Biology subjects

Dao, T. D.

Publications and source records attributed to Dao, T. D..

4 recordsLinked to original sources

bioRxiv2026

Tracing the emergence of the novel fluoroquinolone resistance gene qrtA in enterococci through environmental reservoirs and pELF-type linear plasmids

As animal hosts adapted to land, Enterococcus species diverged from a common ancestor shared with Vagococcus species by acquiring genes essential for survival and transmission in the exposed arid environment. In addition to their intrinsic ruggedness, human-associated enterococci now frequently exhibit multidrug resistance, largely driven by the accumulation of antimicrobial resistance genes (ARGs) on mobile genetic elements (MGEs). However, the source of these resistance elements, their diversity in natural reservoirs, and the risk that they pose remain unclear. To investigate the movement of novel ARGs from the environmental reservoir and the elements that convey them into clinically important enterococcal lineages, we examined environmental vancomycin-resistant enterococci (VRE) circulating in a polluted urban river in Hanoi, Vietnam. Whole-genome sequencing of VRE isolates revealed multidrug-resistance pELF-type linear plasmids harboring a novel fluoroquinolone resistance gene (qrtA) encoding a major facilitator superfamily transporter. The qrtA gene appears to have originated on Vagococcus chromosomes and to have been mobilized by IS1216E-associated MGEs. Vagococcus genomes show strong associations between ARGs, IS1216E, and plasmids related to those in enterococci, and conjugation experiments demonstrated that pELF-type linear plasmids can transfer between Enterococcus and Vagococcus without major fitness costs, positioning them as plausible vehicles for importing environmental ARGs into enterococci. Reconstruction of pELF-type linear plasmid evolution in the environment, together with database mining of rare qrtA-positive clinical isolates from Asia and Europe, suggests that qrtA-bearing pELF-type linear plasmids are in an early phase of global dissemination. These findings highlight the need for coordinated international One Health surveillance of ARG and MGE dynamics, including emerging determinants such as qrtA, together with proactive interventions to limit their spread.

microbiology↗

bioRxiv2022

Strand-biased circularizing integrative elements spread tmexCD-toprJ gene clusters encoding RND-type multidrug efflux pumps by repeated transpositions

Antimicrobial resistance genes (ARGs) are associated with mobile genetic elements (MGEs) that conscript useful genes into the human-microbe and microbe-microbe battlefields. Thus, under intense selective pressure, ARGs have been constantly adapting and evolving, spreading among microbes. tmexCD-toprJ gene clusters, which encode resistance-nodulation-cell division (RND)-type efflux pumps, confer multidrug-resistance to clinically important antimicrobials, including tigecycline. Noteworthily, these gene clusters have emerged in gram-negative bacteria in humans, animals, and the environment worldwide by MGE-mediated transfer. Here we show a hidden MGE, strand-biased circularizing integrative element (SE), that is recently recognized to mediate transpositions of ARGs, associated with the spread of tmexCD-toprJ gene clusters. We identified multidrug-resistant isolates of Aeromonas species in a water environment in Vietnam that harbored multiple copies of tmexCD-toprJ in their chromosomes that were associated with SEs. In particular, Aeromonas hydrophila NUITM-VA1 was found to harbor two copies of a novel variant of tmexC3.3D3.3-topJ1 within cognate SEs, whereas Aeromonas caviae NUITM-VA2 harbored four copies of a novel variant of tmexC2D2.3-topJ2 within cognate SEs. Based on the nature of SE to incorporate a neighboring sequence into the circular form and reinsert it into target sites during transposition, we identified the order of intragenomic movements of tmexCD-toprJ gene clusters. Altogether, our findings suggest that most known subgroups of tmexCD-toprJ and their subvariants underwent transpositions among bacterial chromosomes and plasmids via SEs. Hence, a tmexCD-toprJ gene cluster ancestor may have been initially mobilized via SE, subsequently spreading among bacteria and evolving in new hosts.

