Park Sohee, Jeon Wook-Jong, Lee Yeseul, Lim Chae Lim, Lee Eunyeong, Oh Han Byeol, Lee Gyu Sung, Kwon Oh Hyun, Ryu Bumhan, Cho Yong-Joon, Kim Chung Sub, Yoon Sung-Il, Chung Jeong Min, Cho Hongbaek
Department of Biological Sciences, College of Natural Sciences, Sungkyunkwan University, Suwon 16419, Republic of Korea.
Department of Biotechnology, The Catholic University of Korea, Bucheon 14662, Republic of Korea.
Proc Natl Acad Sci U S A. 2025 Jan 28;122(4):e2418854122. doi: 10.1073/pnas.2418854122. Epub 2025 Jan 22.
Bacterial cell wall assembly and remodeling require activities of peptidoglycan (PG) hydrolases as well as PG synthases. In particular, the activity of DD-endopeptidases, which cleave the 4-3 peptide crosslinks in PG, is essential for PG expansion in gram-negative bacteria. Maintaining optimal levels of DD-endopeptidases is critical for expanding PG without compromising its integrity. In , the levels of major DD-endopeptidases, MepS and MepH, along with the lytic transglycosylase MltD, are controlled by the periplasmic protease Prc and its outer membrane adaptor NlpI. However, the mechanisms regulating the turnover of these PG hydrolases have remained unclear. In this study, we identified a periplasmic protein, BipP (formerly YhjJ), that negatively controls the NlpI-Prc system. Further analyses indicate that BipP exerts this control by interacting with NlpI and inhibiting its substrate recognition in response to low DD-endopeptidase activity, providing insight into the homeostatic control of PG hydrolysis and cell wall expansion.
细菌细胞壁的组装和重塑需要肽聚糖(PG)水解酶以及PG合酶的参与。特别是,能切割PG中4-3肽交联的DD-内肽酶的活性对于革兰氏阴性菌中PG的扩展至关重要。维持DD-内肽酶的最佳水平对于在不损害其完整性的情况下扩展PG至关重要。在大肠杆菌中,主要的DD-内肽酶MepS和MepH以及溶菌转糖基酶MltD的水平受周质蛋白酶Prc及其外膜衔接蛋白NlpI的控制。然而,调节这些PG水解酶周转的机制仍不清楚。在本研究中,我们鉴定了一种周质蛋白BipP(以前称为YhjJ),它对NlpI-Prc系统起负调控作用。进一步分析表明,BipP通过与NlpI相互作用并在低DD-内肽酶活性时抑制其底物识别来发挥这种调控作用,这为PG水解和细胞壁扩展的稳态控制提供了见解。