Group A streptococci induce stronger M protein-fibronectin interaction when specific human antibodies are bound

• DOI: 10.3389/fmicb.2023.1069789
• Publication Date: 2023-01-26T05:54:35Z
• Authors: Sebastian Wrighton; Vibha Kumra Ahnlide; Oscar André; Wael Bahnan; Pontus Nordenfelt
• Keywords: group A – beta hemolytic streptococcus; 0301 basic medicine; 03 medical and health sciences; fibronectin; antibodies; immune subversion; adaptive immunity; co-evolution; Microbiology; QR1-502; 3. Good health

Group A streptococcus (GAS) is a highly adapted, human-specific pathogen that known to manipulate the immune system through various mechanisms. GAS' M protein constitutes primary target of due its spatial configuration and dominance on bacterial surface. Antibody responses targeting have been shown favor conserved C region. Such antibodies (Abs) circumvent antigenic escape efficiently bind types. The ability GAS fibronectin (Fn), high molecular weight glycoprotein extracellular matrix, has long be essential for pathogen's evolutionary success fitness. However, some strains lack Fn. Instead, they found additionally Fn via A-B domains their proteins. Here, we show human Abs can induce increased Fn-binding affinity in proteins, likely by enhancing weak domain binding. We this enhanced binding leads reduction Ab-mediated phagocytosis, indicating mechanism. could Fc necessary trigger phenomenon Ab flexibility may also play key role. We, moreover, saw our enhance 3 out 5 emm type tested, belonging different clades, making it more generalizable phenomenon. Together results suggest novel synergistic interplay host proteins which ultimately benefits bacterium.