Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, PO Box 30001, 9700 RB Groningen, the Netherlands.
FEMS Microbiol Rev. 2022 Oct 28;46(5). doi: 10.1093/femsre/fuac025.
Staphylococcus aureus is an important human and livestock pathogen that is well-protected against environmental insults by a thick cell wall. Accordingly, the wall is a major target of present-day antimicrobial therapy. Unfortunately, S. aureus has mastered the art of antimicrobial resistance, as underscored by the global spread of methicillin-resistant S. aureus (MRSA). The major cell wall component is peptidoglycan. Importantly, the peptidoglycan network is not only vital for cell wall function, but it also represents a bacterial Achilles' heel. In particular, this network is continuously opened by no less than 18 different peptidoglycan hydrolases (PGHs) encoded by the S. aureus core genome, which facilitate bacterial growth and division. This focuses attention on the specific functions executed by these enzymes, their subcellular localization, their control at the transcriptional and post-transcriptional levels, their contributions to staphylococcal virulence and their overall importance in bacterial homeostasis. As highlighted in the present review, our understanding of the different aspects of PGH function in S. aureus has been substantially increased over recent years. This is important because it opens up new possibilities to exploit PGHs as innovative targets for next-generation antimicrobials, passive or active immunization strategies, or even to engineer them into effective antimicrobial agents.
金黄色葡萄球菌是一种重要的人兽病原体，其厚厚的细胞壁使其能够很好地抵御环境的侵害。因此，细胞壁是当今抗菌治疗的主要目标。不幸的是，金黄色葡萄球菌已经掌握了抗菌耐药性的艺术，这突出体现在耐甲氧西林金黄色葡萄球菌（MRSA）的全球传播上。细胞壁的主要成分是肽聚糖。重要的是，肽聚糖网络不仅对细胞壁功能至关重要，而且是细菌的致命弱点。特别是，这个网络不断地被至少 18 种不同的由金黄色葡萄球菌核心基因组编码的肽聚糖水解酶（PGHs）打开，这些酶促进了细菌的生长和分裂。这就把注意力集中在了这些酶的特定功能、它们的亚细胞定位、它们在转录和转录后水平的控制、它们对金黄色葡萄球菌毒力的贡献以及它们在细菌内稳态中的整体重要性上。正如本综述所强调的，近年来，我们对 PGH 在金黄色葡萄球菌中的不同功能方面的理解有了很大的提高。这一点很重要，因为它为利用 PGH 作为下一代抗菌药物、被动或主动免疫策略的创新靶点，甚至将其设计成有效的抗菌药物提供了新的可能性。
