Histone-Like Nucleoid Structuring Protein Modulates the Fitness of tet(X4)-Bearing IncX1 Plasmids in Gram-Negative Bacteria
The emergence of plasmid-mediated tigecycline resistance gene tet(X4) poses a challenging threat to public health. Based on the analysis of tet(X4)-positive plasmids in the NCBI database, we found that the IncX1-type plasmid is one of the most common vectors for spreading tet(X4) gene, but the mecha...
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| Format: | Article |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2021.763288/full |
| _version_ | 1819025594081345536 |
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| author | Wenhui Cai Feifei Tang Lijie Jiang Ruichao Li Ruichao Li Ruichao Li Ruichao Li Zhiqiang Wang Zhiqiang Wang Zhiqiang Wang Yuan Liu Yuan Liu Yuan Liu Yuan Liu |
| author_facet | Wenhui Cai Feifei Tang Lijie Jiang Ruichao Li Ruichao Li Ruichao Li Ruichao Li Zhiqiang Wang Zhiqiang Wang Zhiqiang Wang Yuan Liu Yuan Liu Yuan Liu Yuan Liu |
| author_sort | Wenhui Cai |
| collection | DOAJ |
| description | The emergence of plasmid-mediated tigecycline resistance gene tet(X4) poses a challenging threat to public health. Based on the analysis of tet(X4)-positive plasmids in the NCBI database, we found that the IncX1-type plasmid is one of the most common vectors for spreading tet(X4) gene, but the mechanisms by which these plasmids adapt to host bacteria and maintain the persistence of antibiotic resistance genes (ARGs) remain unclear. Herein, we investigated the underlying mechanisms of how host bacteria modulate the fitness cost of IncX1 plasmids carrying tet(X4) gene. Interestingly, we found that the tet(X4)-bearing IncX1 plasmids encoding H-NS protein imposed low or no fitness cost in Escherichia coli and Klebsiella pneumoniae; instead, they partially promoted the virulence and biofilm formation in host bacteria. Regression analysis revealed that the expression of hns gene in plasmids was positively linked to the relative fitness of host bacteria. Furthermore, when pCE2::hns was introduced, the fitness of tet(X4)-positive IncX1 plasmid pRF55-1 without hns gene was significantly improved, indicating that hns mediates the improvement of fitness. Finally, we showed that the expression of hns gene is negatively correlated with the expression of tet(X4) gene, suggesting that the regulatory effect of H-NS on adaptability may be attributed to its inhibitory effect on the expression of ARGs. Together, our findings suggest the important role of plasmid-encoded H-NS protein in modulating the fitness of tet(X4)-bearing IncX1 plasmids, which shed new insight into the dissemination of tet(X4) gene in a biological environment. |
| first_indexed | 2024-12-21T05:13:09Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-21T05:13:09Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-f5d9c7fbe4d84bdc8c7a76b5d0983d6b2022-12-21T19:15:00ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-11-011210.3389/fmicb.2021.763288763288Histone-Like Nucleoid Structuring Protein Modulates the Fitness of tet(X4)-Bearing IncX1 Plasmids in Gram-Negative BacteriaWenhui Cai0Feifei Tang1Lijie Jiang2Ruichao Li3Ruichao Li4Ruichao Li5Ruichao Li6Zhiqiang Wang7Zhiqiang Wang8Zhiqiang Wang9Yuan Liu10Yuan Liu11Yuan Liu12Yuan Liu13College of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaJiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, ChinaInstitute of Comparative Medicine, Yangzhou University, Yangzhou, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaJiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaJiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, ChinaInstitute of Comparative Medicine, Yangzhou University, Yangzhou, ChinaThe emergence of plasmid-mediated tigecycline resistance gene tet(X4) poses a challenging threat to public health. Based on the analysis of tet(X4)-positive plasmids in the NCBI database, we found that the IncX1-type plasmid is one of the most common vectors for spreading tet(X4) gene, but the mechanisms by which these plasmids adapt to host bacteria and maintain the persistence of antibiotic resistance genes (ARGs) remain unclear. Herein, we investigated the underlying mechanisms of how host bacteria modulate the fitness cost of IncX1 plasmids carrying tet(X4) gene. Interestingly, we found that the tet(X4)-bearing IncX1 plasmids encoding H-NS protein imposed low or no fitness cost in Escherichia coli and Klebsiella pneumoniae; instead, they partially promoted the virulence and biofilm formation in host bacteria. Regression analysis revealed that the expression of hns gene in plasmids was positively linked to the relative fitness of host bacteria. Furthermore, when pCE2::hns was introduced, the fitness of tet(X4)-positive IncX1 plasmid pRF55-1 without hns gene was significantly improved, indicating that hns mediates the improvement of fitness. Finally, we showed that the expression of hns gene is negatively correlated with the expression of tet(X4) gene, suggesting that the regulatory effect of H-NS on adaptability may be attributed to its inhibitory effect on the expression of ARGs. Together, our findings suggest the important role of plasmid-encoded H-NS protein in modulating the fitness of tet(X4)-bearing IncX1 plasmids, which shed new insight into the dissemination of tet(X4) gene in a biological environment.https://www.frontiersin.org/articles/10.3389/fmicb.2021.763288/fullH-NS proteinfitnesstet(X4)IncX1 plasmidsGram-negative bacteria (GNB) |
| spellingShingle | Wenhui Cai Feifei Tang Lijie Jiang Ruichao Li Ruichao Li Ruichao Li Ruichao Li Zhiqiang Wang Zhiqiang Wang Zhiqiang Wang Yuan Liu Yuan Liu Yuan Liu Yuan Liu Histone-Like Nucleoid Structuring Protein Modulates the Fitness of tet(X4)-Bearing IncX1 Plasmids in Gram-Negative Bacteria Frontiers in Microbiology H-NS protein fitness tet(X4) IncX1 plasmids Gram-negative bacteria (GNB) |
| title | Histone-Like Nucleoid Structuring Protein Modulates the Fitness of tet(X4)-Bearing IncX1 Plasmids in Gram-Negative Bacteria |
| title_full | Histone-Like Nucleoid Structuring Protein Modulates the Fitness of tet(X4)-Bearing IncX1 Plasmids in Gram-Negative Bacteria |
| title_fullStr | Histone-Like Nucleoid Structuring Protein Modulates the Fitness of tet(X4)-Bearing IncX1 Plasmids in Gram-Negative Bacteria |
| title_full_unstemmed | Histone-Like Nucleoid Structuring Protein Modulates the Fitness of tet(X4)-Bearing IncX1 Plasmids in Gram-Negative Bacteria |
| title_short | Histone-Like Nucleoid Structuring Protein Modulates the Fitness of tet(X4)-Bearing IncX1 Plasmids in Gram-Negative Bacteria |
| title_sort | histone like nucleoid structuring protein modulates the fitness of tet x4 bearing incx1 plasmids in gram negative bacteria |
| topic | H-NS protein fitness tet(X4) IncX1 plasmids Gram-negative bacteria (GNB) |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2021.763288/full |
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