K. Skorupski et Rk. Taylor, CYCLIC-AMP AND ITS RECEPTOR PROTEIN NEGATIVELY REGULATE THE COORDINATE EXPRESSION OF CHOLERA-TOXIN AND TOXIN-COREGULATED PILUS IN VIBRIO-CHOLERAE, Proceedings of the National Academy of Sciences of the United Statesof America, 94(1), 1997, pp. 265-270
Insertion mutations in two Vibrio cholerae genes, cya and crp, which e
ncode adenylate cyclase and the cyclic AMP (cAMP) receptor protein (CR
P), respectively, derepressed the expression of a chromosomal cholera
toxin (CT) promoter-lacZ fusion at the nonpermissive temperature of 37
degrees C. In the classical biotype strain O395, the crp mutation inc
reased the production of both CT and toxin-coregulated pilus (TCP) in
vitro under a variety of growth conditions not normally permissive for
their expression. The most dramatic increase in CT and TCP was observ
ed with the crp mutant in Luria-Bertani (LB) medium pH 8.5, at 30 degr
ees C. El Tor biotype strains differ from classical strains in that th
ey do not produce CT or TCP when grown in LB media. Incorporation of t
he crp mutation into El Tor strain C6706 permitted production of these
proteins in LB medium pH 6.5, at 30 degrees C. In the infant mouse ch
olera model, the crp mutation decreased colonization in both biotypes
at least 100-fold relative to the wild-type strains. The data presente
d here suggest a model whereby cAMP-CRP negatively regulates the expre
ssion of CT and TCP in both classical and El Tor biotypes under certai
n environmental conditions and also influences pathogenesis by regulat
ing other processes necessary for optimal growth in vivo.