Pyruvate formate lyase regulates fermentation metabolism and virulence of <i>Streptococcus suis</i>

<i>Streptococcus suis</i>, a zoonotic pathogen, is commonly found as a commensal bacterium in the respiratory tracts of pigs. Under specific conditions, it becomes invasive and enters the blood, causing severe systemic infections. For <i>S. suis</i>, effective acquisition of carbon sources in different host niches is necessary for its survival. However, as of now, our understanding of the metabolism of <i>S. suis</i> within the host is highly restricted. Pyruvate formate lyase (PFL) plays a crucial role in bacterial survival of in glucose-limited and hypoxic host tissues. Here, we investigated the physiological and metabolic functions of PFL PflB in <i>S. suis</i> and elucidated its pivotal role in regulating virulence within the mucosal and blood niches. We demonstrate that PflB is a key enzyme for <i>S. suis</i> to support mixed-acid fermentation under glucose-limited and hypoxic conditions. Additionally, PflB is involved in regulating <i>S. suis</i> morphology and stress tolerance, and its regulation of capsular polysaccharide content depends on dynamic carbon availability. We also found that PflB is associated with the capacity of <i>S. suis</i> to cause bacteremia and persist in the upper respiratory tract to induce persistent infection. Our results provide highly persuasive evidence for the relationship between metabolic regulation and the virulence of <i>S. suis</i>.