Variation in Streptococcus pneumoniae susceptibility to human antimicrobial peptides may mediate intraspecific competition

Abstract

Streptococcus pneumoniae is a facultative pathogen inhabiting the nasopharynx of humans where it is exposed to a range of antimicrobial peptides (AMPs) of the innate immune response. It is possible therefore that the susceptibility of strains to AMPs plays a role in determining their ability to colonize, and furthermore, that AMPs could mediate competitive interactions between co-colonizing genotypes. However, little is known about patterns of natural variation in AMP susceptibility of S. pneumoniae, and it is unclear whether the susceptibilities of an isolate to multiple human AMPs are correlated. We tested this by characterizing the susceptibility of 31 S. pneumoniae natural isolates to human neutrophil peptide (HNP-1) (a-defensin) and LL-37 (cathelicidin). We observed significant variation in susceptibility between isolates to both AMPs, and in the majority of isolates, susceptibilities to HNP-1 and LL-37 were uncorrelated. Clinical isolates were more susceptible to AMPs than were carriage isolates. The polysaccharide capsule of S. pneumoniae is thought to protect cells against AMPs. However, serotype alone could not explain the observed variation in susceptibility suggesting that genetic background plays an equally important role. We tested directly whether AMPs could mediate competition between isolates using competition experiments in the presence and absence of AMPs. These experiments demonstrated that AMPs could indeed reverse the outcome of competition between selected isolates. AMP-mediated competition could therefore contribute to the maintenance of intraspecific genetic diversity in S. pneumoniae.

Large scale genomic analysis shows no evidence for pathogen adaptation between the blood and cerebrospinal fluid niches during bacterial meningitis

“…This suggests that interaction with host AMPs changes upon shift from the nasopharynx to the invasive niche, a notion that is supported by in vitro observations that clinical isolates of S. pneumoniae are more susceptible to AMPs than carriage isolates [31]. We observed an excess of damaging mutations in dlt compared to other loci.…”

Cationic antimicrobial peptide resistance mechanisms of streptococcal pathogens

“…While mechanisms of resistance to cathelicidin/LL-37 or defensins do not always correlate with one another [17], many of the virulence factors the pathogens employ to evade one CAMP can be cross protective against others. Nearly any virulence factor of a pathogen may contribute, at least indirectly, to a pathogen's resistance or susceptibility to CAMPs.…”

Comparing Selection on S. aureus between Antimicrobial Peptides and Common Antibiotics

“…Salmonella enterica can evolve resistance to protamine and PR-39, and costs of resistance were either not observable or reversible by compensatory mutation [5], [9]. Nevertheless, susceptibility is variable in natural isolates [10]. AMP resistance thus presents a puzzling paradox: selection for resistance is widespread and it can arise at low cost, so why does variation persist?…”