MRSA and Staphylococcus Aureus: Current Research Findings

Introduction to Staphylococcus Aureus Research

Much of the current research on Staphylococcus aureus centers on the emergence of antibiotic-resistant strains. In particular, the resistant strain MRSA is resistant to methicillin and related drugs. This has created a number of challenges for medical practitioners, as staph infections are among the more common infections that occur in healthcare settings. Researchers are approaching the problem from multiple angles: studying how infections spread within hospitals, investigating the genetic mechanisms behind resistance, and exploring alternative treatments for strains that no longer respond to standard antibiotics.

Intrahospital Transmission and Whole-Genome Sequencing

One thread of research concerns the spread of staph infection in the hospital setting. It has long been believed that S. aureus infections were transmitted between patients, and where outbreaks have occurred, the response has generally reflected this view — patients have been segregated and similar containment measures applied. Recent research has shown, however, that transmission between patients in the intrahospital setting does not occur nearly as frequently as previously thought (Long, Beres, Olsen & Musser, 2014). This is an important finding for healthcare facilities because it changes the way staph outbreaks are understood, and consequently the way they are managed.

There are a number of different strains of Staphylococcus that can exist in a hospital setting, given that staph is a heterogeneous organism. S. aureus is fairly well established in many hospitals, making the risk of infection correspondingly high. The researchers tested the genomes of S. aureus collected from four Houston-area hospitals over a period of six months. Their findings indicated that the strains found in different patients were not the same organism passed from one individual to another, but were independently acquired. Where a staph infection occurs, it may therefore have more to do with the overall cleanliness of the facility than with patient-to-patient contact.

The findings lead the authors to conclude that there is a fundamental difference between everyday staph infections and outbreak scenarios. Importantly, the results suggest that much of the testing on which current knowledge is based is not refined enough to detect subtle differences between staph strains. The ability to identify distinct strains through whole-genome sequencing enabled the authors to determine that infections were not usually transmitted between patients but were instead independently acquired. This has significant consequences for how hospitals approach infection control.

Genetic Mutations and Chronic Staph Infections

A second thread of research concerns chronic staph infections. Kriegeskorte et al. (2014) investigated this issue at the genetic level. They studied thymidine-dependent small-colony variants of Staphylococcus aureus and found that these variants contained mutations in ThyA. These mutations led to inactivity of thymidylate synthase proteins, which in turn produced increased S. aureus virulence; genes responsible for colonization were upregulated as a result. The consequence is that these particular strains colonize more easily and with greater virulence — a mechanism that explains the chronic staph infections observed in the study.

The findings are significant because these virulent small-colony variants are common in patients receiving long-term treatment with trimethoprim-sulfamethoxazole (TMP-SMX), an antibiotic widely used to treat a range of infections. The findings also suggest — though do not conclusively prove — that the mutations arise from heavy, prolonged use of this antibiotic. The strain appears to adapt so that long-term antibiotic exposure results in a mutation toward a more virulent form, which then drives the chronic S. aureus infection. There are implications both for treating such chronic infections and for determining the best initial course of action — one that manages the underlying infection without encouraging the development of these mutations in the first place.

References

Haba, E., Bouhdid, S., Solana, N., Marques, A., Espuny, M., Celma, M., & Manresa, A. (2014). Rhamnolipids as emulsifying agents for essential oil formulations: Antimicrobial effect against Candida albicans and methicillin-resistant Staphylococcus aureus. International Journal of Pharmaceutics, 476, 134–141.

Kriegeskorte, A., Block, D., Drescher, M., Windmuller, N., Mellmann, A., Baum, C., Neumann, C., Lore, N., Bragonzi, A., Liebau, E., Hertel, P., Seggeweiss, J., Becker, K., Proctor, R., Peters, G., & Kahl, B. (2014). Inactivation of thyA in Staphylococcus aureus attenuates virulence and has a strong impact on metabolism and virulence gene expression. mBio, 5(4), 1–15.

Long, S., Beres, S., Olsen, R., & Musser, J. (2014). Absence of patient-to-patient intrahospital transmission of Staphylococcus aureus as determined by whole-genome sequencing. mBio, 5(5), 1–10.