Investigation of antibiotic resistance genes in staphylococcal isolates from bovine milk

现代医学和兽医实践依赖于有效的抗生素来预防和治疗人类和动物的感染。细菌中抗生素耐药性的普遍存在是21世纪公共卫生中最棘手的挑战之一。大约80%的抗生素总消耗量用于食用动物。因此，更好地了解农场使用抗生素的影响将为公共政策提供更强大的平台。奶牛场使用抗生素最常见的原因是治疗和预防乳腺炎。乳腺炎是一种具有重大经济意义的疾病（加拿大乳制品行业每年损失约3.5亿美元）。乳腺炎可由革兰氏阳性和革兰氏阴性细菌引起。大多数治疗乳腺炎的抗菌药物都是针对革兰氏阳性细菌的。牛乳腺最常见的革兰氏阳性细菌是葡萄球菌，包括金黄色葡萄球菌和凝固酶阴性葡萄球菌（CNS）。大多数牛奶金黄色葡萄球菌和CNS分离株具有多重耐药性。葡萄球菌中一种特殊类型的抗菌素耐药性，即甲氧西林耐药性（MR），最近一直是乳腺炎研究人员关注的焦点，因为-内酰胺类抗生素是奶牛场最常用的药物。******我的长期研究目标是了解乳腺炎期间宿主-病原体的相互作用。在过去的几年里，我们一直在研究牛奶金黄色葡萄球菌和CNS分离株的抗生素耐药性。我未来5年的短期目标是：(1)揭示这些分离株的组织和结构特征，特别是抗生素耐药基因，并了解乳葡萄球菌分离株与来自其他动物和人类的已发表葡萄球菌菌株之间的系统发育关系；(2)确定调控rna（细菌称为小rna）是否以及如何调控抗生素耐药基因的表达；(3)研究金黄色葡萄球菌与中枢神经系统体外和体内抗生素耐药基因的水平基因转移。提出的实验具有原创性和创新性。新的和潜在的变革性发现有望预防或减少抗生素耐药性的转移。******这项拟议的研究将对乳腺炎的管理和治疗产生影响，包括根据耐药模式选择抗生素和制定新的治疗策略。通过减少乳腺炎的发生，这将对动物福利产生积极影响。此外，了解牛奶中金黄色葡萄球菌和CNS分离物的抗生素耐药基因与人类健康有关，因为来自牛奶的MRSA和MRCNS可能会对人类健康造成危害，无论是通过葡萄球菌物种之间的耐药性基因水平转移，还是通过耐药病原体在人与动物之间的直接传播。＊＊＊＊＊＊＊＊＊＊＊

Modern medical and veterinary practice relies on effective antibiotics to prevent and treat infections in humans and animals. The prevalence of antibiotic resistance in bacteria is one of the most intractable challenges in 21st century public health. Approximately 80% of the total antibiotic consumption are used in food animals. Thus, a better understanding of the impacts of antibiotics used on farms would produce a more robust platform for public policy. The most common reason for antibiotic use on dairy farms is to treat and prevent mastitis. Mastitis is a disease of major economic importance (approximately $350 million loss per year for the Canadian dairy industry). Mastitis can be caused by both Gram-positive and Gram-negative bacteria. Most antimicrobial therapies for mastitis have been targeted against Gram-positive bacteria. The most common Gram-positive bacteria from bovine mammary glands are staphylococci, including Staphylococcus aureus and coagulase-negative staphylococcus (CNS). Most milk S. aureus and CNS isolates are multi-drug resistant. A particular type of antimicrobial resistance among staphylococci, methicillin resistance (MR), has been a recent focus of mastitis researchers, since members of the -lactam class of antibiotics are the most commonly used drugs on dairy farms. ******My long-term research objective is to understand the host-pathogen interaction during mastitis. We have been working on antibiotic resistance of milk S. aureus and CNS isolates for the last several years. My short-term objectives for the next 5 years are (1) to reveal organizational and structural characteristics of these isolates, especially for antibiotic resistant genes and to understand the phylogenetic relationship between milk staphylococcal isolates and published staphylococcal strains from other animals and humans; (2) to determine whether and how regulatory RNAs (called small RNAs for bacteria) regulate expression of antibiotic resistant genes; (3) to study the horizontal gene transfer of antibiotic resistance genes in vitro and in vivo between S. aureus and CNS. The proposed experiments are original and innovative. Novel and potentially transformative findings are expected for preventing or reducing the transfer of antibiotic resistance. ******This proposed research will have an impact on management and treatment of mastitis, in terms of choice of antibiotics based on resistance patterns and development of new treatment strategies. By reducing occurrence of mastitis, it will have a positive impact on animal welfare. In addition, understanding antibiotic resistant genes in S. aureus and CNS isolates from milk is relevant to human health because MRSA and MRCNS from milk potentially pose a human health hazard, both through horizontal transfer of resistance genes between staphylococcal species and through direct transmission of resistant pathogens between humans and animals. ***********