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

For many successful pathogens, their surfaces must be able to adapt to different host environments, or to avoid host immune components, to establish infection. Bacterial pathogens, for example, are known to modify their cell walls, which are comprised largely of peptidoglycan. 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. Two proteins (PgdA and Adr) that modify the cell wall of S. pneumoniae have each been associated with resistance to lysozyme, which cleaves peptidoglycan and is one of the most abundant antimicrobial factors in the human respiratory tract. Using defined bacterial mutants together with mice that express or lack lysozyme, we show that the full resistance to lysozyme requires modifications by both proteins. These cell wall modifications each come at a significant fitness cost to the bacterium. This fitness cost, however, is outweighed by the benefits of lysozyme resistance in vivo. Our study, therefore, demonstrates the relationship between a bacterial pathogen and a host defense mechanism that imparts a substantial selective pressure on organisms that colonize the mucosal surface.