EAGER: The Role of Engineered Systems in Adaptation of Staphylococcus Aureus

Staphylococcus aureus (SA) adapts to selective pressures via mobile genetic elements (MGEs) that increase virulence and confer resistance. Increased prevalence of community acquired Methicillin Resistant SA (CA-MRSA) infections is a dominant cause of infectious disease morbidity and mortality in the USA. More deaths in 2005 were attributable to infections by SA than HIV/AIDS in the USA. CA-MRSA is endemic and emerging environmental reservoirs are suspected. Recent findings of MRSA in wastewaters suggests that our sewage collection and treatment systems may serve as reservoirs, transport, and adaptive hot-spots for CA-MRSA. I posit wastewater systems have conditions that facilitate horizontal gene transfer (HGT) of MGEs between SA strains and other bacteria. An example is the conjugative plasmid for vancomycin-resistant enterococci that has resulted in the emergence of vancomycin-resistant SA (VRSA). Another is the speG-mediated adaptations that enhance SA survival on skin obtained from S. epidermis. The project will investigate the prevalence, and select MGEs, of SA across two, wastewater treatment plants; one connected to multiple, hospitals and the other collecting primarily suburban sewage. Preliminary data from 10 pairs of influent samples at the plants has documented the prevalence of both SA and MRSA to be greater in the hospital fed system. This research will build upon these findings, but proposes expanding to investigate changes in select MGEs of SA that may occur as a result of treatment. It is hypothesized that the SA leaving the treatment plant systems will have more MGEs than those entering the systems, especially those relative to persistence and antibiotic resistance. It is posited that the processes of primary settling and activated sludge enhance transmission of plasmid-encoded vancomycin-resistance from enteric bacteria to SA. The acquisition of MGEs by SA in sewage treatment plants may enhance survival of these organisms so that they persist in environmental reservoirs downstream and create another potential route of transmission. This research seeks to apply recent advances in clinical and ecological research to understand the potential risks associated with engineered systems w/respects to evolving, pathogenic microbiota. To date, no studies have compared the prevalence of MRSA in hospital sewer systems to that of domestic sewage w/o hospital wastes. Only a couple of studies have looked at the prevalence of MRSA in hospital sewer systems and at the inlet of the sewage treatment plants receiving this waste, but their focus was on occupational safety issues, not adaptation. This study is the first step in assessing the potential for hospitals and sewage treatment systems to serve as an environmental reservoir of MGEs for SA. There have been no systematic studies that seek to link sewage treatment to the adaptation of SA. SA transmission is thought to require close contact with infected people, or contaminated fomites, even though survival for many months has been documented. Acquisition of MGEs results in adaptations that further enhance protective biofilm formation. If this research shows an increase in the prevalence and MGEs of SA from different sources, and across the treatment schemes, then a link between clinical and epidemiological findings (outbreaks of new SA strains with MGEs from enterococci and S. epidermis), recent molecular biology observations of microbial ecology (enteric MGEs isolated from activated sludge), and environmental engineering (new design and control systems) will be forged. The proposed research will expand our knowledge of how engineered systems create conditions conducive to evolution of more virulent and environmentally robust strains of non-enteric pathogens, spurring a rethinking of the primary purpose of sewage treatment and the control systems engineers put into place to protect health and the environment. Results may change the way we view and design sewage collection, treatment, and distribution systems, track adaptation of microbes, and prevent disease transmission. The research proposed lies along the intersections of several disciplines, a factor that tends to be associated with maximal impact.