 2010), and more recently for 19% in German equine clinics (Cuny et al., 2016). Furthermore, transmission of MRSA from veterinarians to their family members was also observed (Cuny et al., 2009; Walter et al., 2016). The use of wholegenome maps for studying LA-MRSA CC398 colonization in families of veterinarians indicated possible transmission of LAMRSA between humans (Bosch et al., 2015). There are only a few data on persistence of MRSA in horses after discharge from veterinary hospitals and on nasal colonization of humans who are in regular direct contact with them so far. A study in Belgium revealed low prevalence in horses and their caretakers outside veterinary hospitals (Van den Eede et al., 2013). Although nasal MRSA colonization of veterinarians and veterinary personnel is frequent in horse clinics, infections among this group of persons is infrequently documented. We have, however, to take into consideration that there are only notification systems for MRSA bacteremia cases in some countries but not for other cases. It seems likely that MRSA attributed to CC8 had initially introduced from a human hospital into an equine clinic followed by a long lasting intra and inter veterinary hospital dissemination. It remains to be shown whether it lost virulence for humans when adapting to horses. On the other hand demonstration of the IEC in the horse clinic subpopulation of CC398 requires alertness. Furthermore, the emergence of epidemic HA-MRSA MRSA ST22 and ST225 in equine clinics underlines the importance of surveillance for early identification of potentially epidemic clones and targeted transmission control measures at the interface between humans, livestock and companion animals (Fig. 1). Conflict of interests There are no conflicts of interests with respect to funding of own studies by pharmaceutical industry and other private enterprises. The same applies to royalties for lectures and manuscripts. Funding Own contributions to the topic reviewed here were supported by the German Ministry for Research and Education, grant No. 01KI1301 G (project cluster MedVetStaph). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. References Abdelbary, M.M., Wittenberg, A., Cuny, C., Layer, F., Kurt, K., Wieler, L.H., Walther, B., Skov, R., Larsen, J., Hasman, H., Fitzgerald, J.R., Smith, T.C., Wagenaar, J.A., Pantosti, A., Hallin, M., Struelens, M.J., Edwards, G., Böse, R., Nübel, U., Witte, W., 2014. Phylogenetic analysis of Staphylococcus aureus CC398 reveals a sublineage epidemiologically associated with infections in horses. PLoS One 9, e88083. Alba, P., Feltrin, F., Cordaro, G., Porrero, M.C., Kraushaar, B., Argudín, M.A., Nykäsenoja, S., Monaco, M., Stegger, M., Aarestrup, F.M., Butaye, P., Franco, A., Battisti, A., 2015. Livestock-associated methicillin resistant and methicillin susceptible Staphylococcus aureus sequence type (CC) 1 in european farmed animals: high genetic relatedness of isolates from italian cattle herds and humans. PLoS One 10 (8), e0137143. Anderson, M., Lefebvre, S., Rankin, S., Aceto, H., Morley, P., Caron, J., Welsh, R., Holbrook, T., Moore, B., Taylor, D., Weese, J., 2009. Retrospective multicenter study of methicillin-resistant Staphylococcus aureus infections in 115 horses. Equine Vet. J. 41, 401–405. Argudín, M.A., Tenhagen, B.A., Fetsch, A., Sachsenröder, J., Käsbohrer, A., Schroeter, A., Hammerl, J.A., Hertwig, S., Helmuth, R., Bräunig, J., Mendoza, M.C., Appel, B., Rodicio, M.R., Guerra, B., 2011. Virulence and resistance determinants of German Staphylococcus aureus ST398 isolates from nonhuman sources. Appl. Environ. Microbiol. 77, 3052–3060.

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