Mitigation of antimicrobial resistance in staphylococcal isolates from bovine milk

点击翻译按钮获取中文摘要

One of today's biggest world health challenges is bacteria that are resistant to the antibiotics used to treat infections. Animal agriculture is the largest user of antibiotics in Canada to prevent and treat diseases. In the dairy industry, one major use of antibiotics is for treating mastitis, caused mainly by pathogenic bacteria. Among them, staphylococci, including Staphylococcus aureus (S. aureus) (major pathogens) and coagulase-negative staphylococcus (CNS) (minor pathogens) are important. Treatment of S. aureus mastitis has been complicated by its ability to persist in tissues and evade the host immune response and by lack of effective vaccines. In addition, unusually frequent acquisition of antimicrobial resistance among staphylococci, especially methicillin resistance, could contribute to significantly low cure rates. We have been working on antibiotic resistance of milk S. aureus and CNS isolates for the last 10 years. This proposed research builds on our continuing efforts and successes and takes advantage of our established collaboration with scientists in various countries. We will perform the following: (1) to identify unique methicillin-resistant determinants and other antimicrobial resistance (AMR) genes in S. aureus and CNS from mastitic milk. The results will contribute to the surveillance of AMR in animals and to reveal new targets for intervention; (2) to uncover specific genetic mutations during the development of tolerance after cyclic exposure to high concentrations of antibiotics. Resistance is a primary determinant in the survival of bacteria under antibiotics. However, bacteria can also become recalcitrant to antibiotic treatment, without developing resistance, a phenomenon termed "tolerance". By studying genetic changes during the development of tolerance, we can understand how new resistance is developed; and (3) to develop novel antimicrobial peptides (AMPs) and peptide nucleic acids (PNAs) for eliminating intracellular S. aureus in bovine mammary epithelial cells. Both AMPs and PNAs are novel alternatives to traditional antibiotics to tackle the problem of bacterial multidrug resistance. The proposed research is highly original and innovative for solving the AMR problem in mastitis-causing bacteria. This proposed research will contribute to understanding mechanisms for the formation of bacterial AMRs and to reduce mastitis in dairy cows. In addition, this research may be relevant to human health because methicillin-resistant S. aureus and CNS from milk potentially pose a hazard to human health, both through horizontal transfer of resistance genes between staphylococcal species and through direct transmission of resistant pathogens between humans and animals. Therefore, this proposed research has potential economic benefits to dairy producers, health benefits to animal welfare and possibly to humans, and social benefits to policy making for dealing with the AMR problem as well as training highly qualified personnel.