Inverse nickel-responsive regulation of two urease enzymes in the gastric pathogen Helicobacter mustelae.
The acidic gastric environment of mammals can be chronically colonized by pathogenic Helicobacter species, which use the nickel-dependent urea-degrading enzyme urease to confer acid resistance. Nickel availability in the mammal host is low, being mostly restricted to vegetarian dietary sources, and thus Helicobacter species colonizing carnivores may be subjected to episodes of nickel deficiency and associated acid sensitivity. The aim of this study was to investigate how these Helicobacter species have adapted to the nickel-restricted diet of their carnivorous host. Three carnivore-colonizing Helicobacter species express a second functional urea-degrading urease enzyme (UreA2B2), which functions as adaptation to nickel deficiency. UreA2B2 was not detected in seven other Helicobacter species, and is in Helicobacter mustelae only expressed in nickel-restricted conditions, and its expression was higher in iron-rich conditions. In contrast to the standard urease UreAB, UreA2B2 does not require activation by urease or hydrogenase accessory proteins, which mediate nickel incorporation into these enzymes. Activity of either UreAB or UreA2B2 urease allowed survival of a severe acid shock in the presence of urea, demonstrating a functional role for UreA2B2 in acid resistance. Pathogens often express colonization factors which are adapted to their host. The UreA2B2 urease could represent an example of pathogen adaptation to the specifics of the diet of their carnivorous host, rather than to the host itself.
Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center, 's Gravendijkwal 230, 3015 CE Rotterdam, the Netherlands.
Jeroen
J
Stoof
Simone
S
Breijer
Raymond G J
RG
Pot
Daan
D
van der Neut
Ernst J
EJ
Kuipers
Johannes G
JG
Kusters
Arnoud H M
AH
van Vliet
D000143:Acids / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004790:Enzyme Induction; D020869:Gene Expression Profiling; D023061:Gene Order; D045502:Helicobacter mustelae / Q000187:drug effects / Q000201:enzymology*; D050296:Microbial Viability; D009532:Nickel / Q000378:metabolism*; D009876:Operon; D014510:Urease / Q000096:biosynthesis*
D000143:Acids; D000900:Anti-Bacterial Agents; D009532:Nickel; D014510:Urease