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

<i>Streptococcus suis</i>, a zoonotic pathogen, is commonly found as a commensal bacterium in the respiratory tract of pigs. Under specific conditions, it can become invasive and lead to severe life-threatening systemic infections in pigs, including bacteremia, endocarditis, toxic shock syndrome, and death. The transition from a symbiotic state to an invasive state is accompanied by the adaptation of bacteria to diverse host niches, which entails the efficient acquisition of host nutrients and dynamic regulation of metabolism. Pyruvate formate lyase plays a crucial role in bacterial survival in nutrition-limited and hypoxic host tissues. This study investigated the physiological and metabolic functions of pyruvate formate lyase in<i> S. suis</i> and elucidated its pivotal role in regulating virulence within the mucosal and blood niches of this pathogen. We identified PflB as a key enzyme that supports mixed acid fermentation under nutrition-limited and hypoxic conditions in <i>S. suis</i>. Additionally, PflB is involved in regulating <i>S. suis</i> morphology and adaptability to the environment, and its regulation of capsular polysaccharide production depends on dynamic carbon availability. The presence of PflB may be associated with the capacity of <i>S. suis</i> to persist in the upper respiratory tract and to induce persistent infection.