Effect of the crp mutation on the utilization of transferrin-bound iron by Vibrio vulnificus.
Cyclic AMP-cAMP receptor protein (CRP) complex plays an essential role in the global regulation of Vibrio vulnificus virulence. We found that growth retardation of V. vulnificus caused by mutation of the crp gene encoding CRP was exacerbated under iron-limited conditions. Accordingly, we investigated the effect of crp mutation on the expression of the vulnibactin-mediated iron-uptake system and the ability of V. vulnificus to utilize transferrin-bound iron, and thus to grow in cirrhotic ascites, a human ex vivo system. The production of vulnibactin was suppressed, and the transcription of the vis and vuuA genes, which encode an enzyme required for vulnibactin synthesis and vulnibactin receptor protein, was also suppressed in the crp mutant. Moreover, the crp mutant could not utilize transferrin-bound iron, and its growth was severely suppressed both on transferrin-bound iron and in cirrhotic ascites. All the defects in the crp mutant were recovered by the in trans complementation of the wild-type crp gene. Putative CRP-binding sequences were found in the regulatory regions of the fur, vis and vuuA genes. These results indicate that crp mutation attenuates the ability to grow on transferrin-bound iron and in a human body fluid by down-regulating the vulnibactin-mediated iron-uptake system.
Choi
Mi-Hwa
MH
Research Center for Resistant Cells, Chosun University Medical School, Gwangju, Korea.
Sun
Hui-Yu
HY
Park
Ra-Young
RY
Kim
Choon-Mee
CM
Bai
Young-Hoon
YH
Kim
Young-Ran
YR
Rhee
Joon-Haeng
JH
Shin
Sung-Heui
SH
D000577:Amides / Q000378:metabolism; D001202:Ascitic Fluid; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D003470:Culture Media; D015536:Down-Regulation; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010080:Oxazoles / Q000378:metabolism; D011953:Receptors, Cyclic AMP / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D017262:Siderophores / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism*; D041261:Vibrio vulnificus / Q000254:growth & development / Q000378:metabolism*
D000577:Amides; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D003470:Culture Media; C063931:Omp2 protein, bacteria; D010080:Oxazoles; D011953:Receptors, Cyclic AMP; D012097:Repressor Proteins; D017262:Siderophores; D014168:Transferrin; C068477:ferric uptake regulating proteins, bacterial; C086667:vulnibactin; D007501:Iron