Abstract
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.
Highlights
IntroductionColonization of mucosal surfaces is a prerequisite for events leading to disease
For many pathogens, colonization of mucosal surfaces is a prerequisite for events leading to disease
Our study focuses on peptidoglycan modifications by Streptococcus pneumoniae, which initiates interaction with its host by colonizing the mucosal surface of the upper respiratory tract
Summary
Colonization of mucosal surfaces is a prerequisite for events leading to disease. At these sites the host elaborates numerous antimicrobial factors that may reduce the burden of colonizing organisms. Lysozyme has two distinct antibacterial activities [5,6]. An antibacterial activity is observed with catalytically inactive lysozyme [6]. This non-muramidase activity has been attributed to the disruption of bacterial membrane function by an inherent nine amino acid cationic antimicrobial peptide (CAMP) [5,7]
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