Glucose Induces Resistance to Polymyxins in High-Alcohol-Producing Klebsiella pneumoniae via Increasing Capsular Polysaccharide and Maintaining Intracellular ATP
ABSTRACT 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 the main carbon source. The role of glucose in the response of HiAlc Kpn to environmental stresses such...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2023-08-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00031-23 |
| _version_ | 1797741758420877312 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Zheng Fan |
| collection | DOAJ |
| description | ABSTRACT 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 the main carbon source. The role of glucose in the response of HiAlc Kpn to environmental stresses such as antibiotics remains unclear. In this study, we found that glucose could enhance the resistance of HiAlc Kpn to polymyxins. First, glucose inhibited the expression of crp in HiAlc Kpn and promoted the increase of capsular polysaccharide (CPS), which promoted the drug resistance of HiAlc Kpn. Second, glucose maintained high ATP levels in HiAlc Kpn cells under the pressure of polymyxins, enhancing the resistance of the cells to the killing effect of antibiotics. Notably, the inhibition of CPS formation and the decrease of intracellular ATP levels could both effectively reverse glucose-induced polymyxins resistance. Our work demonstrated the mechanism by which glucose induces polymyxins resistance in HiAlc Kpn, thereby laying the foundation for developing effective treatments for NAFLD caused by HiAlc Kpn. IMPORTANCE HiAlc Kpn can use glucose to produce excess endogenous alcohol for promoting the development of NAFLD. Polymyxins are the last line of antibiotics and are commonly used to treat infections caused by carbapenem-resistant K. pneumoniae. In this study, we found that glucose increased bacterial resistance to polymyxins via increasing CPS and maintaining intracellular ATP; this increases the risk of failure to treat NAFLD caused by multidrug-resistant HiAlc Kpn infection. Further research revealed the important roles of glucose and the global regulator, CRP, in bacterial resistance and found that inhibiting CPS formation and decreasing intracellular ATP levels could effectively reverse glucose-induced polymyxins resistance. Our work reveals that glucose and the regulatory factor CRP can affect the resistance of bacteria to polymyxins, laying a foundation for the treatment of infections caused by multidrug-resistant bacteria. |
| first_indexed | 2024-03-12T14:31:16Z |
| format | Article |
| id | doaj.art-5295b2abefae43e8bc5e9cccc5f683d5 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-12T14:31:16Z |
| publishDate | 2023-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-5295b2abefae43e8bc5e9cccc5f683d52023-08-17T13:04:14ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-08-0111410.1128/spectrum.00031-23Glucose Induces Resistance to Polymyxins in High-Alcohol-Producing Klebsiella pneumoniae via Increasing Capsular Polysaccharide and Maintaining Intracellular ATPZheng Fan0Tongtong Fu1Hongbo Liu2Zhoufei Li3Bing Du4Xiaohu Cui5Rui Zhang6Yanling Feng7Hanqing Zhao8Guanhua Xue9Jinghua Cui10Chao Yan11Lin Gan12Junxia Feng13Ziying Xu14Zihui Yu15Ziyan Tian16Zanbo Ding17Jinfeng Chen18Yujie Chen19Jing Yuan20Department of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaSchool of Pharmaceutical Sciences, Jilin University, Changchun, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaUniversity of Edinburgh, Edinburgh, United KingdomDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaABSTRACT 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 the main carbon source. The role of glucose in the response of HiAlc Kpn to environmental stresses such as antibiotics remains unclear. In this study, we found that glucose could enhance the resistance of HiAlc Kpn to polymyxins. First, glucose inhibited the expression of crp in HiAlc Kpn and promoted the increase of capsular polysaccharide (CPS), which promoted the drug resistance of HiAlc Kpn. Second, glucose maintained high ATP levels in HiAlc Kpn cells under the pressure of polymyxins, enhancing the resistance of the cells to the killing effect of antibiotics. Notably, the inhibition of CPS formation and the decrease of intracellular ATP levels could both effectively reverse glucose-induced polymyxins resistance. Our work demonstrated the mechanism by which glucose induces polymyxins resistance in HiAlc Kpn, thereby laying the foundation for developing effective treatments for NAFLD caused by HiAlc Kpn. IMPORTANCE HiAlc Kpn can use glucose to produce excess endogenous alcohol for promoting the development of NAFLD. Polymyxins are the last line of antibiotics and are commonly used to treat infections caused by carbapenem-resistant K. pneumoniae. In this study, we found that glucose increased bacterial resistance to polymyxins via increasing CPS and maintaining intracellular ATP; this increases the risk of failure to treat NAFLD caused by multidrug-resistant HiAlc Kpn infection. Further research revealed the important roles of glucose and the global regulator, CRP, in bacterial resistance and found that inhibiting CPS formation and decreasing intracellular ATP levels could effectively reverse glucose-induced polymyxins resistance. Our work reveals that glucose and the regulatory factor CRP can affect the resistance of bacteria to polymyxins, laying a foundation for the treatment of infections caused by multidrug-resistant bacteria.https://journals.asm.org/doi/10.1128/spectrum.00031-23HiAlc KpnresistancepolymyxinscrpATPHiAlc Kpn |
| spellingShingle | 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 Glucose Induces Resistance to Polymyxins in High-Alcohol-Producing Klebsiella pneumoniae via Increasing Capsular Polysaccharide and Maintaining Intracellular ATP Microbiology Spectrum HiAlc Kpn resistance polymyxins crp ATP HiAlc Kpn |
| title | Glucose Induces Resistance to Polymyxins in High-Alcohol-Producing Klebsiella pneumoniae via Increasing Capsular Polysaccharide and Maintaining Intracellular ATP |
| title_full | Glucose Induces Resistance to Polymyxins in High-Alcohol-Producing Klebsiella pneumoniae via Increasing Capsular Polysaccharide and Maintaining Intracellular ATP |
| title_fullStr | Glucose Induces Resistance to Polymyxins in High-Alcohol-Producing Klebsiella pneumoniae via Increasing Capsular Polysaccharide and Maintaining Intracellular ATP |
| title_full_unstemmed | Glucose Induces Resistance to Polymyxins in High-Alcohol-Producing Klebsiella pneumoniae via Increasing Capsular Polysaccharide and Maintaining Intracellular ATP |
| title_short | Glucose Induces Resistance to Polymyxins in High-Alcohol-Producing Klebsiella pneumoniae via Increasing Capsular Polysaccharide and Maintaining Intracellular ATP |
| title_sort | glucose induces resistance to polymyxins in high alcohol producing klebsiella pneumoniae via increasing capsular polysaccharide and maintaining intracellular atp |
| topic | HiAlc Kpn resistance polymyxins crp ATP HiAlc Kpn |
| url | https://journals.asm.org/doi/10.1128/spectrum.00031-23 |
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