The fatty acid synthesis gene fabY affects lipopolysaccharide synthesis and colistin susceptibility in Pseudomonas aeruginosa
ABSTRACT Bacterial metabolism impacts susceptibility to antibiotics. Here, we found that mutation of the Pseudomonas aeruginosa fatty acid response regulator gene pvrA decreases bacterial susceptibility to colistin. The fatty acid synthesis gene fabY is upregulated in the pvrA mutant. Deletion of fa...
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American Society for Microbiology
2025-08-01
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| Series: | Microbiology Spectrum |
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| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.01339-25 |
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| author | Dandan Zhou Xiaoya Wei Yongxin Jin Zhihui Cheng Shouguang Jin Un-Hwan Ha Xiaolei Pan Weihui Wu |
| author_facet | Dandan Zhou Xiaoya Wei Yongxin Jin Zhihui Cheng Shouguang Jin Un-Hwan Ha Xiaolei Pan Weihui Wu |
| author_sort | Dandan Zhou |
| collection | DOAJ |
| description | ABSTRACT Bacterial metabolism impacts susceptibility to antibiotics. Here, we found that mutation of the Pseudomonas aeruginosa fatty acid response regulator gene pvrA decreases bacterial susceptibility to colistin. The fatty acid synthesis gene fabY is upregulated in the pvrA mutant. Deletion of fabY in either the pvrA mutant or wild-type strain increases bacterial susceptibility to colistin. Further investigation reveals that the mutation of fabY enhances lipopolysaccharide production, thereby increasing the surface binding of colistin and bacterial susceptibility.IMPORTANCEThis project explored the influence of bacterial metabolism on antibiotic sensitivity and found a new mechanism to make Pseudomonas aeruginosa sensitive to colistin by interfering with fatty acid synthesis. In this study, it was observed that the mutation of the fatty acid metabolism regulation gene pvrA in P. aeruginosa reduced the susceptibility of bacteria to colistin. It was also found that the fatty acid synthesis gene fabY was up-regulated in the pvrA mutant. Further investigation showed that the fabY mutation enhanced the production of lipopolysaccharide and increased the surface binding and bacterial sensitivity of colistin. This study shows that the therapeutic effect can be enhanced by developing fatty acid synthesis inhibitors combined with polymyxin, and it provides a new target for antibiotic treatment. |
| format | Article |
| id | doaj-art-1759b42df9e94159a8b0eea7f21d2dcd |
| institution | DOAJ |
| issn | 2165-0497 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj-art-1759b42df9e94159a8b0eea7f21d2dcd2025-08-20T02:56:24ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-08-0113810.1128/spectrum.01339-25The fatty acid synthesis gene fabY affects lipopolysaccharide synthesis and colistin susceptibility in Pseudomonas aeruginosaDandan Zhou0Xiaoya Wei1Yongxin Jin2Zhihui Cheng3Shouguang Jin4Un-Hwan Ha5Xiaolei Pan6Weihui Wu7State 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, 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, 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, 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, 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, ChinaDepartment of Biotechnology and Bioinformatics, Korea University, Sejong, South KoreaDepartment of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 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, ChinaABSTRACT Bacterial metabolism impacts susceptibility to antibiotics. Here, we found that mutation of the Pseudomonas aeruginosa fatty acid response regulator gene pvrA decreases bacterial susceptibility to colistin. The fatty acid synthesis gene fabY is upregulated in the pvrA mutant. Deletion of fabY in either the pvrA mutant or wild-type strain increases bacterial susceptibility to colistin. Further investigation reveals that the mutation of fabY enhances lipopolysaccharide production, thereby increasing the surface binding of colistin and bacterial susceptibility.IMPORTANCEThis project explored the influence of bacterial metabolism on antibiotic sensitivity and found a new mechanism to make Pseudomonas aeruginosa sensitive to colistin by interfering with fatty acid synthesis. In this study, it was observed that the mutation of the fatty acid metabolism regulation gene pvrA in P. aeruginosa reduced the susceptibility of bacteria to colistin. It was also found that the fatty acid synthesis gene fabY was up-regulated in the pvrA mutant. Further investigation showed that the fabY mutation enhanced the production of lipopolysaccharide and increased the surface binding and bacterial sensitivity of colistin. This study shows that the therapeutic effect can be enhanced by developing fatty acid synthesis inhibitors combined with polymyxin, and it provides a new target for antibiotic treatment.https://journals.asm.org/doi/10.1128/spectrum.01339-25Pseudomonas aeruginosafatty acidlipopolysaccharidecolistinfabY |
| spellingShingle | Dandan Zhou Xiaoya Wei Yongxin Jin Zhihui Cheng Shouguang Jin Un-Hwan Ha Xiaolei Pan Weihui Wu The fatty acid synthesis gene fabY affects lipopolysaccharide synthesis and colistin susceptibility in Pseudomonas aeruginosa Microbiology Spectrum Pseudomonas aeruginosa fatty acid lipopolysaccharide colistin fabY |
| title | The fatty acid synthesis gene fabY affects lipopolysaccharide synthesis and colistin susceptibility in Pseudomonas aeruginosa |
| title_full | The fatty acid synthesis gene fabY affects lipopolysaccharide synthesis and colistin susceptibility in Pseudomonas aeruginosa |
| title_fullStr | The fatty acid synthesis gene fabY affects lipopolysaccharide synthesis and colistin susceptibility in Pseudomonas aeruginosa |
| title_full_unstemmed | The fatty acid synthesis gene fabY affects lipopolysaccharide synthesis and colistin susceptibility in Pseudomonas aeruginosa |
| title_short | The fatty acid synthesis gene fabY affects lipopolysaccharide synthesis and colistin susceptibility in Pseudomonas aeruginosa |
| title_sort | fatty acid synthesis gene faby affects lipopolysaccharide synthesis and colistin susceptibility in pseudomonas aeruginosa |
| topic | Pseudomonas aeruginosa fatty acid lipopolysaccharide colistin fabY |
| url | https://journals.asm.org/doi/10.1128/spectrum.01339-25 |
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