Characterization of Fitness Cost Caused by Tigecycline-Resistance Gene tet(X6) in Different Host Bacteria

Jiang, Lijie; Cai, Weiping; Tang, Feifei; Wang, Zhiqiang; Lv, Yuan

doi:10.3390/antibiotics10101172

Cited by 10 publications

(4 citation statements)

References 28 publications

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“…This sharp contrast implied that the high-level expression of tet (X4) may arise biosynthetic burden for host bacteria. Previous study has demonstrated the expression of tet (X6) exerted high fitness cost in E. coli as well ( Jiang et al, 2021 ), suggesting the expression of tet (X) variants may be positively correlated with fitness cost. Second, an elevated conjugation frequency was observed in both evolved strains, and the expression of genes involving in the conjugative process was increased as well.…”

Section: Discussionmentioning

confidence: 99%

Persistence of plasmid and tet(X4) in an Escherichia coli isolate coharboring blaNDM-5 and mcr-1 after acquiring an IncFII tet(X4)-positive plasmid

Xiao

Liu²,

Chen³

et al. 2022

Front. Microbiol.

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The prevalence of plasmid-mediated tigecycline resistance gene tet(X4) is presenting an increasing trend. Once tet(X4)-bearing plasmids are captured by multidrug-resistant bacteria, such as blaNDM and mcr-coharboring bacteria, it will promote bacteria to develop an ultra-broad resistance spectrum, limiting clinical treatment options. However, little is known about the destiny of such bacteria or how they will evolve in the future. Herein, we constructed a multidrug-resistant bacteria coharboring tet(X4), blaNDM-5, and mcr-1 by introducing a tet(X4)-bearing plasmid into a blaNDM-5 and mcr-1 positive E. coli strain. Subsequently, the stability of tet(X4) and the plasmid was measured after being evolved under tigecycline or antibiotic-free circumstance. Interestingly, we observed both tet(X4)-bearing plasmids in tigecycline treated strains and non-tigecycline treated strains were stable, which might be jointly affected by the increased conjugation frequency and the structural alterations of the tet(X4)-positive plasmid. However, the stability of tet(X4) gene showed different scenarios in the two types of evolved strains. The tet(X4) gene in non-tigecycline treated strains was stable whereas the tet(X4) gene was discarded rapidly in tigecycline treated strains. Accordingly, we found the expression levels of tet(X4) gene in tigecycline-treated strains were several times higher than in non-tigecycline treated strains and ancestral strains, which might in turn impose a stronger burden on the host bacteria. SNPs analysis revealed that a myriad of mutations occurred in genes involving in conjugation transfer, and the missense mutation of marR gene in chromosome of tigecycline treated strains might account for the completely different stability of tet(X4)-bearing plasmid and tet(X4) gene. Collectively, these findings shed a light on the possibility of the emergence of multidrug resistant bacteria due to the transmission of tet(X4)-bearing plasmid, and highlighted that the antibiotic residues may be critical to the development of such bacteria.

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Section: Discussionmentioning

confidence: 99%

Persistence of plasmid and tet(X4) in an Escherichia coli isolate coharboring blaNDM-5 and mcr-1 after acquiring an IncFII tet(X4)-positive plasmid

Xiao

Liu²,

Chen³

et al. 2022

Front. Microbiol.

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“…As mentioned previously, 31 a competition experiment of the strains was carried out. Briefly, the mixed bacterial liquid of NO.22 and NO.22R (1:1) was cultured under the above conditions, and cultured bacteria were sucked at 0, 4, 8, 12, 24, and 48 h. The CFU of the culture solution was counted on an agar plate and an agar plate containing 1 × MIC fosfomycin for 24 h. Fitness was calculated using a competition experiment, and the relative fitness (W) of the mutant to wild type was calculated as follows:…”

Section: Methodsmentioning

confidence: 99%

Assessing the Emergence of Resistance in vitro and Invivo: Linezolid Combined with Fosfomycin Against Fosfomycin-Sensitive and Resistant Enterococcus

