The Mechanism of Tigecycline Resistance in <i>Acinetobacter baumannii</i> Revealed by Proteomic and Genomic Analysis
The mechanism of tigecycline resistance in <i>A. baumannii</i> remains largely unclear. In this study, we selected a tigecycline-resistant and a tigecycline-susceptible strain from a tigecycline-susceptible and a resistant strain, respectively. Proteomic and genomic analyses were perform...
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/10/8652 |
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| author | Cunwei Liu Lei Wang Ping Wang Di Xiao Qinghua Zou |
| author_facet | Cunwei Liu Lei Wang Ping Wang Di Xiao Qinghua Zou |
| author_sort | Cunwei Liu |
| collection | DOAJ |
| description | The mechanism of tigecycline resistance in <i>A. baumannii</i> remains largely unclear. In this study, we selected a tigecycline-resistant and a tigecycline-susceptible strain from a tigecycline-susceptible and a resistant strain, respectively. Proteomic and genomic analyses were performed to elucidate the variations associated with tigecycline resistance. Our study showed proteins associated with efflux pump, biofilm formation, iron acquisition, stress response, and metabolic ability are upregulated in tigecycline resistant strains, and efflux pump should be the key mechanism for tigecycline resistance. By genomic analysis, we found several changes in the genome that can explain the increased level of efflux pump, including the loss of the global negative regulator <i>hns</i> in the plasmid and the disruption of the <i>hns</i> gene and <i>acrR</i> gene on the chromosome by the insertion of IS5. Collectively, we not only revealed the phenomenon that the efflux pump is mainly responsible for tigecycline resistance, but also highlighted the mechanism at the genomic level, which will help in understanding the resistance mechanism in detail and provide clues for the treatment of clinical multiple drug-resistant <i>A. baumannii</i>. |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:40:45Z |
| publishDate | 2023-05-01 |
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| spelling | doaj.art-9928c552177d47a6862da55c1e16c8062023-11-18T01:39:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410865210.3390/ijms24108652The Mechanism of Tigecycline Resistance in <i>Acinetobacter baumannii</i> Revealed by Proteomic and Genomic AnalysisCunwei Liu0Lei Wang1Ping Wang2Di Xiao3Qinghua Zou4Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaState Key Laboratory of Communicable Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, ChinaDepartment of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaState Key Laboratory of Communicable Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, ChinaDepartment of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaThe mechanism of tigecycline resistance in <i>A. baumannii</i> remains largely unclear. In this study, we selected a tigecycline-resistant and a tigecycline-susceptible strain from a tigecycline-susceptible and a resistant strain, respectively. Proteomic and genomic analyses were performed to elucidate the variations associated with tigecycline resistance. Our study showed proteins associated with efflux pump, biofilm formation, iron acquisition, stress response, and metabolic ability are upregulated in tigecycline resistant strains, and efflux pump should be the key mechanism for tigecycline resistance. By genomic analysis, we found several changes in the genome that can explain the increased level of efflux pump, including the loss of the global negative regulator <i>hns</i> in the plasmid and the disruption of the <i>hns</i> gene and <i>acrR</i> gene on the chromosome by the insertion of IS5. Collectively, we not only revealed the phenomenon that the efflux pump is mainly responsible for tigecycline resistance, but also highlighted the mechanism at the genomic level, which will help in understanding the resistance mechanism in detail and provide clues for the treatment of clinical multiple drug-resistant <i>A. baumannii</i>.https://www.mdpi.com/1422-0067/24/10/8652<i>Acinetobacter baumannii</i>tigecycline resistanceproteomewhole genome sequencinginsertion sequence |
| spellingShingle | Cunwei Liu Lei Wang Ping Wang Di Xiao Qinghua Zou The Mechanism of Tigecycline Resistance in <i>Acinetobacter baumannii</i> Revealed by Proteomic and Genomic Analysis International Journal of Molecular Sciences <i>Acinetobacter baumannii</i> tigecycline resistance proteome whole genome sequencing insertion sequence |
| title | The Mechanism of Tigecycline Resistance in <i>Acinetobacter baumannii</i> Revealed by Proteomic and Genomic Analysis |
| title_full | The Mechanism of Tigecycline Resistance in <i>Acinetobacter baumannii</i> Revealed by Proteomic and Genomic Analysis |
| title_fullStr | The Mechanism of Tigecycline Resistance in <i>Acinetobacter baumannii</i> Revealed by Proteomic and Genomic Analysis |
| title_full_unstemmed | The Mechanism of Tigecycline Resistance in <i>Acinetobacter baumannii</i> Revealed by Proteomic and Genomic Analysis |
| title_short | The Mechanism of Tigecycline Resistance in <i>Acinetobacter baumannii</i> Revealed by Proteomic and Genomic Analysis |
| title_sort | mechanism of tigecycline resistance in i acinetobacter baumannii i revealed by proteomic and genomic analysis |
| topic | <i>Acinetobacter baumannii</i> tigecycline resistance proteome whole genome sequencing insertion sequence |
| url | https://www.mdpi.com/1422-0067/24/10/8652 |
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