Pyruvate formate lyase regulates fermentation metabolism and virulence of .

, 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 , effective acquisition of carbon sources in different host niches is necessary for its survival. However, as of now, our understanding of the metabolism of 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 and elucidated its pivotal role in regulating virulence within the mucosal and blood niches. We demonstrate that PflB is a key enzyme for to support mixed-acid fermentation under glucose-limited and hypoxic conditions. Additionally, PflB is involved in regulating 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 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 .