Enhanced fatty acid biosynthesis by Sigma28 in stringent responses contributes to multidrug resistance and biofilm formation in Helicobacter pylori.
Antimicrob Agents Chemother
; 68(9): e0085024, 2024 Sep 04.
Article
em En
| MEDLINE
| ID: mdl-39046242
ABSTRACT
The metabolic state of bacteria significantly contributes to their resistance to antibiotics; however, the specific metabolic mechanisms conferring antimicrobial resistance in Helicobacter pylori remain largely understudied. Employing transcriptomic and non-targeted metabolomics, we characterized the metabolic reprogramming of H. pylori when challenged with antibiotic agents. We observed a notable increase in both genetic and key proteomic components involved in fatty acid biosynthesis. Inhibition of this pathway significantly enhanced the antibiotic susceptibility of the sensitive and multidrug-resistant H. pylori strains while also disrupting their biofilm-forming capacities. Further analysis revealed that antibiotic treatment induced a stringent response, triggering the expression of the hp0560-hp0557 operon regulated by Sigma28 (σ28). This activation in turn stimulated the fatty acid biosynthetic pathway, thereby enhancing the antibiotic tolerance of H. pylori. Our findings reveal a novel adaptive strategy employed by H. pylori to withstand antibiotic stress.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
/
Helicobacter pylori
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Biofilmes
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Farmacorresistência Bacteriana Múltipla
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Ácidos Graxos
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Antibacterianos
Idioma:
En
Revista:
Antimicrob Agents Chemother
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Estados Unidos