Disruption of sulfur transferase complex increases bacterial intramacrophage persistence.
Bacterial persisters contribute significantly to clinical treatment failure and relapse. These cells could resist antibiotic treatment via transient phenotypic and gene expression alterations. We conducted a high-throughput screening of Salmonella Typhimurium transposon mutants to identify key genes...
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| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1013136 |
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| _version_ | 1849714530269003776 |
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| author | Huang Tang Zuoqiang Wang Congcong Li Jingchen Yu Wanqiu Huang Tao Zhou Chuanzhen Zhang Bingjie Wen Chengyue Wang Xiaocen Zhu Danni Wang Jing Tao Jie Lu Jinjing Ni Yu-Feng Yao |
| author_facet | Huang Tang Zuoqiang Wang Congcong Li Jingchen Yu Wanqiu Huang Tao Zhou Chuanzhen Zhang Bingjie Wen Chengyue Wang Xiaocen Zhu Danni Wang Jing Tao Jie Lu Jinjing Ni Yu-Feng Yao |
| author_sort | Huang Tang |
| collection | DOAJ |
| description | Bacterial persisters contribute significantly to clinical treatment failure and relapse. These cells could resist antibiotic treatment via transient phenotypic and gene expression alterations. We conducted a high-throughput screening of Salmonella Typhimurium transposon mutants to identify key genes for intramacrophage antibiotic persistence. The results show that a sulfur transferase complex encoded by yheM, yheL, yheN, trmU and yhhP are involved in bacterial intramacrophage antibiotic persistence. Salmonella could persist in macrophages by downregulating the expression of the sulfur transferase complex during exposure to high concentrations of antibiotics, and even in a persistent infection mouse model. Mechanistically, deletion of yheM increases reactive nitrogen species (RNS) in the exponential phase, which inhibits bacterial respiration and ATP generation. In contrast, absence of yheM promotes persister formation by elevating (p)ppGpp levels in the stationary phase. Taken together, our data demonstrate that bacteria use the sulfur transferase to coordinate intramacrophage replication and persistence for adaptation to various environmental stresses. These findings reveal the role of the sulfur transferase complex in bacterial intramacrophage persistence and provide a promising target for antibacterial infection therapy. |
| format | Article |
| id | doaj-art-628aa24d45884ee4adab35ea7e58d466 |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-628aa24d45884ee4adab35ea7e58d4662025-08-20T03:13:40ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-05-01215e101313610.1371/journal.ppat.1013136Disruption of sulfur transferase complex increases bacterial intramacrophage persistence.Huang TangZuoqiang WangCongcong LiJingchen YuWanqiu HuangTao ZhouChuanzhen ZhangBingjie WenChengyue WangXiaocen ZhuDanni WangJing TaoJie LuJinjing NiYu-Feng YaoBacterial persisters contribute significantly to clinical treatment failure and relapse. These cells could resist antibiotic treatment via transient phenotypic and gene expression alterations. We conducted a high-throughput screening of Salmonella Typhimurium transposon mutants to identify key genes for intramacrophage antibiotic persistence. The results show that a sulfur transferase complex encoded by yheM, yheL, yheN, trmU and yhhP are involved in bacterial intramacrophage antibiotic persistence. Salmonella could persist in macrophages by downregulating the expression of the sulfur transferase complex during exposure to high concentrations of antibiotics, and even in a persistent infection mouse model. Mechanistically, deletion of yheM increases reactive nitrogen species (RNS) in the exponential phase, which inhibits bacterial respiration and ATP generation. In contrast, absence of yheM promotes persister formation by elevating (p)ppGpp levels in the stationary phase. Taken together, our data demonstrate that bacteria use the sulfur transferase to coordinate intramacrophage replication and persistence for adaptation to various environmental stresses. These findings reveal the role of the sulfur transferase complex in bacterial intramacrophage persistence and provide a promising target for antibacterial infection therapy.https://doi.org/10.1371/journal.ppat.1013136 |
| spellingShingle | Huang Tang Zuoqiang Wang Congcong Li Jingchen Yu Wanqiu Huang Tao Zhou Chuanzhen Zhang Bingjie Wen Chengyue Wang Xiaocen Zhu Danni Wang Jing Tao Jie Lu Jinjing Ni Yu-Feng Yao Disruption of sulfur transferase complex increases bacterial intramacrophage persistence. PLoS Pathogens |
| title | Disruption of sulfur transferase complex increases bacterial intramacrophage persistence. |
| title_full | Disruption of sulfur transferase complex increases bacterial intramacrophage persistence. |
| title_fullStr | Disruption of sulfur transferase complex increases bacterial intramacrophage persistence. |
| title_full_unstemmed | Disruption of sulfur transferase complex increases bacterial intramacrophage persistence. |
| title_short | Disruption of sulfur transferase complex increases bacterial intramacrophage persistence. |
| title_sort | disruption of sulfur transferase complex increases bacterial intramacrophage persistence |
| url | https://doi.org/10.1371/journal.ppat.1013136 |
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