Identification of a Toxin–Antitoxin System That Contributes to Persister Formation by Reducing NAD in <i>Pseudomonas aeruginosa</i>
Bacterial persisters are slow-growing or dormant cells that are highly tolerant to bactericidal antibiotics and contribute to recalcitrant and chronic infections. Toxin/antitoxin (TA) systems play important roles in controlling persister formation. Here, we examined the roles of seven predicted type...
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MDPI AG
2021-04-01
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| Series: | Microorganisms |
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| author | Jingyi Zhou Shouyi Li Haozhou Li Yongxin Jin Fang Bai Zhihui Cheng Weihui Wu |
| author_facet | Jingyi Zhou Shouyi Li Haozhou Li Yongxin Jin Fang Bai Zhihui Cheng Weihui Wu |
| author_sort | Jingyi Zhou |
| collection | DOAJ |
| description | Bacterial persisters are slow-growing or dormant cells that are highly tolerant to bactericidal antibiotics and contribute to recalcitrant and chronic infections. Toxin/antitoxin (TA) systems play important roles in controlling persister formation. Here, we examined the roles of seven predicted type II TA systems in the persister formation of a <i>Pseudomonas aeruginosa</i> wild-type strain PA14. Overexpression of a toxin gene <i>PA14_51010</i> or deletion of the cognate antitoxin gene <i>PA14_51020</i> increased the bacterial tolerance to antibiotics. Co-overexpression of <i>PA14_51010</i> and <i>PA14_51020</i> or simultaneous deletion of the two genes resulted in a wild-type level survival rate following antibiotic treatment. The two genes were located in the same operon that was repressed by PA14_51020. We further demonstrated the interaction between PA14_51010 and PA14_51020. Sequence analysis revealed that PA14_51010 contained a conserved RES domain. Overexpression of <i>PA14_51010</i> reduced the intracellular level of nicotinamide adenine dinucleotide (NAD<sup>+</sup>). Mutation of the RES domain abolished the abilities of PA14_51010 in reducing NAD<sup>+</sup> level and promoting persister formation. In addition, overproduction of NAD<sup>+</sup> by mutation in an <i>nrt</i>R gene counteracted the effect of <i>PA14_51010</i> overexpression in promoting persister formation. In combination, our results reveal a novel TA system that contributes to persister formation through reducing the intracellular NAD<sup>+</sup> level in <i>P. aeruginosa</i>. |
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| last_indexed | 2024-03-10T12:38:21Z |
| publishDate | 2021-04-01 |
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| series | Microorganisms |
| spelling | doaj.art-19886695564441af8a0daa73e6d449432023-11-21T14:04:45ZengMDPI AGMicroorganisms2076-26072021-04-019475310.3390/microorganisms9040753Identification of a Toxin–Antitoxin System That Contributes to Persister Formation by Reducing NAD in <i>Pseudomonas aeruginosa</i>Jingyi Zhou0Shouyi Li1Haozhou Li2Yongxin Jin3Fang Bai4Zhihui Cheng5Weihui Wu6State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, ChinaState Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, ChinaState Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, ChinaState Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, ChinaState Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, ChinaState Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, ChinaState Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, ChinaBacterial persisters are slow-growing or dormant cells that are highly tolerant to bactericidal antibiotics and contribute to recalcitrant and chronic infections. Toxin/antitoxin (TA) systems play important roles in controlling persister formation. Here, we examined the roles of seven predicted type II TA systems in the persister formation of a <i>Pseudomonas aeruginosa</i> wild-type strain PA14. Overexpression of a toxin gene <i>PA14_51010</i> or deletion of the cognate antitoxin gene <i>PA14_51020</i> increased the bacterial tolerance to antibiotics. Co-overexpression of <i>PA14_51010</i> and <i>PA14_51020</i> or simultaneous deletion of the two genes resulted in a wild-type level survival rate following antibiotic treatment. The two genes were located in the same operon that was repressed by PA14_51020. We further demonstrated the interaction between PA14_51010 and PA14_51020. Sequence analysis revealed that PA14_51010 contained a conserved RES domain. Overexpression of <i>PA14_51010</i> reduced the intracellular level of nicotinamide adenine dinucleotide (NAD<sup>+</sup>). Mutation of the RES domain abolished the abilities of PA14_51010 in reducing NAD<sup>+</sup> level and promoting persister formation. In addition, overproduction of NAD<sup>+</sup> by mutation in an <i>nrt</i>R gene counteracted the effect of <i>PA14_51010</i> overexpression in promoting persister formation. In combination, our results reveal a novel TA system that contributes to persister formation through reducing the intracellular NAD<sup>+</sup> level in <i>P. aeruginosa</i>.https://www.mdpi.com/2076-2607/9/4/753<i>Pseudomonas aeruginosa</i>persistertoxin/antitoxin system |
| spellingShingle | Jingyi Zhou Shouyi Li Haozhou Li Yongxin Jin Fang Bai Zhihui Cheng Weihui Wu Identification of a Toxin–Antitoxin System That Contributes to Persister Formation by Reducing NAD in <i>Pseudomonas aeruginosa</i> Microorganisms <i>Pseudomonas aeruginosa</i> persister toxin/antitoxin system |
| title | Identification of a Toxin–Antitoxin System That Contributes to Persister Formation by Reducing NAD in <i>Pseudomonas aeruginosa</i> |
| title_full | Identification of a Toxin–Antitoxin System That Contributes to Persister Formation by Reducing NAD in <i>Pseudomonas aeruginosa</i> |
| title_fullStr | Identification of a Toxin–Antitoxin System That Contributes to Persister Formation by Reducing NAD in <i>Pseudomonas aeruginosa</i> |
| title_full_unstemmed | Identification of a Toxin–Antitoxin System That Contributes to Persister Formation by Reducing NAD in <i>Pseudomonas aeruginosa</i> |
| title_short | Identification of a Toxin–Antitoxin System That Contributes to Persister Formation by Reducing NAD in <i>Pseudomonas aeruginosa</i> |
| title_sort | identification of a toxin antitoxin system that contributes to persister formation by reducing nad in i pseudomonas aeruginosa i |
| topic | <i>Pseudomonas aeruginosa</i> persister toxin/antitoxin system |
| url | https://www.mdpi.com/2076-2607/9/4/753 |
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