microbiology↗

bioRxiv2022

Emergence of plasmid-mediated RND-type efflux pump gene cluster tmexCD-toprJ in Shewanella xiamenensis in a water environment

The emergence of the mobile resistance-nodulation-division (RND)-type efflux pump tmexCD-toprJ gene cluster that confers multidrug resistance (MDR), including tigecycline resistance, in gram-negative bacteria poses a global public health threat. However, the spread of such clinically important antimicrobial resistance genes (ARGs) in the natural environment has not yet been well investigated. In this study, we investigated MDR aquatic bacteria in Vietnam. A carbapenem- and tigecycline-resistant Shewanella xiamenensis isolate NUITM-VS2 was obtained from urban drainage in Hanoi, Vietnam, in October 2021. S. xiamenensis NUITM-VS2 showed resistance to most antimicrobials tested, including tigecycline, tetracyclines, carbapenems, cephalosporins, fluoroquinolone, and aminoglycosides. Whole-genome analysis was performed by long- and short-read sequencing, resulting in the complete genome sequence consisting of one chromosome and five plasmid sequences. ARGs and plasmid replicons in the genome were detected using ResFinder with the custom ARG database, including all known tigecycline resistance genes, and PlasmidFinder, respectively. A 152.2-kb IncC plasmid, pNUITM-VS2_2, co-carried two mobile tigecycline resistance genes, tet(X4) and tmexC3.2D3.2-toprJ1. In addition, a 24.8-kb untypeable plasmid, pNUITM-VS2_4, carried the carbapenemase gene blaNDM-1. pNUITM-VS2_2 was transferred to Escherichia coli by conjugation, which simultaneously conferred high-level resistance against many antimicrobials, including tigecycline. To the best of our knowledge, this is the first report of the detection of the mobile RND-type efflux pump gene cluster tmexCD-toprJ in Shewanella species. Our results provide genetic evidence of the complexity of the dynamics of clinically important ARGs among aquatic bacteria, which could be important reservoirs for ARGs in the natural environment.

microbiology↗

bioRxiv2021

A transferable IncC-IncX3 hybrid plasmid co-carrying blaNDM-4, tet(X4), and tmexCD3-toprJ3 confers resistance to carbapenem and tigecycline

Tigecycline is a last-resort antimicrobial that exhibits promising activity against carbapenemase-producing Enterobacterales (CPE). However, mobile tigecycline resistance genes, tet(X) and tmexCD-toprJ, have emerged in China and have spread possibly worldwide. Tet(X) family proteins, Tet(X3) to Tet(X14), function as tigecycline-inactivating enzymes, and TMexCD-TOprJ complexes function as efflux pumps for tigecycline. Here, we report a CPE isolate co-harboring both emerging tigecycline resistance factors for the first time. A carbapenem- and tigecycline-resistant Klebsiella aerogenes NUITM-VK5 was isolated from an urban drainage in Vietnam in 2021 and a plasmid pNUITM-VK5_mdr co-carrying tet(X4) and tmexCD3-toprJ3 along with the carbapenemase gene blaNDM-4 was identified in NUITM-VK5. pNUITM-VK5_mdr was transferred to Escherichia coli by conjugation and simultaneously conferred high-level resistance against multiple antimicrobials, including carbapenems and tigecycline. An efflux pump inhibitor canceled TMexCD3-TOprJ3-mediated tigecycline resistance, suggesting that both tigecycline resistance factors independently and additively contribute to the high-level resistance. The plasmid had the IncX3 and IncC replicons and was estimated to be a hybrid of plasmids with different origins. Unlike IncX3 plasmids, IncC plasmids are stably maintained in an extremely broad range of bacterial hosts in humans, animals, and environment. Thus, future global spread of multidrug-resistance plasmids such as pNUITM-VK5_mdr poses a public health crisis.

microbiology↗