Staphylococcus aureus continues to evolve: MRSA without mec edition

I just returned from a wonderful MRSA conference this past week where I enjoyed learning about how European countries are handling antimicrobial use in livestock and the emergence of potential human pathogens like livestock-associated MRSA. Perhaps I will post further thoughts on the conference later in the week.  However, I just saw this new report in JAC on a novel resistance mechanism in S. aureus, so first things first.

It is known that hyper beta-lactamase producing strains of S. aureus exist and that some strains have chromosomal mutations and resultant modified penicillin binding proteins. These strains can have phenotypic methicillin resistance while lacking the mecA (or mec C) gene. Thus, they can evade detection by genotypic methods and the underlying mechanisms can be missed by phenotypic methods, as Dan nicely described here.

There is now a report by Xiaoliang Ba and colleagues that describes four clinical S. aureus isolates that were found to be MRSA but lacked mec A or mec C. The strains were from clinical wound infections and deposited in the Scottish MRSA Reference Lab. They belonged to sequence types 1, 15 (two isolates) and 8. Three strains were resistant to oxacillin, cefoxitin and PCN by ETest and disc diffusion and the fourth isolate was at the oxacillin Etest breakpoint, while three were beta-lactamase producers. Whole genome sequencing confirmed that none contained a mec-like sequence and that beta-lactamase production was not mediating the resistance. Interestingly they found similar single amino acid substitutions across sequence types in PBP1, PBP2 and PBP3 suggesting independent evolution of the same trait (homoplasy).

The authors acknowledge that their targeted search of the genomes could have missed other possible mechanisms of resistance in these isolates. I would add that this was in four isolates out of an unreported denominator, so we don't know the magnitude of the clinical impact yet. What we can say is that our surveillance techniques had better keep up with S. aureus. Unfortunately, it seems to be just as good at evolving away from our prevention methods as it does our antibiotics.

Obligatory S. aureus image courtesy of wikipedia

Addendum: For further insight, scroll down to read Dan's comment on this study


  1. Wondering what you guys think of this recent publication on the reasons why Northern Europe and the US diverged, and have stayed divergent, on MRSA rates.!

    1. Post going up tomorrow. Sneak peak is that it is an unbalanced and rather unprofessional attempt at supporting legislative mandates over scientific evidence that made almost no sense.

  2. Great post, Eli, and another good reminder of the challenges inherent in molecular diagnostics for antimicrobial resistance detection, and of the fact that our "old-fashioned" phenotypic tests aren't going anywhere anytime soon. The oxacillin MIC distribution of S. aureus is extremely bimodal, with most mecA negative strains having MICs of <=1, and most mecA positive strains having MICs of >=8. For example, in our most recent S. aureus surveillance study <2% of the 4100 clinical isolates we gathered had oxacillin MICs at 4. All four of the isolates in this paper had MICs of 2-4, right on the breakpoint (which for S. aureus and S. lugdunensis is <=2 for susceptible, >=4 for resistant). An emergent resistance mechanism is most likely to be detected initially using phenotypic tests (waiting for clinical failures to is waiting way too long, detecting a small attributable fraction of increased mortality related to resistance as opposed to other host or disease factors is almost impossible), but in an era of shrinking lab resources and reliance on automated susceptibility testing systems (many of which use algorithms that are based upon existing understanding of resistance mechanisms) it is likely that clinical labs will miss most newly emerging resistances initially (as we saw when automated systems were tested against the first few VRSAs and KPCs). One of the interesting tidbits from this paper is the consistently high ceftriaxone MIC for these four strains--I think I'll go through our banks to look for isolates with oxacillin MICs of 2-4 and ceftriaxone MICs > 32.......test them for beta-lactamase production (which is always the default mechanism we assume when we see elevated oxacillin MICs in mecA negative strains), and select some for further characterization.


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