Resistance to Mucosal Lysozyme Compensates for the Fitness Deficit of Peptidoglycan Modifications by Streptococcus pneumoniae

PLoS Pathogens

Jeffrey N. Weiser¹  Alistair J. Standish¹  Kimberly M. Davis¹  Henry T. Akinbi² 

[1] Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America;Divisions of Pulmonary Biology and Neonatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America

关键词: Peptidoglycans;    Neutrophils;    Antimicrobial resistance;    Cell walls;    Pneumococcus;    Mutant strains;    Chickens;    Mouse models;   

DOI  :  10.1371/journal.ppat.1000241

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The abundance of lysozyme on mucosal surfaces suggests that successful colonizers must be able to evade its antimicrobial effects. Lysozyme has a muramidase activity that hydrolyzes bacterial peptidoglycan and a non-muramidase activity attributable to its function as a cationic antimicrobial peptide. Two enzymes (PgdA, a N-acetylglucosamine deacetylase, and Adr, an O-acetyl transferase) that modify different sites on the peptidoglycan of Streptococcus pneumoniae have been implicated in its resistance to lysozyme in vitro. Here we show that the antimicrobial effect of human lysozyme is due to its muramidase activity and that both peptidoglycan modifications are required for full resistance by pneumococci. To examine the contribution of lysozyme and peptidoglycan modifications during colonization of the upper respiratory tract, competition experiments were performed with wild-type and pgdAadr mutant pneumococci in lysozyme M-sufficient (LysM+/+) and -deficient (LysM−/−) mice. The wild-type strain out-competed the double mutant in LysM+/+, but not LysM−/− mice, indicating the importance of resistance to the muramidase activity of lysozyme during mucosal colonization. In contrast, strains containing single mutations in either pgdA or adr prevailed over the wild-type strain in both LysM+/+ and LysM−/− mice. Our findings demonstrate that individual peptidoglycan modifications diminish fitness during colonization. The competitive advantage of wild-type pneumococci in LysM+/+ but not LysM−/− mice suggests that the combination of peptidoglycan modifications reduces overall fitness, but that this is outweighed by the benefits of resistance to the peptidoglycan degrading activity of lysozyme.

【 授权许可】

CC BY