Fitness Costs of Tigecycline Resistance in <i>Acinetobacter baumannii</i> and the Resistance Mechanism Revealed by a Transposon Mutation Library
<i>Acinetobacter baumannii</i> is one of the main pathogens causing nosocomial and community-acquired infections. Tigecycline is an important antibiotic for the treatment of multidrug-resistant <i>A. baumannii</i> infections, but strains resistant to tigecycline have also eme...
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MDPI AG
2022-10-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/10/1379 |
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| author | Ping Wang Hongou Wang Cunwei Liu Chengjie Feng Qinghui Lu Qinghua Zou |
| author_facet | Ping Wang Hongou Wang Cunwei Liu Chengjie Feng Qinghui Lu Qinghua Zou |
| author_sort | Ping Wang |
| collection | DOAJ |
| description | <i>Acinetobacter baumannii</i> is one of the main pathogens causing nosocomial and community-acquired infections. Tigecycline is an important antibiotic for the treatment of multidrug-resistant <i>A. baumannii</i> infections, but strains resistant to tigecycline have also emerged. There are still many unclear questions concerning the mechanism of tigecycline resistance in <i>A. baumannii</i>. In this study, tigecycline-susceptible and tigecycline-intermediate strains were gradually cultured with sub-minimum inhibitory concentrations of tigecycline to select for tigecycline-resistant mutants, and a tigecycline-resistant strain was cultured under 42 °C to select for tigecycline-susceptible mutants. We found that the acquisition of tigecycline resistance affected the susceptibility of the strains to other antibiotics. Resistance to ampicillin–sulbactam is negatively correlated with tigecycline resistance. The strains will experience fitness costs along with the acquisition of tigecycline resistance. Tigecycline resistance in the strains was not related to 16S rRNA target variation or outer membrane integrity alteration. By constructing a transposon mutation library, we found that transposon insertion of the <i>adeL</i> gene reduced the sensitivity of <i>A. baumannii</i> to tigecycline. This study provides important clues for understanding the mechanism of tigecycline resistance in <i>A. baumannii</i>. |
| first_indexed | 2024-03-09T20:50:45Z |
| format | Article |
| id | doaj.art-8dd4acd2885849e4aae85dc188082904 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T20:50:45Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-8dd4acd2885849e4aae85dc1880829042023-11-23T22:35:29ZengMDPI AGAntibiotics2079-63822022-10-011110137910.3390/antibiotics11101379Fitness Costs of Tigecycline Resistance in <i>Acinetobacter baumannii</i> and the Resistance Mechanism Revealed by a Transposon Mutation LibraryPing Wang0Hongou Wang1Cunwei Liu2Chengjie Feng3Qinghui Lu4Qinghua Zou5Department of Microbiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Microbiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Microbiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaPeking University People’s Hospital, Beijing 100044, ChinaDepartment of Microbiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Microbiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China<i>Acinetobacter baumannii</i> is one of the main pathogens causing nosocomial and community-acquired infections. Tigecycline is an important antibiotic for the treatment of multidrug-resistant <i>A. baumannii</i> infections, but strains resistant to tigecycline have also emerged. There are still many unclear questions concerning the mechanism of tigecycline resistance in <i>A. baumannii</i>. In this study, tigecycline-susceptible and tigecycline-intermediate strains were gradually cultured with sub-minimum inhibitory concentrations of tigecycline to select for tigecycline-resistant mutants, and a tigecycline-resistant strain was cultured under 42 °C to select for tigecycline-susceptible mutants. We found that the acquisition of tigecycline resistance affected the susceptibility of the strains to other antibiotics. Resistance to ampicillin–sulbactam is negatively correlated with tigecycline resistance. The strains will experience fitness costs along with the acquisition of tigecycline resistance. Tigecycline resistance in the strains was not related to 16S rRNA target variation or outer membrane integrity alteration. By constructing a transposon mutation library, we found that transposon insertion of the <i>adeL</i> gene reduced the sensitivity of <i>A. baumannii</i> to tigecycline. This study provides important clues for understanding the mechanism of tigecycline resistance in <i>A. baumannii</i>.https://www.mdpi.com/2079-6382/11/10/1379<i>Acinetobacter baumannii</i>tigecyclinemechanism of resistancefitness coststransposon mutation library |
| spellingShingle | Ping Wang Hongou Wang Cunwei Liu Chengjie Feng Qinghui Lu Qinghua Zou Fitness Costs of Tigecycline Resistance in <i>Acinetobacter baumannii</i> and the Resistance Mechanism Revealed by a Transposon Mutation Library Antibiotics <i>Acinetobacter baumannii</i> tigecycline mechanism of resistance fitness costs transposon mutation library |
| title | Fitness Costs of Tigecycline Resistance in <i>Acinetobacter baumannii</i> and the Resistance Mechanism Revealed by a Transposon Mutation Library |
| title_full | Fitness Costs of Tigecycline Resistance in <i>Acinetobacter baumannii</i> and the Resistance Mechanism Revealed by a Transposon Mutation Library |
| title_fullStr | Fitness Costs of Tigecycline Resistance in <i>Acinetobacter baumannii</i> and the Resistance Mechanism Revealed by a Transposon Mutation Library |
| title_full_unstemmed | Fitness Costs of Tigecycline Resistance in <i>Acinetobacter baumannii</i> and the Resistance Mechanism Revealed by a Transposon Mutation Library |
| title_short | Fitness Costs of Tigecycline Resistance in <i>Acinetobacter baumannii</i> and the Resistance Mechanism Revealed by a Transposon Mutation Library |
| title_sort | fitness costs of tigecycline resistance in i acinetobacter baumannii i and the resistance mechanism revealed by a transposon mutation library |
| topic | <i>Acinetobacter baumannii</i> tigecycline mechanism of resistance fitness costs transposon mutation library |
| url | https://www.mdpi.com/2079-6382/11/10/1379 |
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