Methicillin-resistant Staphylococcus aureus: livestock-associated, antimicrobial, and heavy metal resistance Cwengile C Dweba,1 Oliver T Zishiri,1 Mohamed E El Zowalaty2 1Discipline of Genetics, School of Life Sciences, College of Agriculture Engineering and Sciences, University of KwaZulu-Natal, Durban, South Africa; 2Microbiology and Virology Research Group, School of Health Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa Abstract: Staphylococcus aureus is an opportunistic pathogen of human and other mammals that is of increasing clinical and veterinary importance due to its ability to rapidly develop antimicrobial resistance. The injudicious use of antibiotics has given rise to the emergence of antibiotic resistant S. aureus strains, most importantly methicillin-resistant Staphylococcus aureus (MRSA). The emergence of livestock-associated MRSA (LA-MRSA) has highlighted the importance of directed research toward its prevention, as well as the need for the discovery and development of more efficient treatment than is currently available. Furthermore, the treatment of MRSA is complicated by the co-selection of heavy metal and antibiotic resistance genes by microorganisms. Livestock and livestock production systems are large reservoirs of heavy metals due to their use in feed as well as environmental contaminant, which has allowed for the selection of LA-MRSA isolates with heavy metal resistance. The World Health Organization reported that Africa has the largest gaps in data on the prevalence of antimicrobial resistance, with no reports on rates for LA-MRSA harboring heavy metal resistance in South Africa. This review aimed to report the emergence of LA-MRSA in South Africa, specifically the most frequent sequence type ST398, globally. Furthermore, we aimed to highlight the importance of LA-MRSA in clinical and food security, as well as this research gap in South Africa. This review sheds light on the prevalence of heavy metals in livestock farms and abattoirs, and focuses on the phenomenon of the co-selection of heavy metal and antibiotic resistance genes in MRSA, emphasizing the importance of a focused direction for research in humans, animals as well as environment using one-health approach. Keywords: Staphylococcus aureus, methicillin resistance, livestock, MRSA, humans, antimicrobial resistance, antibiotics, resistance, virulence, heavy metals, LA-MRSA, one health