Impact of Plasmid-Encoded H-NS–like Protein on blaNDM-1-Bearing IncX3 Plasmid in Escherichia coli

Liu, Baomo; Shui, Lili; Zhou, Kai; Jiang, Ying; Li, Xiaoyü; Guan, Jing; Li, Qi; Zhuo, Chao

doi:10.1093/infdis/jiz567

Cited by 19 publications

(31 citation statements)

References 25 publications

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“…In this study, three strains of bla NDM-5 -positive E. coli were detected in IncX3 plasmid. Genomic sequence analysis showed that the IncX3 plasmid was highly similar to that reported in the Enterobacteriaceae such as E. coli and Klebsiella pneumoniae from human clinic, environment and food animals published in the database [18,19], suggesting that IncX3 plasmid has been widely prevalent.…”

Section: Discussionsupporting

confidence: 62%

Emergence of IncHI2 Plasmid-Harboring blaNDM-5 from Porcine Escherichia coli Isolates in Guangdong, China

et al. 2021

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Carbapenem resistance has posed potential harmful risks to human and animals. The objectives of this study were to understand the prevalence of blaNDM-5 in pigs and investigate the molecular characteristics of NDM-5-producing Escherichia coli isolates in Guangdong province in China. Carbapenem-resistant E. coli isolates were isolated from pigs and obtained using MacConkey plates containing 0.5 mg/L meropenem. Conjugation assay and antimicrobial susceptibility testing were conducted for the isolates and their transconjugants. Whole-genome sequence (WGS) was used to analyze the plasmid genetic feature. A total of five blaNDM-5-carrying E. coli isolates were obtained in the present investigations. They belonged to five ST types. The blaNDM-5 genes were found to be in IncX3 and IncHI2 plasmid. The IncX3 plasmid was 46,161 bp in size and identical to other reports. IncHI2 plasmid was 246,593 bp in size and similar to other IncHI2-ST3 plasmids. It consisted of a typical IncHI2 plasmid backbone region and a multiresistance region (MRR). The blaNDM-5 was closely associated with the IS3000-ISAba125-blaNDM-5-bleMBL-trpF-tat-IS26 unit. We first reported the blaNDM-5-carrying IncHI2 in E. coli isolates recovered from pigs and revealed the molecular characterization. Continued surveillance for the dissemination of blaNDM-5 among food-producing animals is required.

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Section: Discussionsupporting

confidence: 62%

Emergence of IncHI2 Plasmid-Harboring blaNDM-5 from Porcine Escherichia coli Isolates in Guangdong, China

et al. 2021

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“…plasmids, the absence of a plasmid-encoded H-NS-like protein up-regulates the expression of transfer genes through an uncharacterized pathway, causing a 2.5-fold increase in transfer frequency of IncX3 plasmids (33). Thus, PixR is the first transcriptional activator of transfer genes identified in IncX plasmids, which expands our knowledge of the conjugation of IncX plasmids.…”

Section: Discussionmentioning

confidence: 85%

PixR, a novel activator of conjugative transfer of IncX4 resistance plasmids, mitigates the fitness cost of mcr-1 carriage in Escherichia coli

Durand

Grenier

et al. 2021

Preprint

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The emergence of the plasmid-borne colistin resistance gene mcr-1 threats public health. IncX4-type plasmids are one of the most epidemiologically successful vehicles for spreading mcr-1 worldwide. Since MCR-1 is known for imposing a fitness cost to its host bacterium, the successful spread of mcr-1-bearing plasmids might be linked to high conjugation frequency, which would enhance the maintenance of the plasmid in the host without antibiotic selection. However, the mechanism of IncX4 plasmids conjugation remains unclear. In this study, we used high-density transposon mutagenesis to identify factors required for IncX4 plasmid transfer and 18 genes were identified, including five with annotations unrelated to conjugation. The Cappable-seq and RNA-seq analysis confirmed that a novel transcriptional regulator gene, pixR, directly regulates the transfer of IncX4 plasmids by binding the promoter of 13 essential transfer genes to increase their transcription. Plasmid invasion and co-culture competition assays revealed that pixR is essential for the spread and persistence of mcr-1-bearing IncX4 plasmids in bacterial populations, and effective conjugation is crucial for alleviating the fitness cost exerted by mcr-1 carriage. The existence of the IncX4-specific pixR gene increases plasmid transmissibility while promoting the invasion and persistence of mcr-1-bearing plasmids in bacterial populations, which helps explain their global prevalence.IMPORTANCEThe spread of clinical important antibiotic resistance genes is frequently related to some epidemic plasmids. However, the underlying molecular mechanisms contributing to the successful spread of these epidemic plasmids remains unclear. The significant of our research indicated that efficient conjugation could promote the invasion and persistence of plasmids within a bacterial population, resulting in the successful dissemination of epidemic plasmids in nature. Our data also highlight the importance of developing plasmid conjugation inhibitors to solve the antibiotic resistance crisis.