Li¹,

Peng²,

Zhang³

et al. 2022

IDR

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Purpose We aimed to evaluate the synergistic effect of linezolid and fosfomycin on fosfomycin-sensitive and -resistant Enterococcus clinical isolates in vitro and in vivo and whether the emergence of fosfomycin resistance in Enterococcus is associated with changes in strain virulence, from the perspective of fitness cost. Methods The synergistic effect of linezolid and fosfomycin was studied via in vitro checkerboard and static time-kill assays, as well as based on the in vivo survival rate and hemolymph load of a Galleria mellonella infection model. Fosfomycin resistance was induced via a stepwise increase in concentration. Changes in the virulence of the strains after drug resistance were investigated using the G. mellonella infection model and reverse transcription quantitative polymerase chain reaction (RT-qPCR). In vitro and in vivo growth curves and competitive experiments were used to study the fitness cost of the strain. Finally, a static time-kill assay was performed to explore the effect of the combined medication. Results In vitro and in vivo data showed that linezolid combined with fosfomycin had a good synergistic effect on Enterococcus treatment. The G. mellonella infection model and RT-qPCR data showed that the virulence of the resistant strains was weakened to varying degrees. A survival curve and competition experimental data showed that this was related to the fitness cost of strains while acquiring resistance and negatively impacted linezolid treatment; however, the combination still showed a good synergistic effect in drug-resistant strains. Conclusion Linezolid combined with fosfomycin had a synergistic effect on both fosfomycin-sensitive and -resistant Enterococcus strains. Strains incur fitness costs as they develop drug resistance, which leads to a decrease in virulence. There is an interaction between fitness cost, virulence, and drug resistance, which indirectly affects drug treatment.

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“…pneumoniae harboring mobile tmexCD1-toprJ isolated from microbial enumerations of hospitalized patients have been reported ( Sun S. et al, 2020 ; He et al, 2021 ; Qin et al, 2021 ; Yang et al, 2021 ; Liu et al, 2022 ), particularly recovered from diverse ecological niches from different world regions ( Tables 1 , 3 ). Additionally, the presence of VAGs in the MTR gene-bearing strains could confer a fitness advantage to the organisms ( Jiang et al, 2021 ).…”

Section: Distribution Reservoirs and Traits Of Mobile Tigecycline Res...mentioning

confidence: 99%

Mobile Tigecycline Resistance: An Emerging Health Catastrophe Requiring Urgent One Health Global Intervention

et al. 2022

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Mobile tigecycline resistance (MTR) threatens the clinical efficacy of the salvage antibiotic, tigecycline (TIG) used in treating deadly infections in humans caused by superbugs (multidrug-, extensively drug-, and pandrug-resistant bacteria), including carbapenem- and colistin-resistant bacteria. Currently, non-mobile tet(X) and mobile plasmid-mediated transmissible tet(X) and resistance-nodulation-division (RND) efflux pump tmexCD-toprJ genes, conferring high-level TIG (HLT) resistance have been detected in humans, animals, and environmental ecosystems. Given the increasing rate of development and spread of plasmid-mediated resistance against the two last-resort antibiotics, colistin (COL) and TIG, there is a need to alert the global community on the emergence and spread of plasmid-mediated HLT resistance and the need for nations, especially developing countries, to increase their antimicrobial stewardship. Justifiably, MTR spread projects One Health ramifications and portends a monumental threat to global public and animal health, which could lead to outrageous health and economic impact due to limited options for therapy. To delve more into this very important subject matter, this current work will discuss why MTR is an emerging health catastrophe requiring urgent One Health global intervention, which has been constructed as follows: (a) antimicrobial activity of TIG; (b) mechanism of TIG resistance; (c) distribution, reservoirs, and traits of MTR gene-harboring isolates; (d) causes of MTR development; (e) possible MTR gene transfer mode and One Health implication; and (f) MTR spread and mitigating strategies.

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Characterization of Fitness Cost Caused by Tigecycline-Resistance Gene tet(X6) in Different Host Bacteria

Cited by 10 publications

References 28 publications

Persistence of plasmid and tet(X4) in an Escherichia coli isolate coharboring blaNDM-5 and mcr-1 after acquiring an IncFII tet(X4)-positive plasmid

Persistence of plasmid and tet(X4) in an Escherichia coli isolate coharboring blaNDM-5 and mcr-1 after acquiring an IncFII tet(X4)-positive plasmid

Assessing the Emergence of Resistance in vitro and Invivo: Linezolid Combined with Fosfomycin Against Fosfomycin-Sensitive and Resistant Enterococcus

Mobile Tigecycline Resistance: An Emerging Health Catastrophe Requiring Urgent One Health Global Intervention

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