Minimization of Bacterial Size Allows for Complement Evasion and Is Overcome by the Agglutinating Effect of Antibody

Abstract

SUMMARY The complement system, which functions by lysing pathogens directly or by promoting their uptake by phagocytes, is critical for controlling many microbial infections. Here we show that in Streptococcus pneumoniae, increasing bacterial chain length sensitizes this pathogen to complement deposition and subsequent uptake by human neutrophils. Consistent with this, we show that minimizing chain length provides wild-type bacteria with a competitive advantage in vivo in a model of systemic infection. Investigating how the host overcomes this virulence strategy, we find that antibody promotes complement-dependent opsonophagocytic killing of Streptococcus pneumoniae and lysis of Haemophilus influenzae independent of Fc-mediated effector functions. Consistent with the agglutinating effect of antibody, F(ab′)2 but not Fab could promote this effect. Therefore, increasing pathogen size, whether by natural changes in cellular morphology or via antibody-mediated agglutination, promotes complement-dependent killing. These observations have broad implications for how cell size and morphology can affect virulence among pathogenic microbes.

Staying in Shape: the Impact of Cell Shape on Bacterial Survival in Diverse Environments

“…One intriguing observation is that several common invasive pathogens are relatively small, including S. pneumoniae, N. meningitidis, and Haemophilus influenzae (80,110). Indeed, microbial cell size is an important pathogenesis factor, and work by Dalia and Weiser demonstrated that minimization of bacterial size is a mechanism used by S. pneumoniae to circumvent complement-mediated killing by the host (110). They found that during invasive systemic infection, S. pneumoniae cells with decreased chain length were more virulent than their corresponding long-chain variants (110).…”

“…Indeed, microbial cell size is an important pathogenesis factor, and work by Dalia and Weiser demonstrated that minimization of bacterial size is a mechanism used by S. pneumoniae to circumvent complement-mediated killing by the host (110). They found that during invasive systemic infection, S. pneumoniae cells with decreased chain length were more virulent than their corresponding long-chain variants (110). Longer bacterial chains collectively possess a larger surface area and thus serve as larger targets for complement deposition and opsonophagocytic killing (110).…”

Bacterial exploitation of phosphorylcholine mimicry suppresses inflammation to promote airway infection

“…Mutants lacking ChoP esterase (Δpce) were derived for each strain from an insertion-duplication mutant (56) and used for all experiments except where specified. Independently, we created an in-frame, unmarked Δpce-deletion mutant and a genetically corrected revertant (Δpce::pce) by previously described methods (41). Refer to the Supplemental Methods for details and to Supplemental Table 1 for primers used in mutagenesis.…”

Wzy-Dependent Bacterial Capsules as Potential Drug Targets

“…While numerous virulence factors undoubtedly contribute to the pathogen's ability to resist complement deposition and phagocytosis [23][24][25], two recent studies have illustrated the central dominance of the capsule in this strategy [24,26]. Both of these studies showed the fundamental importance of capsule by leaving the genetic background the same and only changing the capsule type.…”