Plasmid-Encoded Transferable mecB-Mediated Methicillin Resistance in Staphylococcus aureus

Karsten Becker; Sarah van Alen; Evgeny A. Idelevich; Nina Schleimer; Jochen Seggewiß; Alexander Mellmann; Ursula Kaspar; Georg Peters

Disclosures

Emerging Infectious Diseases. 2018;24(2):242-248. 

In This Article

Abstract and Introduction

Abstract

During cefoxitin-based nasal screening, phenotypically categorized methicillin-resistant Staphylococcus aureus (MRSA) was isolated and tested negative for the presence of the mecA and mecC genes as well as for the SCCmec-orfX junction region. The isolate was found to carry a mecB gene previously described for Macrococcus caseolyticus but not for staphylococcal species. The gene is flanked by β-lactam regulatory genes similar to mecR, mecI, and blaZ and is part of an 84.6-kb multidrug-resistance plasmid that harbors genes encoding additional resistances to aminoglycosides (aacA-aphD, aphA, and aadK) as well as macrolides (ermB) and tetracyclines (tetS). This further plasmidborne β-lactam resistance mechanism harbors the putative risk of acceleration or reacceleration of MRSA spread, resulting in broad ineffectiveness of β-lactams as a main therapeutic application against staphylococcal infections.

Introduction

Staphylococcal cassette chromosome mec (SCCmec)–mediated β-lactam resistance resulting from production of an additional penicillin-binding protein (PBP) 2a drastically limits the treatment options in cases of hospital- and community-related infections by staphylococci, leading to increased illness, death, and socioeconomic costs.[1,2] Besides methicillin-resistant coagulase-negative staphylococci, notorious for foreign body–associated infections, methicillin-resistant Staphylococcus aureus (MRSA) strains are a global public health priority, despite some countries in Europe reporting stabilizing or decreasing MRSA rates.[3–5] Since the initial reports of MRSA in 1961, several epidemic waves have resulted in threats of healthcare-, community-, and livestock-associated MRSA.[6–9]

For staphylococci, 2 PBP 2a-encoding genes, mecA and mecC, including several allotypes, have been described as chromosomally located genetic bases for phenotypic methicillin resistance.[10–14] In contrast, mecB, originally described as mecAm , was reported as part of a probable primordial form of a methicillin resistance gene complex often found in a transposon mec complex (Tn6045) in Macrococcus caseolyticus, a colonizer of animal skin.[15,16] Just recently, a mecD gene, most closely related to mecB, has been detected in bovine and canine M. caseolyticus isolates.[17]

The impact of plasmidborne resistance for staphylococci is abundantly demonstrated for β-lactamase–mediated penicillin resistance. Resistance rates are >60% in human S. aureus isolates from the general population and >90% from hospital-related cases, regardless of the clinical background.[18,19] In contrast to frequent interstrain and interspecies transmission of resistance plasmids by conjugation or transduction, only a relatively low rate of spontaneous horizontal transfer of SCCmec elements is assumed, resulting in still-manageable and controllable MRSA rates if prevention measures are adequate.[20–24] However, transferable methicillin resistance might bear the consequence of an almost complete loss of β-lactam drugs as the most efficient class of antibacterial drugs for treatment of staphylococcal infections. Here, we report both a plasmid-encoded, and thereby transferable, methicillin resistance encoded by mecB and the occurrence of this gene in an isolate of the genus Staphylococcus.

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