Up-expression of NapA and other oxidative stress proteins is a compensatory response to loss of major Helicobacter pylori stress resistance factors.
Twenty-six Helicobacter pylori targeted mutant strains with deficiencies in oxidative stress combating proteins, including 12 double mutant strains were analyzed via physiological and proteomic approaches to distinguish the major expression changes caused by the mutations. Mutations were introduced into both a Mtz(S) and a Mtz(R) strain background. Most of the mutations caused increased growth sensitivity of the strains to oxygen, and they all exhibited clear compensatory up-expression of oxidative stress resistance proteins enabling survival of the bacterium. The most frequent up-expressed oxidative stress resistance factor (observed in 16 of the mutants) was the iron-sequestering protein NapA, linking iron sequestration with oxidative stress resistance. The up-expression of individual proteins in mutants ranged from 2 to 10 fold that of the wild type strain, even when incubated in a low O(2) environment. For example, a considerably higher level of catalase expression (4 fold of that in the wild-type strain) was observed in ahpC napA and ahpC sodB double mutants. A Fur mutant up-expressed ferritin (Pfr) protein 20-fold. In some mutant strains the bacterial DNA is protected from oxidative stress damage apparently via overexpression of oxidative stress-combating proteins such as NapA, catalase or MdaB (an NADPH quinone reductase). Our results show that H. pylori has a variety of ways to compensate for loss of major oxidative stress combating factors.
Olczak
Adriana A
AA
Department of Microbiology, University of Georgia, Athens, 30602, USA.
Wang
Ge
G
Maier
Robert J
RJ
D000135:Acid Phosphatase / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D053938:DNA Fragmentation; D019008:Drug Resistance, Neoplasm; D004587:Electrophoresis, Agar Gel; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D005293:Ferritins / Q000737:chemistry; D006360:Heat-Shock Proteins / Q000378:metabolism; D016481:Helicobacter Infections / Q000378:metabolism; D016480:Helicobacter pylori / Q000378:metabolism*; D017665:Hydroxyl Radical; D007501:Iron / Q000378:metabolism; D008795:Metronidazole / Q000494:pharmacology; D051379:Mice; D009154:Mutation; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D011815:R Factors / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; C095690:MdaB protein, E coli; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; C431650:pfr protein, Helicobacter pylori; D008795:Metronidazole; D017665:Hydroxyl Radical; D004247:DNA; D005293:Ferritins; D007501:Iron; D002374:Catalase; D000135:Acid Phosphatase; C092729:NapA phosphatase; D010100:Oxygen