Host serum amyloid A1 facilitates Streptococcus pneumoniae adaptation to acidic stress induced by pneumococcal anaerobic metabolism

Serum amyloid A1 (SAA1), an acute-phase protein, exhibits a decreased level in bronchoalveolar lavage fluid (BALF) following nasal Streptococcus pneumoniae infections. However, the function of SAA1 in relation to S. pneumoniae remains to be unclear. In this study, we investigate whether S. pneumoniae utilized SAA1 for its survival in host or not. We explored the function of SAA1 in relation to S. pneumoniae by initially comparing serum with high SAA1 levels to serum with low SAA1 levels. We then validated our findings using recombinant SAA1. In this research, we developed an original PBS-based intranasal administration method to induce SAA1 increases in serum. This innovative approach provides a convenient platform for studying the role of SAA1 in various bacterial species. In vitro experiments showed that when serum-THY broth was incubated with S. pneumoniae , a similar reduction in SAA1 was observed, which was proved to be independent of protease activity. Intake of AF488 (green-fluorescent probe)-conjugated recombinant SAA1 by S. pneumoniae was observed using fluoresence microscope. Then, we proved that intake of SAA1 enhanced S. pneumoniae resistance against formate, a key metabolite of its anaerobic metabolism. This study is the first to reveal the relationship between SAA1 and a Gram-positive bacterium. We demonstrate that S. pneumoniae exploits host acute-phase proteins to enhance its survival in formic acidic environments. These findings expand our understanding of bacterial survival strategies, highlighting how pathogens utilize host-derived components to adapt to hostile conditions.