Within-host evolution of a transcriptional regulator contributes to the establishment of chronic Pseudomonas aeruginosa infection
Summary: As an opportunistic pathogen, Pseudomonas aeruginosa can cause both acute and chronic infections that are notoriously difficult to treat. However, the mechanism underlying acute or chronic P. aeruginosa infection remains unclear. Here, we identify a mutation in a transcriptional regulator P...
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Elsevier
2025-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724015651 |
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| author | Ning Zhou Jingchen Yu Xujiao Liu Chengxi Li Huang Tang Lin Lyu Chengwei Wu Yana Chen Jian Zhang Jinjing Ni Danni Wang Jing Tao Wenjuan Wu Yu Zhang Yun Feng Yanjie Chao Jie Lu Ping He Yu-Feng Yao |
| author_facet | Ning Zhou Jingchen Yu Xujiao Liu Chengxi Li Huang Tang Lin Lyu Chengwei Wu Yana Chen Jian Zhang Jinjing Ni Danni Wang Jing Tao Wenjuan Wu Yu Zhang Yun Feng Yanjie Chao Jie Lu Ping He Yu-Feng Yao |
| author_sort | Ning Zhou |
| collection | DOAJ |
| description | Summary: As an opportunistic pathogen, Pseudomonas aeruginosa can cause both acute and chronic infections that are notoriously difficult to treat. However, the mechanism underlying acute or chronic P. aeruginosa infection remains unclear. Here, we identify a mutation in a transcriptional regulator PA5438 (named GavR). This mutation causes a 3-amino-acid absence in GavR and is strongly associated with chronic P. aeruginosa infection. Mechanistically, the deletion in GavR directly downregulates the transcription of the aceEF operon and leads to an accumulation of intracellular pyruvate, which can promote bacterial survival in neutrophils. Notably, P. aeruginosa with 9-bp-deleted or full-length gavR composes a mixed population in most patients with chronic or acute infections. Overall, the mutation in gavR attenuates P. aeruginosa virulence and enhances innate immune evasion by reprogramming pyruvate metabolism and the glyoxylate cycle. This work reveals a molecular mechanism of transition control from acute to chronic infection in P. aeruginosa. |
| format | Article |
| id | doaj-art-afbba7f12fae4b2ebf69e372ef1dd9d5 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-afbba7f12fae4b2ebf69e372ef1dd9d52025-01-18T05:04:27ZengElsevierCell Reports2211-12472025-01-01441115214Within-host evolution of a transcriptional regulator contributes to the establishment of chronic Pseudomonas aeruginosa infectionNing Zhou0Jingchen Yu1Xujiao Liu2Chengxi Li3Huang Tang4Lin Lyu5Chengwei Wu6Yana Chen7Jian Zhang8Jinjing Ni9Danni Wang10Jing Tao11Wenjuan Wu12Yu Zhang13Yun Feng14Yanjie Chao15Jie Lu16Ping He17Yu-Feng Yao18Laboratory of Bacterial Pathogenesis, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaLaboratory of Bacterial Pathogenesis, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaKey Laboratory of Synthetic Biology, Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, ChinaAnhui Key Laboratory of Infection and Immunity, Department of Microbiology and Parasitology, Bengbu Medical College, Bengbu, Anhui 233030, ChinaLaboratory of Bacterial Pathogenesis, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaLaboratory of Bacterial Pathogenesis, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaMedicinal Chemistry and Bioinformatics Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDepartment of Pediatrics, Anhui Provincial Hospital, The First Affiliated Hospital of USTC, Hefei, Anhui 230001, ChinaMedicinal Chemistry and Bioinformatics Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaLaboratory of Bacterial Pathogenesis, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaLaboratory of Bacterial Pathogenesis, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaLaboratory of Bacterial Pathogenesis, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDepartment of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, ChinaKey Laboratory of Synthetic Biology, Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, ChinaDepartment of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, ChinaShanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai 200031, ChinaDepartment of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Corresponding authorDepartment of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Corresponding authorLaboratory of Bacterial Pathogenesis, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; State Key Laboratory of Microbial Metabolism, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases (20dz2261100), Shanghai 200025, China; Corresponding authorSummary: As an opportunistic pathogen, Pseudomonas aeruginosa can cause both acute and chronic infections that are notoriously difficult to treat. However, the mechanism underlying acute or chronic P. aeruginosa infection remains unclear. Here, we identify a mutation in a transcriptional regulator PA5438 (named GavR). This mutation causes a 3-amino-acid absence in GavR and is strongly associated with chronic P. aeruginosa infection. Mechanistically, the deletion in GavR directly downregulates the transcription of the aceEF operon and leads to an accumulation of intracellular pyruvate, which can promote bacterial survival in neutrophils. Notably, P. aeruginosa with 9-bp-deleted or full-length gavR composes a mixed population in most patients with chronic or acute infections. Overall, the mutation in gavR attenuates P. aeruginosa virulence and enhances innate immune evasion by reprogramming pyruvate metabolism and the glyoxylate cycle. This work reveals a molecular mechanism of transition control from acute to chronic infection in P. aeruginosa.http://www.sciencedirect.com/science/article/pii/S2211124724015651CP: MicrobiologyCP: Metabolism |
| spellingShingle | Ning Zhou Jingchen Yu Xujiao Liu Chengxi Li Huang Tang Lin Lyu Chengwei Wu Yana Chen Jian Zhang Jinjing Ni Danni Wang Jing Tao Wenjuan Wu Yu Zhang Yun Feng Yanjie Chao Jie Lu Ping He Yu-Feng Yao Within-host evolution of a transcriptional regulator contributes to the establishment of chronic Pseudomonas aeruginosa infection Cell Reports CP: Microbiology CP: Metabolism |
| title | Within-host evolution of a transcriptional regulator contributes to the establishment of chronic Pseudomonas aeruginosa infection |
| title_full | Within-host evolution of a transcriptional regulator contributes to the establishment of chronic Pseudomonas aeruginosa infection |
| title_fullStr | Within-host evolution of a transcriptional regulator contributes to the establishment of chronic Pseudomonas aeruginosa infection |
| title_full_unstemmed | Within-host evolution of a transcriptional regulator contributes to the establishment of chronic Pseudomonas aeruginosa infection |
| title_short | Within-host evolution of a transcriptional regulator contributes to the establishment of chronic Pseudomonas aeruginosa infection |
| title_sort | within host evolution of a transcriptional regulator contributes to the establishment of chronic pseudomonas aeruginosa infection |
| topic | CP: Microbiology CP: Metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724015651 |
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