Bubonic plague is transmitted by fleas whose feeding is blocked by a Yersinia pestis biofilm in the digestive tract. Y. pestis also block feeding of Caenorhabditis elegans by forming a biofilm on the nematode head, making the nematode an experimentally tractable surrogate for fleas to study plague transmission. Arabinose 5-phosphate isomerase (API), encoded by Y. pestis yrbH, catalyses the conversion of ribulose 5-phosphate into arabinose 5-phosphate (A5P), the first committed step in the 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) biosynthesis pathway. Here we show that Y. pestis YrbH is a multifunctional protein required for both Kdo biosynthesis and biofilm formation on C. elegans. The YrbH protein contains four functional components: biofilm-related region 1 (B1), a sugar isomerase domain (SIS), biofilm-related region 2 (B2) and a cystathionine β-synthase domain pair (CBS). B1, SIS and B2 are all required for API function, but any of the three is sufficient for a biofilm-related function. The CBS domain appears to negatively regulate the biofilm-related function.