SignificanceIntestinal mucus forms an important protective barrier, preventing nonpathogenic bacteria from escaping the gut and damaging the cells that line it. We show that bacterial pathogens have evolved strategies to overcome this barrier by first migrating toward sialic acid, a sugar derived from mucus. Upon acquiring sialic acid, pathogens use it to fuel their growth and expansion in the gut. Sialic acid also induces the secretion of two key proteins that help these pathogens penetrate the mucus, as well as stick to the cells lining the gut. Correspondingly, a pathogen unable to sense or utilize sialic acid is significantly impaired in infecting its hosts or causing disease. Thus, the metabolism of sialic acid plays a key role in bacterial pathogenesis.