Abstract
Bacterial pathogens produce complex carbohydrate capsules to protect against bactericidal immune molecules. Paradoxically, the pneumococcal capsule sensitizes the bacterium to antimicrobial peptides found on epithelial surfaces. Here we show that upon interaction with antimicrobial peptides, encapsulated pneumococci survive by removing capsule from the cell surface within minutes in a process dependent on the suicidal amidase autolysin LytA. In contrast to classical bacterial autolysis, during capsule shedding, LytA promotes bacterial survival and is dispersed circumferentially around the cell. However, both autolysis and capsule shedding depend on the cell wall hydrolytic activity of LytA. Capsule shedding drastically increases invasion of epithelial cells and is the main pathway by which pneumococci reduce surface bound capsule during early acute lung infection of mice. The previously unrecognized role of LytA in removing capsule to combat antimicrobial peptides may explain why nearly all clinical isolates of pneumococci conserve this enzyme despite the lethal selective pressure of antibiotics.
Highlights
Bacterial pathogens produce complex carbohydrate capsules to protect against bactericidal immune molecules
We show here that exposure to cationic antimicrobial peptides (CAMPs) leads to the accumulation of pneumococcal capsule in the supernatant of cultures, and that growth in a CAMP-rich environment can lead to almost complete loss of surface capsule
Similar to a previous report[11], that growth of encapsulated bacteria was inhibited by LL-37 at 16 and 32 mg ml À 1, whereas a mutant producing no capsule was not inhibited at these concentrations (Fig. 1a)
Summary
Bacterial pathogens produce complex carbohydrate capsules to protect against bactericidal immune molecules. We show that upon interaction with antimicrobial peptides, encapsulated pneumococci survive by removing capsule from the cell surface within minutes in a process dependent on the suicidal amidase autolysin LytA. As with most Gram-positive pathogens, the pneumococcal capsule is thought to be covalently linked to the peptidoglycan of the cell wall in most strains, though the specific nature of the attachment has remained elusive[1]; it is clear that in different host tissues, such as epithelial surfaces, the pneumococcus can rapidly reduce encapsulation through unknown mechanisms[2]. Capsule has dual roles in the response of pneumococci to CAMPs, sensitizing those strains that are making capsule to bactericidal effects, while purified capsule has the ability to protect unencapsulated strains from unbound antimicrobial peptide in the environment. Our results reveal a novel pathway for removal of surface-associated capsule that is both protective against the bactericidal effects of CAMPs and provides the first molecular mechanism for the loss of capsule observed when bacteria contact epithelial surfaces
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