'Stealth MRSA' is hiding in its genes to develop antibiotic resistance, study reveals

Reviewed by James Ives, M.Psych. (Editor)Aug 7 2019

The superbug methicillin-resistant Staphylococcus aureus (MRSA) is a problem pathogen of long-standing clinical concern due to its resistance to methicillin and related antibiotics, such as oxacillin. MRSA variants termed oxacillin susceptible methicillin-resistant staphylococcus aureus (OS-MRSA) are a perplexing problem globally because of the diagnostic dilemma they represent. But a recent study of the organism by Creighton University's School of Medicine has identified a way to detect what an important gene "Stealth MRSA" is hiding within – its ability to become fully methicillin/oxacillin resistant in one simple step.

OS-MRSA has created confusion in clinical laboratories for the past decade because of the conflicting results it presents with different diagnostic testing methods. In a traditional disk susceptibility test, which takes days, the organism shows weakness to oxacillin. A separate molecular test, which takes hours, detects the presence of the mecA resistance gene in the organism, which suggests that it would be resistant to the antibiotic. The sum of the results presents bacterial identity crisis. Solving it is critical to successful treatment.

According to a research paper titled "Emergence of resistance in oxacillin-susceptible MRSA due to mecA sequence instability" published by the American Society for Microbiology Journals, the study identified changes in the DNA sequence of the mecA gene in seven OS-MRSA-infected samples from six different U.S. states through the process of whole genome sequencing. Results demonstrated that the cell makes errors in duplicating its DNA as it grows, which prevents the mecA gene from being expressed properly. But these duplication errors are easily correctable through a simple mutation when the cell is introduced to the antibiotic. This mutation activates the mecA gene, which leads to antibiotic resistance in the organism.

In OS-MRSA the mecA gene isn't expressed and is hiding, but it is one simple DNA base change away from reverting to full-blown resistance, which is why we called them Stealth MRSA. Our study suggests that follow-up susceptibility testing is warranted to reveal the stealth nature of these organisms. Without that, the results can be misreported as oxacillin susceptible when they should be reported as resistant MRSA."

Richard V. Goering, PhD, professor, Creighton University's School of Medicine

Goering, the author of the research paper, said another key finding in disk susceptibility testing was that resistance to oxacillin developed in the organisms during low levels of antibiotic exposure. When the concentration of antibiotics is not strong enough for treatment, an environment is created for the bacteria to mutate and grow, Goering said.

"That's why there is increasing concern about the overuse of antibiotics which can result in low antibiotic levels in the environment, allowing these organisms to grow and make the simplest of mutations to become fully resistant," Goering said.

Problem bacterial pathogens are of particular interest to Creighton University's Department of Medical Microbiology and Immunology because of the acute nature of the concern they present to the clinical community worldwide.

"Pharmaceutical companies have scaled back on the number of drugs that they are investigating, and major problem pathogens sooner or later begin to develop resistance to drugs that are used in therapy," Goering said. "MRSA is one of the most well-known problem organisms worldwide and accurate diagnosis is a critical key to effective therapy."