1. Coexistence of a nonresistance-conferring IncI1 plasmid favors persistence of the bla CTX-M -bearing IncFII plasmid in Escherichia coli .
- Author
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He K, Lin J, Liang Y, Cui J, Chen Q, Dong Y, Ma X, He D, and Yuan L
- Subjects
- Anti-Bacterial Agents pharmacology, Escherichia coli Proteins genetics, Escherichia coli Proteins metabolism, Escherichia coli Infections microbiology, Microbial Sensitivity Tests, Humans, Escherichia coli genetics, Plasmids genetics, beta-Lactamases genetics, beta-Lactamases metabolism
- Abstract
The interaction between coexisting plasmids can affect plasmid-carried resistance gene persistence and spread. However, whether the persistence of the bla
CTX-M gene in clinical Enterobacteriaceae is related to the interaction of coresident nonresistance-conferring plasmids has not been reported. This study was initiated to elucidate how a nonresistance-conferring IncI1 plasmid affected the blaCTX-M -bearing IncFII plasmid colocated on the same cell. Herein, we constructed three isogenic derivatives of E. coli C600, designated as C600FII , C600I1 , and C600FII+I1 , which harbored the blaCTX-M -IncFII plasmid and/or the nonresistance-IncI1 one. We discovered that strain C600FII+I1 conferred higher fitness advantages than strain C600FII ; also, the stability of the blaCTX-M -IncFII plasmid was noticeably improved in an antibiotic-free environment when it coexisted with the IncI1 plasmid. To further explore why the IncI1 plasmid enhanced the persistence of the blaCTX-M -IncFII plasmid, we assessed the blaCTX-M -IncFII plasmid's copy numbers, conjugation frequencies, and rep gene expressions in strains C600FII and C600FII+I1 . The results demonstrated that the rep expressions of the blaCTX-M -IncFII plasmid in strain C600FII+I1 was greatly decreased, along with the plasmid's copy numbers and mating efficiencies, compared to those in strain C600FII . Moreover, further study revealed that the intracellular ATP levels of strain C600FII+I1 were far lower than those of strain C600FII . Our findings confirmed that coexistence of the nonresistance-IncI1 plasmid can keep the blaCTX-M -IncFII plasmid more stable by increasing the fitness advantages of the host bacteria, which will pose a threat to preventing the long-term presence of the plasmid-carried blaCTX-M gene in clinical Enterobacteriaceae., Importance: So far, plasmid-carried blaCTX-M is still the most common extended-spectrum beta-lactamase (ESBL) genotype in clinical settings worldwide. Except for the widespread use of third-generation cephalosporins, the interaction between coexisting plasmids can also affect the long-term stable existence of the blaCTX-M gene; however, the study on that is still sparse. In the present study, we assess the interaction of coinhabitant plasmids blaCTX-M -IncFII and nonresistance-IncI1. Our results confirmed that the increased fitness advantages of strain C600FII+I1 were attributable to the cohabitant nonresistance-IncI1 plasmid, which largely reduced the intracellular ATP levels of host bacteria, thus decreasing the rep gene expression of the blaCTX-M -IncFII plasmid, its copy numbers, and mating efficiencies, while the higher fitness advantages of strain C600FII+I1 enhanced the persistence of the blaCTX-M -IncFII plasmid. The results indicate that the nonresistance-IncI1 plasmid contributes to the long-term existence of the blaCTX-M -IncFII plasmid, implying a potentially new strategy for controlling the spread of resistance plasmids in clinical settings by targeting nonresistance plasmids., Competing Interests: The authors declare no conflict of interest.- Published
- 2024
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