Enhanced fatty acid biosynthesis by Sigma28 in stringent responses contributes to multidrug resistance and biofilm formation in <i>Helicobacter pylori</i>
Junyuan Xue, Shutong Li, Liyuan Wang, Yican Zhao, Lu Zhang, Yantong Zheng, Wenxin Zhang, Zhenghong Chen, Ting Jiang, Yundong Sun
Abstract
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 (σ 28 ). 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.