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“…According to a previous method ( Liu et al, 2020 ), overnight cultures of strains carrying pRF14-1, pSC4R, pHS14-2, and its recipient bacteria were diluted 1:1,000 into fresh LB broth and were incubated at 37°C with 200 rpm for 12 h. Growth curves were obtained by measuring the optical density of cultures at 620 nm every hour by Multiskan FC (Thermo Fisher Scientific). All experiments were conducted in triplicate and repeated three times independently, and the average values were used to estimate growth parameters.…”

Section: Methodsmentioning

confidence: 99%

“…It was found that some plasmids also have genes encoding H-NS family proteins, and the deletion of hns decreases the fitness of host bacteria ( Doyle et al, 2007 ), indicating that H-NS is likely to mediate the fitness cost of plasmids. A recent study showed that H-NS plays an important role in the dissemination of bla NDM– 1 -bearing IncX3 Plasmid in Escherichia coli by regulating the expression of plasmid-related genes ( Liu et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Histone-Like Nucleoid Structuring Protein Modulates the Fitness of tet(X4)-Bearing IncX1 Plasmids in Gram-Negative Bacteria

et al. 2021

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The emergence of plasmid-mediated tigecycline resistance gene tet(X4) poses a challenging threat to public health. Based on the analysis of tet(X4)-positive plasmids in the NCBI database, we found that the IncX1-type plasmid is one of the most common vectors for spreading tet(X4) gene, but the mechanisms by which these plasmids adapt to host bacteria and maintain the persistence of antibiotic resistance genes (ARGs) remain unclear. Herein, we investigated the underlying mechanisms of how host bacteria modulate the fitness cost of IncX1 plasmids carrying tet(X4) gene. Interestingly, we found that the tet(X4)-bearing IncX1 plasmids encoding H-NS protein imposed low or no fitness cost in Escherichia coli and Klebsiella pneumoniae; instead, they partially promoted the virulence and biofilm formation in host bacteria. Regression analysis revealed that the expression of hns gene in plasmids was positively linked to the relative fitness of host bacteria. Furthermore, when pCE2::hns was introduced, the fitness of tet(X4)-positive IncX1 plasmid pRF55-1 without hns gene was significantly improved, indicating that hns mediates the improvement of fitness. Finally, we showed that the expression of hns gene is negatively correlated with the expression of tet(X4) gene, suggesting that the regulatory effect of H-NS on adaptability may be attributed to its inhibitory effect on the expression of ARGs. Together, our findings suggest the important role of plasmid-encoded H-NS protein in modulating the fitness of tet(X4)-bearing IncX1 plasmids, which shed new insight into the dissemination of tet(X4) gene in a biological environment.

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Impact of Plasmid-Encoded H-NS–like Protein on blaNDM-1-Bearing IncX3 Plasmid in Escherichia coli

Cited by 19 publications

References 25 publications

Emergence of IncHI2 Plasmid-Harboring blaNDM-5 from Porcine Escherichia coli Isolates in Guangdong, China

Emergence of IncHI2 Plasmid-Harboring blaNDM-5 from Porcine Escherichia coli Isolates in Guangdong, China

PixR, a novel activator of conjugative transfer of IncX4 resistance plasmids, mitigates the fitness cost of mcr-1 carriage in Escherichia coli

Histone-Like Nucleoid Structuring Protein Modulates the Fitness of tet(X4)-Bearing IncX1 Plasmids in Gram-Negative Bacteria

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