Role of GacA in virulence of Vibrio vulnificus.
The GacS/GacA two-component signal transduction system regulates virulence, biofilm formation and symbiosis in Vibrio species. The present study investigated this regulatory pathway in Vibrio vulnificus, a human pathogen that causes life-threatening disease associated with the consumption of raw oysters and wound infections. Small non-coding RNAs (csrB1, csrB2, csrB3 and csrC) commonly regulated by the GacS/GacA pathway were decreased (P<0.0003) in a V. vulnificus CMCP6 ΔgacA : : aph mutant compared with the wild-type parent, and expression was restored by complementation of the gacA deletion mutation in trans. Of the 20 genes examined by RT-PCR, significant reductions in the transcript levels of the mutant in comparison with the wild-type strain were observed only for genes related to motility (flaA), stationary phase (rpoS) and protease (vvpE) (P=0.04, 0.01 and 0.002, respectively). Swimming motility, flagellation and opaque colony morphology indicative of capsular polysaccharide (CPS) were unchanged in the mutant, while cytotoxicity, protease activity, CPS phase variation and the ability to acquire iron were decreased compared with the wild-type (P<0.01). The role of gacA in virulence of V. vulnificus was also demonstrated by significant impairment in the ability of the mutant strain to cause either skin (P<0.0005) or systemic infections (P<0.02) in subcutaneously inoculated, non-iron-treated mice. However, the virulence of the mutant was equivalent to that of the wild-type in iron-treated mice, demonstrating that the GacA pathway in V. vulnificus regulates the virulence of this organism in an iron-dependent manner.
Gauthier
Julie D
JD
Department of Biological Sciences, Loyola University, New Orleans, LA 70118, USA.|Food Science and Human Nutrition Department, 212 Aquatic Food Products Laboratory, University of Florida, Gainesville, FL 32611, USA.
Jones
Melissa K
MK
Food Science and Human Nutrition Department, 212 Aquatic Food Products Laboratory, University of Florida, Gainesville, FL 32611, USA.
Thiaville
Patrick
P
Molecular Genetics and Microbiology Department, R1-144 Academic Research Building, University of Florida, Gainesville, FL 32611, USA.
Joseph
Jennifer L
JL
Molecular Genetics and Microbiology Department, R1-144 Academic Research Building, University of Florida, Gainesville, FL 32611, USA.
Swain
Rick A
RA
Food Science and Human Nutrition Department, 212 Aquatic Food Products Laboratory, University of Florida, Gainesville, FL 32611, USA.
Krediet
Cory J
CJ
Soil and Water Science Department, 330E Genetics Institute, University of Florida, Gainesville, FL 32611, USA.
Gulig
Paul A
PA
Molecular Genetics and Microbiology Department, R1-144 Academic Research Building, University of Florida, Gainesville, FL 32611, USA.
Teplitski
Max
M
Soil and Water Science Department, 330E Genetics Institute, University of Florida, Gainesville, FL 32611, USA.
Wright
Anita C
AC
Food Science and Human Nutrition Department, 212 Aquatic Food Products Laboratory, University of Florida, Gainesville, FL 32611, USA.
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D014735:Vibrio Infections / Q000382:microbiology*; D041261:Vibrio vulnificus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D014774:Virulence
D001426:Bacterial Proteins; C091100:GacA protein, Bacteria; D007501:Iron