International journal of antimicrobial agents · 2026
L-Cycloserine, not d-Cycloserine, inhibits IscS-mediated iron-sulfur cluster biosynthesis in Escherichia coli.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhang Lihe, Li Yongjuan, Bao Yuhang, Feng Jie, Chen Runyu, Zhang Wenjing, Zhu Yixuan, Zhang Liwen, Zhang Yin, Liang Feng, Chen Huimin, Luo Xinhua, Tan Guoqiang, Wang Wu
Аннотация
OBJECTIVES: D-Cycloserine (DCS) is a broad-spectrum antibiotic used to treat drug-resistant tuberculosis, primarily by inhibiting pyridoxal 5'-phosphate (PLP)-dependent enzymes. Recent studies suggest that cycloserine may also target cysteine desulfurases involved in iron-sulfur (Fe-S) cluster biogenesis, but the underlying mechanism remains unclear. This study aims to elucidate the mechanistic details of how cycloserine affects Fe-S cluster assembly and to explore its potential against resistant strains.
METHODS: The effects of DCS and its enantiomer L-Cycloserine (LCS) on Fe-S cluster biosynthesis were investigated using Escherichia coli (E. coli) IscS as a model cysteine desulfurase. Enzyme activity assays were performed to assess inhibition. Liquid chromatography-mass spectrometry (LC-MS) was employed to analyze changes in the PLP cofactor bound to IscS. Antimicrobial efficacy was tested against the uropathogenic E. coli strain CFT073 and experimentally evolved DCS-resistant strains in synthetic human urine medium.
RESULTS: LCS, but not DCS, inhibited the cysteine desulfurase activity of IscS, leading to impaired Fe-S cluster biosynthesis. Specifically, LC-MS analysis revealed that LCS converts the PLP cofactor bound to IscS to pyridoxamine 5'-phosphate (PMP). Furthermore, LCS significantly suppressed the growth of uropathogenic E. coli CFT073 and retained effectiveness against DCS-resistant strains in synthetic human urine medium.
CONCLUSIONS: These findings demonstrate that LCS inhibits Fe-S cluster biosynthesis by targeting the cysteine desulfurase IscS through PLP-to-PMP conversion. The results highlight Fe-S cluster biogenesis as a potential antimicrobial target and suggest that LCS may serve as a promising therapeutic alternative for combating DCS-resistant bacterial infections.
METHODS: The effects of DCS and its enantiomer L-Cycloserine (LCS) on Fe-S cluster biosynthesis were investigated using Escherichia coli (E. coli) IscS as a model cysteine desulfurase. Enzyme activity assays were performed to assess inhibition. Liquid chromatography-mass spectrometry (LC-MS) was employed to analyze changes in the PLP cofactor bound to IscS. Antimicrobial efficacy was tested against the uropathogenic E. coli strain CFT073 and experimentally evolved DCS-resistant strains in synthetic human urine medium.
RESULTS: LCS, but not DCS, inhibited the cysteine desulfurase activity of IscS, leading to impaired Fe-S cluster biosynthesis. Specifically, LC-MS analysis revealed that LCS converts the PLP cofactor bound to IscS to pyridoxamine 5'-phosphate (PMP). Furthermore, LCS significantly suppressed the growth of uropathogenic E. coli CFT073 and retained effectiveness against DCS-resistant strains in synthetic human urine medium.
CONCLUSIONS: These findings demonstrate that LCS inhibits Fe-S cluster biosynthesis by targeting the cysteine desulfurase IscS through PLP-to-PMP conversion. The results highlight Fe-S cluster biogenesis as a potential antimicrobial target and suggest that LCS may serve as a promising therapeutic alternative for combating DCS-resistant bacterial infections.