Genomic insights into linezolid-resistant Enterococci revealed its evolutionary diversity and poxtA copy number heterogeneity

Wang, Qiaojun; Peng, Kai; Liu, Ziyi; Li, Yan; Xiao, Xia; Du, Xiang-Dang; Li, Ruichao; Wang, Zhiqiang

doi:10.1016/j.ijantimicag.2023.106929

Cited by 5 publications

(1 citation statement)

References 42 publications

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“…To the best of our knowledge, it has not been reported that RLS can have such inhibitory effects on poxtA expression. Wang et al suggested that the accumulation of the poxtA gene in LRE isolates may lead to an increase in poxtA expression, thus providing the bacteria with an adaptive advantage in the presence of linezolid [48]. Considering that the ABC transporter domain-containing protein encoded by poxtA is involved in ATP binding, ATP hydrolysis, and transmembrane translocation, it suggested that this decrease in expression may inhibit these cellular activities, thereby mitigating the emergence of enterococci resistance to linezolid.…”

Section: Discussionmentioning

confidence: 99%

The Synergistic Activity of Rhamnolipid Combined with Linezolid against Linezolid-Resistant Enterococcus faecium

Chang,

Chen,

et al. 2023

Molecules

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Enterococci resistance is increasing sharply, which poses a serious threat to public health. Rhamnolipids are a kind of amphiphilic compound used for its bioactivities, while the combination of nontraditional drugs to restore linezolid activity is an attractive strategy to treat infections caused by these pathogens. This study aimed to investigate the activity of linezolid in combination with the rhamnolipids against Enterococcus faecium. Here, we determined that the rhamnolipids could enhance the efficacy of linezolid against enterococci infections by a checkerboard MIC assay, a time–kill assay, a combined disk test, an anti-biofilm assay, molecular simulation dynamics, and mouse infection models. We identified that the combination of rhamnolipids and linezolid restored the linezolid sensitivity. Anti-biofilm experiments show that our new scheme can effectively inhibit biofilm generation. The mouse infection model demonstrated that the combination therapy significantly reduced the bacterial load in the feces, colons, and kidneys following subcutaneous administration. This study showed that rhamnolipids could play a synergistic role with linezolid against Enterococcus. Our combined agents could be appealing candidates for developing new combinatorial agents to restore antibiotic efficacy in the treatment of linezolid-resistant Enterococcus infections.

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Section: Discussionmentioning

confidence: 99%

The Synergistic Activity of Rhamnolipid Combined with Linezolid against Linezolid-Resistant Enterococcus faecium

Chang,

Chen,

et al. 2023

Molecules

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Compensatory evolution of chromosomes and plasmids counteracts the plasmid fitness cost

Liu,

Zhao,

et al. 2024

Ecology and Evolution

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Plasmids incur a fitness cost that has the potential to restrict the dissemination of resistance in bacterial pathogens. However, bacteria can overcome this disadvantage by compensatory evolution to maintain their resistance. Compensatory evolution can occur via both chromosomes and plasmids, but there are a few reviews regarding this topic, and most of them focus on plasmids. In this review, we provide a comprehensive overview of the currently reported mechanisms underlying compensatory evolution on chromosomes and plasmids, elucidate key targets regulating plasmid fitness cost, and discuss future challenges in this field. We found that compensatory evolution on chromosomes primarily arises from mutations in transcriptional regulatory factors, whereas compensatory evolution of plasmids predominantly involves three pathways: plasmid copy number regulation, conjugation transfer efficiency, and expression of antimicrobial resistance (AMR) genes. Furthermore, the importance of reasonable selection of research subjects and effective integration of diverse advanced research methods is also emphasized in our future study on compensatory mechanisms. Overall, this review establishes a theoretical framework that aims to provide innovative ideas for minimizing the emergence and spread of AMR genes.

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Molecular epidemiology, phenotypic and genomic characterization of antibiotic-resistant enterococcal isolates from diverse farm animals in Xinjiang, China

Chen,

Wang,

et al. 2024

Science of The Total Environment

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Genomic insights into linezolid-resistant Enterococci revealed its evolutionary diversity and poxtA copy number heterogeneity

Cited by 5 publications

References 42 publications

The Synergistic Activity of Rhamnolipid Combined with Linezolid against Linezolid-Resistant Enterococcus faecium

The Synergistic Activity of Rhamnolipid Combined with Linezolid against Linezolid-Resistant Enterococcus faecium

Compensatory evolution of chromosomes and plasmids counteracts the plasmid fitness cost

Molecular epidemiology, phenotypic and genomic characterization of antibiotic-resistant enterococcal isolates from diverse farm animals in Xinjiang, China

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