Glucose Induces Resistance to Polymyxins in High-Alcohol-Producing Klebsiella pneumoniae via Increasing Capsular Polysaccharide and Maintaining Intracellular ATP

• DOI: 10.1128/spectrum.00031-23
• Publication Date: 2023-06-20T14:01:01Z
• Authors: Zheng Fan; Tongtong Fu; Hongbo Liu; Zhoufei Li; Bing Du; Xiaohu Cui; Rui Zhang; Yanling Feng; Hanqing Zhao; Guanhua Xue; Jinghua Cui; Chao Yan; Lin Gan; Junxia Feng; Ziying Xu; Zihui Yu; Ziyan Tian; Zanbo Ding; Jinfeng Chen; Yujie Chen; Jing Yuan
• Keywords: Polymyxin

High-alcohol-producing K. pneumoniae (HiAlc Kpn) causes nonalcoholic fatty liver disease (NAFLD) by producing excess endogenous alcohol in the gut of patients with NAFLD, using glucose as main carbon source. The role response HiAlc Kpn to environmental stresses such antibiotics remains unclear. In this study, we found that could enhance resistance polymyxins. First, inhibited expression crp and promoted increase capsular polysaccharide (CPS), which drug Kpn. Second, maintained high ATP levels cells under pressure polymyxins, enhancing killing effect antibiotics. Notably, inhibition CPS formation decrease intracellular both effectively reverse glucose-induced polymyxins resistance. Our work demonstrated mechanism induces Kpn, thereby laying foundation for developing effective treatments NAFLD caused IMPORTANCE can use produce promoting development NAFLD. Polymyxins are last line commonly used treat infections carbapenem-resistant pneumoniae. increased bacterial via increasing maintaining ATP; increases risk failure multidrug-resistant infection. Further research revealed important roles global regulator, CRP, inhibiting decreasing reveals regulatory factor CRP affect bacteria a treatment bacteria.