Inhibiting Peptidoglycan Hydrolase Alleviates MRSA Pneumonia Through Autolysin-Mediated MDP-NOD2 Pathway.

Background: (MRSA) is a cause of staph infection that is difficult to treat because of resistance to some antibiotics. A recent study indicated that diarylurea is a novel antibacterial agent against multi-drug resistant . In this work, we refined the bactericidal mechanism of as a peptidoglycan (PG) hydrolase by affecting AtlA-mediated PG homeostasis.

Methods: A wild-type strain (WT) and a mutant strain (Δ) were used to investigate the effects of on the cell wall, PG, and autolysin regulatory system by antimicrobial susceptibility testing, hemolytic toxin assay, microanalysis, autolysis assay, qRT-PCR, ELISA and mouse model of pneumonia.

Results: The results revealed that down-regulated the expression of genes related to peptidoglycan hydrolase (PGH) (, and ), and reduced the levels of PG, muramyl dipeptide (MDP), cytokines, and hemolytic toxin, while Δ interfered with the genes regulation and PG homeostasis. In the mouse MRSA pneumonia model, the same trend was observed in the nucleotide oligomerization domain protein 2 (NOD2) and relative proinflammatory factors.

Conclusion: may act as a novel inhibitor of PG hydrolyse, disrupting autolysin-mediated PG homeostasis, and reducing inflammation by down-regulating the MDP-NOD2 pathway.