PMID:10417643

Citation	Herrmann, L, Schwan, D, Garner, R, Mobley, HL, Haas, R, Schäfer, KP and Melchers, K (1999) Helicobacter pylori cadA encodes an essential Cd(II)-Zn(II)-Co(II) resistance factor influencing urease activity. Mol. Microbiol. 33:524-36
Abstract	Inactivation of Helicobacter pylori cadA, encoding a putative transition metal ATPase, was only possible in one of four natural competent H. pylori strains, designated 69A. All tested cadA mutants showed increased growth sensitivity to Cd(II) and Zn(II). In addition, some of them showed both reduced 63Ni accumulation during growth and no or impaired urease activity, which was not due to lack of urease enzyme subunits. Gene complementation experiments with plasmid (pY178)-derived H. pylori cadA failed to correct the deficiencies, whereas resistance to Cd(II) and Zn(II) was restored. Moreover, pY178 conferred increased Co(II) resistance to both the cadA mutants and the wild-type strain 69A. Heterologous expression of H. pylori cadA in an Escherichia coli zntA mutant resulted in an elevated resistance to Cd(II) and Zn(II). Expression of cadA in E. coli SE5000 harbouring H. pylori nixA, which encodes a divalent cation importer along with the H. pylori urease gene cluster, led to about a threefold increase in urease activity compared with E. coli control cells lacking the H. pylori cadA gene. These results suggest that H. pylori CadA is an essential resistance pump with ion specificity towards Cd(II), Zn(II) and Co(II). They also point to a possible role of H. pylori CadA in high-level activity of H. pylori urease, an enzyme sensitive to a variety of metal ions.
Links	PubMed
Keywords	Adenosine Triphosphatases/genetics; Adenosine Triphosphatases/metabolism; Bacterial Proteins/genetics; Biological Transport; Blotting, Western; Cadmium/chemistry; Cobalt/chemistry; Escherichia coli/genetics; Gene Expression Regulation, Bacterial; Genetic Complementation Test; Helicobacter pylori/enzymology; Helicobacter pylori/genetics; Metalloproteins/metabolism; Mutation; Plasmids/genetics; Urease/genetics; Urease/metabolism; Zinc/chemistry
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HELPY:HMCT		GO:0030001: metal ion transport	ECO:0000315:		P		Table 1: Growth of all four cadA mutants was at least 10- fold more sensitive to cadmium and zinc compared with the parental strain. This phenotype could be reversed by the H. pylori CadA expression vector pY178, as demonstrated for H. pylori 439-3[py178] and 13-9[pY178]. Additionally, strains harbouring plasmid pY178 grew in 10-fold to 20-fold higher concentrations of cobalt than the control strains. The increase in cobalt resistance corresponds to the elevated CadA protein content of strains carrying pY178. This evidence suggests that CadA is involved in the transport of these metal ions.	complete CACAO 6294
HELPY:HMCT	involved_in	GO:0030001: metal ion transport	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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