Roles of Lytic Transglycosylases in Biofilm Formation and β-Lactam Resistance in Methicillin-Resistant Staphylococcus aureus
Roles of Lytic Transglycosylases in Biofilm Formation and β-Lactam Resistance in Methicillin-Resistant Staphylococcus aureus
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DOI：
10.1128/aac.01277-19
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发表时间：
2019-12-01
影响因子：
4.9
通讯作者：
Okuda, Ken-ichi
中科院分区：
文献类型：
--
作者：
Lopes, Anne-Aurelie;Yoshii, Yutaka;Okuda, Ken-ichi
金黄色葡萄球菌是许多社区暴发的原因，也是医院感染的最常见原因之一，具有很高的发病率和死亡率。虽然已经确定了几种细菌的裂解转糖基酶（LTs）在细胞分裂、生物膜形成和抗生素耐药性方面的功能，但它们在金黄色葡萄球菌中的作用在很大程度上仍然未知。已知的金黄色葡萄球菌LTs是免疫显性葡萄球菌抗原A （IsaA）和表皮葡萄球菌D蛋白（SceD）。我们的研究表明，在耐甲氧西林金黄色葡萄球菌（MRSA）菌株中，IsaA和SceD对生物膜形成和β -内酰胺耐药性的贡献不同。isaA缺失导致生物膜形成减少，而sceD不存在。此外，与野生型菌株相比，缺失isaa的菌株对β -内酰胺的抗性显著降低。在iaa缺失的菌株中，质粒表达mecA （MRSA中β -内酰胺抗性的主要决定因素）并没有恢复β -内酰胺抗性，这表明无论PBP2a的产生水平如何，isaA突变体都表现出β -内酰胺敏感性表型。总之，我们的结果表明IsaA是MRSA感染的潜在治疗靶点。
Staphylococcus aureus is responsible for numerous community outbreaks and is one of the most frequent causes of nosocomial infections with significant morbidity and mortality. While the function of lytic transglycosylases (LTs) in relation to cell division, biofilm formation, and antibiotic resistance has been determined for several bacteria, their role in S. aureus remains largely unknown. The only known LTs in S. aureus are immunodominant staphylococcal antigen A (IsaA) and Staphylococcus epidermidis D protein (SceD). Our study demonstrates that, in strains of methicillin-resistant S. aureus (MRSA), IsaA and SceD contribute differently to biofilm formation and beta-lactam resistance. Deletion of isaA, but not sceD, led to decreased biofilm formation. Additionally, in isaA-deleted strains, beta-lactam resistance was significantly decreased compared with that of wild-type strains. Plasmid-based expression of mecA, a major determinant of beta-lactam resistance in MRSA, in an isaA-deleted strain did not restore beta-lactam resistance, demonstrating that the beta-lactam susceptibility phenotype is exhibited by the isaA mutant regardless of the production level of PBP2a. Overall, our results suggest that IsaA is a potential therapeutic target for MRSA infections.