Genomic Basis of Occurrence of Cryptic Resistance among Oxacillin- and Cefoxitin-Susceptible mecA-Positive Staphylococcus aureus.
Genomic Basis of Occurrence of Cryptic Resistance among Oxacillin- and Cefoxitin-Susceptible mecA-Positive Staphylococcus aureus.
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DOI：
10.1128/spectrum.00291-22
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发表时间：
2022-06-29
影响因子：
3.7
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中科院分区：
文献类型：
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苯唑西林和头孢西丁敏感的mecA阳性金黄色葡萄球菌是一种新的“隐形”耐甲氧西林的S。金黄色葡萄球菌（MRSA）型。在这里，我们对两株苯唑西林和头孢西丁敏感的mecA阳性MRSA分离株的全基因组进行测序，这些MRSA分离株来自广州一名哺乳期妇女的乳房脓肿和一名健康学生的鼻拭子，以调查其发生的机制。通过暴露于亚MIC的头孢西丁（含或不含莫匹罗星）来选择这些分离株的回复。测定亲本菌株及其回复突变体的mecA表达，并对回复突变体的全基因组进行测序。对两种菌株进行的比较全基因组分析显示，临床菌株的mecA通过在基因串联重复区的第262位插入单bp而突变，并且该突变导致形成提前终止密码子。通过在mecA的第二启动子区（~ 35 bp）中的新的G-至-A碱基取代来突变定殖菌株。突变株697的mecA表达量是亲本菌株的37倍。尽管亲本菌株199的mecA表达水平甚至高于其回复突变体，但其cDNA序列含有单bp插入。总的来说，mecA的第二启动子的错义突变和单取代突变都可以使MRSA分离株成为“隐形”MRSA，从而强调了将表型检测与mecA或青霉素结合蛋白2a检测相结合以鉴定MRSA的重要性。苯唑西林和头孢西丁敏感的mecA阳性金黄色葡萄球菌是一种新型的“隐形”耐甲氧西林的金黄色葡萄球菌。金黄色葡萄球菌（MRSA），其难以使用常规方法检测。为了研究其发生的基因组基础，我们对来自广州一名哺乳期妇女乳房脓肿和一名健康学生鼻拭子的两株先前回收的苯唑西林和头孢西丁敏感的mecA阳性MRSA分离株进行了全基因组测序。除了临床分离株199中的mecA外，不存在完整的SCCmec结构。此外，在临床菌株中观察到一种新的单碱基对插入，导致提前终止和移码突变。定殖分离物697具有Scc-mec-型IVa，并且mecA的第二启动子区（~ 35 bp）通过新的G-至-A碱基取代而突变。苯唑西林和头孢西丁敏感的mecA阳性S.通过暴露于亚最小抑制性头孢西丁（有或没有莫匹罗星）来选择金黄色葡萄球菌对耐药MRSA分离株的耐受性。
The oxacillin– and cefoxitin-susceptible mecA–positive Staphylococcus aureus is a novel “stealth” methicillin-resistant S. aureus (MRSA) type. Here, we sequenced the whole genome of two oxacillin- and cefoxitin-susceptible mecA-positive MRSA isolates from breast abscesses in a lactating woman and a nasal swab of a healthy student in Guangzhou for investigating the mechanism underlying its occurrence. The reversion of these isolates was selected by exposure to sub-MICs of cefoxitin with or without mupirocin. The mecA expression of both parental strains and their revertants was determined, and the whole genome of the revertants was sequenced. Comparative whole-genome analyses performed for both strains revealed that mecA of the clinical strain was mutated by a single-bp insertion at the 262nd position in the tandem repeat region of the gene, and this mutation that led to the formation of a premature stop codon. The colonizing strain was mutated by a novel G-to-A base substitution in the second promoter region (–35 bp) of mecA. The mecA expression level of strain 697 revertant was 37 times higher than that of the parental strain. Although the mecA expression level was even higher for parental strain 199 compared with that for its revertant, its cDNA sequence contained a single-bp insertion. Collectively, both the missense and single substitution mutations of the second promoter of mecA could render MRSA isolates as “stealth” MRSA, thereby emphasizing the importance of combining phenotype tests with mecA or penicillin-binding protein 2a detection for the identification of MRSA. IMPORTANCE The oxacillin- and cefoxitin-susceptible mecA-positive Staphylococcus aureus is a novel type of “stealth” methicillin-resistant S. aureus (MRSA), which is difficult to be detected using conventional methods. To investigate the genomic basis of their occurrence, we sequenced the whole genome of two previously recovered oxacillin- and cefoxitin-susceptible mecA-positive MRSA isolates from breast abscesses in a lactating woman and a nasal swab of a healthy student in Guangzhou. Complete SCCmec structure was absent except for mecA in clinical isolate 199. Additionally, a novel single-base pair insertion was observed in the clinical strain, which resulted in premature termination and a frameshift mutation. The colonizing isolate 697 had a Scc-mec-type IVa, and the second promoter region (–35 bp) of mecA was mutated by a novel G-to-A base substitution. The reversion of oxacillin- and cefoxitin-susceptible mecA-positive S. aureus to resistant MRSA isolates was selected by exposure to subminimum inhibitory cefoxitin with or without mupirocin.
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