生牛乳中金黄色葡萄球菌异质性耐药及机制研究OA北大核心

This experiment was conducted to study the drug resistances of Staphylococcus aureus isolated from raw milk,the prevalence of heteroresistance of Staphylococcus aureus and explore the mechanism of heteroresistance.Thirty-six Staphylococcus aureus isolates were isolated from 179 batches of raw milk collected from Northeast,North China,East China,South China,Northwest and Southwest.The sensitivity and resistance of Staphylococcus aureus were identi-fied using broth microdilution method.The combination of disk diffusion method and E-test method was used to screen suspected heteroresistant strains from strains with sensitive pheno-types,and then the suspected heteroresistant strains were confirmed by Population analysis profi-ling(PAP).The stability of the heteroresistant phenotype after serial passage was measured.Fi-nally,whole-genome sequencing and whole genome re-sequencing analysis were used to deter-mine the heteroresistant mechanisms.The results showed that 36 strains of Staphylococcus au-reus were resistant to β-lactam antibiotics,the resistant rate to ranges from 11.11％ to 61.11％,and had high sensitivity to tetracycline and aminoglycoside antibiotics.19 combinations of Staph-ylococcus aureus and antibiotics with heteroresistant were identified through initial screening,and it was confirmed that the 3 combinations exhibited heteroresistant phenotypes,of which only amoxicillin-clavulanate-J23 heteroresistant stabled after serial passage.This study demonstrates that S.aureus of raw milk origin is high resistant to β-lactam and quinolone antimicrobials.Het-eroresistant mechanisms to amoxicillin-clavulanic acid are associated with blaZ and metal β-lacta-mase expression.Heteroresistant mechanisms to tetracyclines is associated with tetracycline ef-flux pumps and resistance proteins.