MomL inhibits bacterial antibiotic resistance through the starvation stringent response pathway
Abstract Antibiotic resistance in gram‐negative pathogens has become one of the most serious global public health threats. The role of the N‐acyl homoserine lactone (AHL)‐mediated signaling pathway, which is widespread in gram‐negative bacteria, in the bacterial resistance process should be studied...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-12-01
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| Series: | mLife |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mlf2.12016 |
| _version_ | 1811170916968693760 |
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| author | Qin Dou Jin Yuan Rilei Yu Jiahui Yang Jiayi Wang Yuxiang Zhu Jing Zhong Hongan Long Zhiqing Liu Xianghong Wang Yuying Li Yichen Xiao Jiazhen Liang Xiao‐Hua Zhang Yan Wang |
| author_facet | Qin Dou Jin Yuan Rilei Yu Jiahui Yang Jiayi Wang Yuxiang Zhu Jing Zhong Hongan Long Zhiqing Liu Xianghong Wang Yuying Li Yichen Xiao Jiazhen Liang Xiao‐Hua Zhang Yan Wang |
| author_sort | Qin Dou |
| collection | DOAJ |
| description | Abstract Antibiotic resistance in gram‐negative pathogens has become one of the most serious global public health threats. The role of the N‐acyl homoserine lactone (AHL)‐mediated signaling pathway, which is widespread in gram‐negative bacteria, in the bacterial resistance process should be studied in depth. Here, we report a degrading enzyme of AHLs, MomL, that inhibits the antibiotic resistance of Pseudomonas aeruginosa through a novel mechanism. The MomL‐mediated reactivation of kanamycin is highly associated with the relA‐mediated starvation stringent response. The degradation of AHLs by MomL results in the inability of LasR to activate relA, which, in turn, stops the activation of downstream rpoS. Further results show that rpoS directly regulates the type VI secretion system H2‐T6SS. Under MomL treatment, inactivated RpoS fails to regulate H2‐T6SS; therefore, the expression of effector phospholipase A is reduced, and the adaptability of bacteria to antibiotics is weakened. MomL in combination with kanamycin is effective against a wide range of gram‐negative pathogenic bacteria. Therefore, this study reports a MomL‐antibiotic treatment strategy on antibiotic‐resistant bacteria and reveals its mechanism of action. |
| first_indexed | 2024-04-10T17:04:41Z |
| format | Article |
| id | doaj.art-ff82ec9ecabe4e43864ee5e018bfe6ab |
| institution | Directory Open Access Journal |
| issn | 2770-100X |
| language | English |
| last_indexed | 2024-04-10T17:04:41Z |
| publishDate | 2022-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | mLife |
| spelling | doaj.art-ff82ec9ecabe4e43864ee5e018bfe6ab2023-02-06T07:06:42ZengWileymLife2770-100X2022-12-011442844210.1002/mlf2.12016MomL inhibits bacterial antibiotic resistance through the starvation stringent response pathwayQin Dou0Jin Yuan1Rilei Yu2Jiahui Yang3Jiayi Wang4Yuxiang Zhu5Jing Zhong6Hongan Long7Zhiqing Liu8Xianghong Wang9Yuying Li10Yichen Xiao11Jiazhen Liang12Xiao‐Hua Zhang13Yan Wang14College of Marine Life Sciences, and Institute of Evolution & Marine Biodiversity Ocean University of China Qingdao ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center Sun Yat‐Sen University Guangzhou ChinaKey Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy Ocean University of China Qingdao ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center Sun Yat‐Sen University Guangzhou ChinaCollege of Marine Life Sciences, and Institute of Evolution & Marine Biodiversity Ocean University of China Qingdao ChinaCollege of Marine Life Sciences, and Institute of Evolution & Marine Biodiversity Ocean University of China Qingdao ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center Sun Yat‐Sen University Guangzhou ChinaCollege of Marine Life Sciences, and Institute of Evolution & Marine Biodiversity Ocean University of China Qingdao ChinaCollege of Marine Life Sciences, and Institute of Evolution & Marine Biodiversity Ocean University of China Qingdao ChinaCollege of Marine Life Sciences, and Institute of Evolution & Marine Biodiversity Ocean University of China Qingdao ChinaCollege of Marine Life Sciences, and Institute of Evolution & Marine Biodiversity Ocean University of China Qingdao ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center Sun Yat‐Sen University Guangzhou ChinaKey Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy Ocean University of China Qingdao ChinaCollege of Marine Life Sciences, and Institute of Evolution & Marine Biodiversity Ocean University of China Qingdao ChinaCollege of Marine Life Sciences, and Institute of Evolution & Marine Biodiversity Ocean University of China Qingdao ChinaAbstract Antibiotic resistance in gram‐negative pathogens has become one of the most serious global public health threats. The role of the N‐acyl homoserine lactone (AHL)‐mediated signaling pathway, which is widespread in gram‐negative bacteria, in the bacterial resistance process should be studied in depth. Here, we report a degrading enzyme of AHLs, MomL, that inhibits the antibiotic resistance of Pseudomonas aeruginosa through a novel mechanism. The MomL‐mediated reactivation of kanamycin is highly associated with the relA‐mediated starvation stringent response. The degradation of AHLs by MomL results in the inability of LasR to activate relA, which, in turn, stops the activation of downstream rpoS. Further results show that rpoS directly regulates the type VI secretion system H2‐T6SS. Under MomL treatment, inactivated RpoS fails to regulate H2‐T6SS; therefore, the expression of effector phospholipase A is reduced, and the adaptability of bacteria to antibiotics is weakened. MomL in combination with kanamycin is effective against a wide range of gram‐negative pathogenic bacteria. Therefore, this study reports a MomL‐antibiotic treatment strategy on antibiotic‐resistant bacteria and reveals its mechanism of action.https://doi.org/10.1002/mlf2.12016AHLsantibiotic resistanceH2‐T6SSPseudomonas aeruginosastarvation stringent response |
| spellingShingle | Qin Dou Jin Yuan Rilei Yu Jiahui Yang Jiayi Wang Yuxiang Zhu Jing Zhong Hongan Long Zhiqing Liu Xianghong Wang Yuying Li Yichen Xiao Jiazhen Liang Xiao‐Hua Zhang Yan Wang MomL inhibits bacterial antibiotic resistance through the starvation stringent response pathway mLife AHLs antibiotic resistance H2‐T6SS Pseudomonas aeruginosa starvation stringent response |
| title | MomL inhibits bacterial antibiotic resistance through the starvation stringent response pathway |
| title_full | MomL inhibits bacterial antibiotic resistance through the starvation stringent response pathway |
| title_fullStr | MomL inhibits bacterial antibiotic resistance through the starvation stringent response pathway |
| title_full_unstemmed | MomL inhibits bacterial antibiotic resistance through the starvation stringent response pathway |
| title_short | MomL inhibits bacterial antibiotic resistance through the starvation stringent response pathway |
| title_sort | moml inhibits bacterial antibiotic resistance through the starvation stringent response pathway |
| topic | AHLs antibiotic resistance H2‐T6SS Pseudomonas aeruginosa starvation stringent response |
| url | https://doi.org/10.1002/mlf2.12016 |
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