Methicillin Resistant Staphylococcus Aureus in Livestock: Origins and Importance to Animal and Public Health

INTRODUCTION Penicillin and other β-lactam antimicrobials act by binding to a transpeptidase involved in cell wall peptidoglycan synthesis disrupting the bacterial cell wall resulting in death of the bacterium. One mechanism by which bacteria become resistant to β-lactam antimicrobials is through the production of enzymes such as β-lactamase that destroy the antimicrobial’s β-lactam ring rendering the drug ineffective. Shortly after the introduction of penicillin in the 1940s, this type of resistance became prevalent leading to the development of new synthetic β-lactam drugs such as methicillin that resisted β-lactamase. After only a few years of use, however, S. aureus became resistant to methicillin. 1 Resistance to methicillin is not mediated through production of β-lactamase, but rather methicillin resistant staphylococci have acquired a mobile genetic element known as staphylococcal cassette chromosome mec (SCCmec). This SCC carries a gene known as mecA which encodes for an altered penicillin-binding protein (PBP2a or PBP2’). The PBP2a has a lower affinity for β-lactam antimicrobials than the normal PBP such that these antimicrobials are ineffective. Importantly, the SCC containing the mecA gene can spread between bacteria within staphylococcal populations. Furthermore, the SCC contains additional insertional DNA sequences that allow for incorporation of additional antimicrobial resistance markers. These insertional sequences explain why many methicillin-resistant staphylococci are resistant to non-β-lactam antimicrobials that act through mechanisms other than interference with bacterial cell wall synthesis (e.g., macrolides, fluoroquinolones), and thus why methicillin-resistant strains can be multi-drug resistant. While methicillin resistance is often associated with Staphylococcus aureus, so-called MRSA, it can be commonly found in other non-S. aureus staphylococci most frequently classified as the coagulase-negative staphylococci (CNS), and there is speculation that MRSA may have acquired the mecA gene from CNS. The moniker methicillin-resistant stems from the original description of MRSA in 1961. 1 However, routine diagnostic screening now employs testing for in vitro susceptibility to either oxacillin or cefoxotin as methicillin is no longer used in clinical practice. In addition to phenotypic characterization using susceptibility testing, molecular methods (polymerase chain reaction; PCR) that detect the mecA gene are now employed to confirm a diagnosis of mecA mediated resistance as bacteria expressing β-lactamase may be falsely identified as mecA positive when using phenotypic methods alone (conventional antimicrobial susceptibility testing). While the PCR test for confirming a diagnosis has been widely employed, recently mecA gene variants have been identified in some staphylococcal isolates from people and dairy cattle that are not detected using the current PCR test. 2 Hence, these mecA variants may be misclassified as methicillin susceptible using the current PCR detection method. Therefore a combination of phenotypic (antimicrobial susceptibility testing) and genotypic (mecA PCR) identification methods is recommended. Methicillin-resistant staphylococcal strains are not necessarily more virulent than their methicillin susceptible counterparts, but are more difficult to treat as they are often resistant to multiple classes of antimicrobial drug as illustrated above. Historically, MRSA was associated with hospital-acquired (HA-MRSA) infections. More recently, however, there has been an increased incidence of non-healthcare-associated, or so-called community-acquired MRSA (CA-MRSA) infections. Additionally, starting in the early 2000s, a new type of MRSA began to emerge, the so-called livestock-associated MRSA (LA-MRSA). In both humans and animals, inapparent colonization is far more common than outright infection, and colonization is more often transient than chronic. However, colonization does increase the host’s risk of MRSA infection.