Regulation of capsule biosynthesis in serotype A strains of Pasteurella multocida

The capsule of Pasteurella multocida serotype A strain ATCC 11039 is composed of hyaluronic acid and is an important virulence factor. Repeated subculturing of certain capsular serotype A strains results in dissociation from a capsulated to a noncapsulated phenotype with a concomitant loss of virulence. Although noncapsulated variants have been thought to arise as a result of mutation, the molecular mechanisms underlying this event are unknown. In this study, we demonstrate that restoration of the capsulated phenotype occurs in vivo subsequent to intraperitoneal inoculation of BALB/c mice with a noncapsulated variant. Moreover, reverse transcription polymerase chain reaction analysis revealed the capsule locus to be under transcriptional control. Cloning and sequencing of a 290-bp fragment within the promoter containing intergenic region of the capsule locus of 11039/iso revealed no significant alterations occurred subsequent to subculturing. These results demonstrate that serotype A P. multocida strain ATCC 11039 regulates capsule expression in response to an unidentified environmental factor(s), thereby providing insights into the molecular mechanisms underlying colonial dissociation.