Methamphetamine Alters the Antimicrobial Efficacy of Phagocytic Cells during Methicillin-Resistant Staphylococcus aureus Skin Infection

Abstract

ABSTRACT Methamphetamine (METH) is a major drug of abuse in the United States and worldwide. Furthermore, Staphylococcus aureus infections and METH use are coemerging public health problems. S. aureus is the single most important bacterial pathogen in infections among injection drug users, with skin and soft tissue infections (SSTI) being extremely common. Notably, the incidence of SSTI, especially in drug users, is difficult to estimate because such infections are often self-treated. Although there is substantial information on the behavioral and cognitive defects caused by METH in drug users, there is a dearth of knowledge regarding its impact on bacterial infections and immunity. Therefore, we hypothesized that METH exacerbates S. aureus skin infection. Using a murine model of METH administration and wound infection, we demonstrated that METH reduces wound healing and facilitates host-mediated collagen degradation by increased expression and production of matrix metalloproteinase-2 (MMP-2). Additionally, we found that METH induces S. aureus biofilm formation and leads to detrimental effects on the functions of human and murine phagocytic cells, enhancing susceptibility to S. aureus infection. Our findings provide empirical evidence of the adverse impact of METH use on the antimicrobial efficacy of the cells that comprise innate immunity, the initial host response to combat microbial infection. IMPORTANCE METH is an extremely addictive central nervous system stimulant that is frequently administered by injection. SSTI, common problems among injection drug users, result in serious morbidity for patients and costly hospitalizations for treatment of superficial wounds and incision and drainage of abscesses; however, there has been little etiologic or preventive epidemiological research on this problem. In addition, the evasive nature of injection drug users toward medical care complicates our ability to accurately predict the prevalence of these infections. Hence, this study investigated the impact of METH use on S. aureus skin infection. Our findings demonstrate that this drug of abuse promotes biofilm formation and negatively impacts the wound healing process and innate immune function, exacerbating susceptibility to S. aureus infection. The findings may translate into new knowledge and development of therapeutic and public health strategies to deal with the devastating complications of METH abuse.