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

Ankur B. Dalia and Jeffery N. Weiser., 2011. Cell host & microbe. 10(5):486-96.

Speaker: Po-Sheng Tsai (蔡伯昇)                                  Time: 13:00~14:00, Dec. 26, 2012

Commentator: Dr. Shu-Ying Wang (王淑鶯老師)               Place: Room 601

Abstract

A critical strategy that the host uses to control microbial infections is the complement system, which can lead to lysis of gram-negative bacteria and opsonophagocytosis (OPH) of gram-positive bacteria. However, Streptococcus pneumoniae (pneumococcus), a leading cause of invasive bacterial infection, uses numerous strategies to resist killing by this mechanism. Previous studies have shown that pneumococci can mask underlying structures with surface capsular polysaccharide and interaction with serum components by surface proteins to evade complement activation. To search for additional factors promoting resistance to OPH, they screened a genomic library of pneumococcal mutants to identify an OPH-sensitive phenotype. The results suggested that an increase in bacterial chain length (CL) decreases resistance to OPH. The relationship between CL and resistance to OPH was dissected by comparing three aspects among pneumococci which differ in CL. The results show that pneumococci which form longer CL have less survival through OPH, more uptake by neutrophils, and more C3 deposition on their surface. This indicates that longer CL leads to increased likelihood of attaining a complement-activating focus, which can then deposit and spread C3 throughout the bacterial chain. Further, longer CL can enhance susceptibility to uptake by phagocytes, and killing in the phagolysosome. On the other hand, lower CL can provide bacteria with a competitive advantage in resisting this clearance mechanism. To overcome this complement evasion strategy, the authors found that agglutination induced by antibodies is similar to an increase in CL by amassing bacteria together as shown by previous research. Thus, they examined whether bacterial agglutination can promote OPH by comparing the survival rate between bacteria incubated with IgG fragment F(ab’)₂ and Fab. Data show that F(ab’)₂ which can agglutinate bacteria triggers OPH and results in lower survival rate than Fab, indicating that bacteria in larger aggregates are more susceptible to complement deposition. In summary, this study shows that the chain of pneumococci which are smaller in size are more likely to evade OPH killing, and that virulence strategy can be subverted by antibody-mediated agglutination.

References:

1.      O’Brien et al., Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. 2009. Lancet 374:893–902.