A Positively Selected fur-R88H Mutation Enhances Helicobacter pylori Fitness in a High-Salt Environment and Alters Fur-Dependent Regulation of Gene Expression.
Infect Immun
; 91(2): e0042022, 2023 02 16.
Article
em En
| MEDLINE
| ID: mdl-36633416
ABSTRACT
Both Helicobacter pylori infection and a high-salt diet are risk factors for gastric cancer. We previously showed that a mutation in fur (encoding the ferric uptake regulator variant Fur-R88H) was positively selected in H. pylori strains isolated from experimentally infected Mongolian gerbils receiving a high-salt diet. In the present study, we report that continuous H. pylori growth in high-salt conditions in vitro also leads to positive selection of the fur-R88H mutation. Competition experiments with strains containing wild-type fur or fur-R88H, each labeled with unique nucleotide barcodes, showed that the fur-R88H mutation enhances H. pylori fitness under high-salt conditions but reduces H. pylori fitness under routine culture conditions. The fitness advantage of the fur-R88H mutant under high-salt conditions was abrogated by the addition of supplemental iron. To test the hypothesis that the fur-R88H mutation alters the regulatory properties of Fur, we compared the transcriptional profiles of strains containing wild-type fur or fur-R88H. Increased transcript levels of fecA2, which encodes a predicted TonB-dependent outer membrane transporter, were detected in the fur-R88H variant compared to those in the strain containing wild-type fur under both high-salt and routine conditions. Competition experiments showed that fecA2 contributes to H. pylori fitness under both high-salt and routine conditions. These results provide new insights into mechanisms by which the fur-R88H mutation confers a selective advantage to H. pylori in high-salt environments.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Proteínas de Bactérias
/
Helicobacter pylori
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Infect Immun
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos