Functional profiling of CHAP domain-containing peptidoglycan hydrolases of Staphylococcus aureus USA300 uncovers potential targets for anti-staphylococcal therapies
Min Wang , Xiaofang Li , Francis M. Cavallo , Harita Yedavally , Sjouke Piersma , Elisa J.M. Raineri , Elias Vera Murguia , Jeroen Kuipers , Zhenhua Zhang , Jan Maarten van Dijl , Girbe Buist
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引用次数: 0
Abstract
The bacterial pathogen Staphylococcus aureus employs a thick cell wall for protection against physical and chemical insults. This wall requires continuous maintenance to ensure strength and barrier integrity, but also to permit bacterial growth and division. The main cell wall component is peptidoglycan. Accordingly, the bacteria produce so-called peptidoglycan hydrolases (PGHs) that cleave glycan strands to facilitate growth, cell wall remodelling, separation of divided cells and release of exported proteins into the extracellular milieu. A special class of PGHs contains so-called ‘cysteine, histidine-dependent amidohydrolase/peptidase’ (CHAP) domains. In the present study, we profiled the roles of 11 CHAP PGHs encoded by the core genome of S. aureus USA300 LAC. Mutant strains lacking individual CHAP PGHs were analysed for growth, cell morphology, autolysis, and invasion and replication inside human lung epithelial cells. The results show that several investigated CHAP PGHs contribute to different extents to extracellular and intracellular growth and replication of S. aureus, septation of dividing cells, daughter cell separation once the division process is completed, autolysis and biofilm formation. In particular, the CHAP PGHs Sle1 and SAUSA300_2253 control intracellular staphylococcal replication and the resistance to β-lactam antibiotics like oxacillin. This makes the S. aureus PGHs in general, and the Sle1 and SAUSA300_2253 proteins in particular, attractive targets for future prophylactic or therapeutic anti-staphylococcal interventions. Alternatively, these cell surface-exposed enzymes, or particular domains of these enzymes, could be applied in innovative anti-staphylococcal therapies.
期刊介绍:
Pathogen genome sequencing projects have provided a wealth of data that need to be set in context to pathogenicity and the outcome of infections. In addition, the interplay between a pathogen and its host cell has become increasingly important to understand and interfere with diseases caused by microbial pathogens. IJMM meets these needs by focussing on genome and proteome analyses, studies dealing with the molecular mechanisms of pathogenicity and the evolution of pathogenic agents, the interactions between pathogens and host cells ("cellular microbiology"), and molecular epidemiology. To help the reader keeping up with the rapidly evolving new findings in the field of medical microbiology, IJMM publishes original articles, case studies and topical, state-of-the-art mini-reviews in a well balanced fashion. All articles are strictly peer-reviewed. Important topics are reinforced by 2 special issues per year dedicated to a particular theme. Finally, at irregular intervals, current opinions on recent or future developments in medical microbiology are presented in an editorial section.