Metformin Reverses tmexCD1-toprJ1- and tet(A)-Mediated High-Level Tigecycline Resistance in K. pneumoniae
Abstract
:1. Introduction
2. Materials and Methods
2.1. Bacteria and Reagents
2.2. MIC Determination
2.3. Checker Board Assay
2.4. Time–Killing Curve
2.5. The Proton Motive Force Assay
2.6. Efflux Pump Assay
2.7. Tigecycline Intracellar Accumulation Analysis
2.8. Galleria Mellonella Infection Model
2.9. Data Analysis
3. Results
3.1. The In Vitro Synergistic Activity of Tigecycline and Metformin against tmexCD1-toprJ1 and tet(A) Mutant Positive Strains
3.2. Metformin Deprives the Function of Efflux Pump and Facilitate the Intracellular Accumulation of Tigecycline
3.3. Metformin Potentiates In Vivo Efficacy of Tigecycline Using Galleria Mellonella Infection Model
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Strain | Resistance Gene | Sources | MIC (;µg/mL) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
GEN | CFF | CIP | ENR | TET | TGC | DOX | MET | MER | CL | KAN | |||
RGT9-1 | tmexCD1-toprJ1,oqxAB, QnrB4, QnrS1, aac(3)-IId, aac(6’)Ib-cr, aadA16, aadA2 | Swine Faeces | 128 | 8 | 8 | 8 | >128 | 64 | 64 | 50 mg | ≤0.25 | ≤0.25 | >256 |
RGF15-2-1 | tmexCD1-toprJ1,oqxAB, QnrB4, QnrS1, aac(3)-IId, aac(6’)Ib-cr, aadA16, aadA2 | Swine Faeces | 128 | 16 | 8 | 8 | >128 | 64 | 64 | 50 mg | ≤0.25 | ≤0.25 | >256 |
RGF-131 | tet(A), QnrS1, aac(3)-IId, aac(6’)Ib-cr, aadA16, aadA1, blaCTX-M-55, blaSHV-11, blaSHV-1 | Swine Faeces | 64 | 4 | 4 | 4 | >128 | 32 | 64 | 50 mg | ≤0.25 | ≤0.25 | >256 |
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Xiao, X.; Huan, Q.; Huang, Y.; Liu, Y.; Li, R.; Xu, X.; Wang, Z. Metformin Reverses tmexCD1-toprJ1- and tet(A)-Mediated High-Level Tigecycline Resistance in K. pneumoniae. Antibiotics 2022, 11, 162. https://doi.org/10.3390/antibiotics11020162
Xiao X, Huan Q, Huang Y, Liu Y, Li R, Xu X, Wang Z. Metformin Reverses tmexCD1-toprJ1- and tet(A)-Mediated High-Level Tigecycline Resistance in K. pneumoniae. Antibiotics. 2022; 11(2):162. https://doi.org/10.3390/antibiotics11020162
Chicago/Turabian StyleXiao, Xia, Quanmin Huan, Yanhu Huang, Yuan Liu, Ruichao Li, Xilan Xu, and Zhiqiang Wang. 2022. "Metformin Reverses tmexCD1-toprJ1- and tet(A)-Mediated High-Level Tigecycline Resistance in K. pneumoniae" Antibiotics 11, no. 2: 162. https://doi.org/10.3390/antibiotics11020162
APA StyleXiao, X., Huan, Q., Huang, Y., Liu, Y., Li, R., Xu, X., & Wang, Z. (2022). Metformin Reverses tmexCD1-toprJ1- and tet(A)-Mediated High-Level Tigecycline Resistance in K. pneumoniae. Antibiotics, 11(2), 162. https://doi.org/10.3390/antibiotics11020162