Zinc resistance of Staphylococcus aureus of animal origin is strongly associated with methicillin resistance

Abstract

Please cite this article as: Cavaco, L.M., Hasman, H., Aarestrup, F.M., on behalf of the MRSA collaborating group (MRSA-CG), Zinc resistance of Staphylococcus aureus of animal origin is strongly associated with methicillin resistance, Veterinary Microbiology (2010Microbiology ( ), doi:10.1016Microbiology ( /j.vetmic.2011 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The test population consisted of 476 porcine MRSA isolates from ten European 30 countries, 18 porcine MRSA isolates from Canada and seven MRSA from China, 92 31 MRSA and 60 methicillin-susceptible S. aureus (MSSA) isolates from veal calves in the 32Netherlands and 88 porcine MSSA isolates from four European countries. Most porcine 33 MRSA (n=454) and all bovine MRSA belonged to clonal complex (CC) 398 whereas 37 34 of the pig MRSA from Europe and the seven Chinese isolates belonged to other CCs 35 and 3 isolates were not classified into a CC. 36All isolates were tested for susceptibility to zinc chloride and copper sulphate using 37 agar dilution and tested by PCR for the czrC gene encoding zinc resistance. 38Phenotypic zinc resistance (MIC>2mM) was observed in 74% (n=324) and 42% (n=39) 39 of European MRSA CC398 from pigs and veal calves respectively, and in 44% of the 40 Canadian isolates (n=8), but not among the Chinese isolates. Almost all (99%) zinc-41 resistant MRSA carried czrC. Of the 37 European non-CC398 MRSA, 62% were 42 resistant to zinc, but only 46% of them carried czrC,. The MICs of the MSSA isolates to 43 zinc chloride ranged from 1 to 4 mM and none carried czrC. The MICs of copper 44 sulphate were neither associated with methicillin resistance nor with the detection of 45 czrC. 46This study showed that zinc resistance and the czrC gene is widespread among 47 CC398 MRSA isolates. This suggests that the use of zinc in feed might have 48 contributed to the emergence of MRSA. 49 50

Resistance to Zinc and Cadmium inStaphylococcus aureusof Human and Animal Origin

“…Previous studies observed all tested MSSA isolates of human and swine origin to be susceptible to zinc and cadmium. 11,21 However, our study observed genotypic zinc and cadmium resistance in 6.6% of MSSA isolates, suggesting a potential reservoir for this resistance in MSSA. The odds of zinc and cadmium resistance were observed to be 48% lower in study-defined LA-SA strains isolated from human samples.…”

“…Our study observed 19.6% of MRSA isolates to be czrC positive compared to other studies from Europe that observed prevalence of 74% (MRSA from swine farms), 11 58% (human and swine MRSA), 17 70% (swine MRSA), and 4 1 % (veal MRSA). 21 The relatively low prevalence could be due to exclusion of S. aureus isolates that were MRSA by presence of the mecA gene but lacked antibiotic susceptibility NOTES. Antimicrobial susceptibility was tested by broth microdilution method.…”

“…This finding is consistent with results observed in European studies, further strengthening the evidence of the czrC gene on the SCCmec element. 17,21 A recent study on antimicrobial resistance classified MRSA as MDR due to coresistance to other /3-lactams and cephalosporins. 36 This explains the association of S. aureus zinc and cadmium resistance with MDR observed in our study.…”

“…32 Identification of spa type for each isolate and spa cluster complexes using BURP was performed using Ridom StaphType (ver 2.2.1; Ridom). 28,33 All isolates were tested for methicillin resistance (mecA gene), 34 staphylococcal complement inhibitor (sen gene), 31 and zinc-cadmium resistance {czrC gene), 17,21 as per previously published standard polymerase chain reaction (PCR) protocols. Positive and negative controls were used in all molecular assays.…”

Livestock-Associated MRSA and Its Current Evolution

“…To date, little variation has been seen in the prevalence of CC398 strains; however, with increased use of zinc oxide in some European countries, SCCmec type V (5C2&5) may increase. Indeed, after the discovery of the zinc oxide resistance gene (czrC) in MRSA CC398 [118] and its location on SCCmec type V [119][120][121], a randomized controlled trial and an epidemiologic study showed that zinc oxide selects for MRSA CC398 SCCmec type V in vivo [122,124]. The possible coselection of MRSA through zinc oxide application in pigs is supported further by pig experiments showing that treatment with zinc oxide alone and in combination with tetracycline influences the MRSA load in the nasal cavity [124].…”