resistance to mucosal lysozyme compensates for the fitness deficit of peptidoglycan modifications by streptococcus pneumoniae抗粘膜溶菌酶补偿健身赤字由肺炎链球菌肽聚糖的修改.pdfVIP

Resistance to Mucosal Lysozyme Compensates for the Fitness Deficit of Peptidoglycan Modifications by Streptococcus pneumoniae 1 2 1 1 Kimberly M. Davis , Henry T. Akinbi , Alistair J. Standish , Jeffrey N. Weiser * 1 Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America, 2 Divisions of Pulmonary Biology and Neonatology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America 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 (LysM2/ 2) mice. The wild-type strain out-competed the double mutant in LysM+/+, but not LysM2/ 2 mice, indicating the importance of resistance to the muramidase activity of lysozyme during mucosal co