Public Health

Evidence brief: Structural insights into the mosaic and modular organization of fourteen co-occurring resistance genes in multidrug resistant Enterobacteriaceae

A sourced PLOS One study, published 2026-08-26. Read the researchers’ findings, methods and context, with links to connected African health evidence.

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Published in PLOS One on 2026-08-26, this study is presented as an attributed evidence briefing. The excerpts below are the original researchers’ words, reproduced under their Creative Commons Attribution licence. HealthSignal has selected the abstract and, where needed, opening background paragraphs; the complete methods, results, limitations and references remain in the linked paper.

Original authors: Connor A. J. Rossel, Lieke B. van Alphen, Edou R. Heddema, Paul H. M. Savelkoul

Source: PLOS One • DOI 10.1371/journal.pone.0355393

Read the complete primary study ↗ · Creative Commons Attribution licence

From the researchers

Abstract

Up to 14 co-occurring antimicrobial resistance genes (ARG) were previously detected in multiple outbreaks in the Netherlands involving various Enterobacteriaceae species, clones and plasmids, but similar multidrug resistance regions (MRR). This study aimed to map the reported occurrence, mosaic and modular genetic context of the involved ARG. Google Scholar and PubMed Central were queried for articles describing long-read assemblies with ≥ 6 co-occurring ARG. Plasmid (n = 119) and chromosomal (n = 8) sequences of 9 bacterial taxa originating from North America (n = 39), Europe (n = 34), Africa (n = 16), Asia (n = 14), Oceania (n = 13) and South America (n = 7) were extracted from NCBI. Based on colocalized insertions sequences, transposons and integrons, the ARGs could be divided into nine distinct resistance elements. These elements presented a total of 118 mosaic structural variants (SV): qnrB1 (SV = 27; n = 102), blaCTX‑M‑15 (SV = 23; n = 137), tet(A) (SV = 18; n = 93), dfrA14 (SV = 14; n = 115), sul2—strA—strB (SV = 13; n = 120), blaTEM‑1b (SV = 12; n = 119), aac(6’)‑Ib‑cr—blaOXA‑1—catB3 (SV = 7; n = 137), aac(3)‑IIe (SV = 2; n = 92), and aadA1—catA1 SV = 2; n = 12). The MRR showed high modularity with no clear ARG order. Still, three frequent sub-configurations were found. Firstly, blaTEM‑1b was flanked by sul2—strA—strB downstream (92.6%) and blaCTX‑M‑15 upstream (84.0%). Secondly, qnrB1 was flanked by tet(A) upstream (62.4%) and dfrA14 (63.4%) downstream. Thirdly, aac(3)‑IIe was flanked by aac(6’)‑Ib‑cr—blaOXA‑1—catB3 upstream (80.4%). In conclusion, the 14 ARG co-occur globally in similar MRR that are complex to interpret due to modularity and mosaicism. Still, the preservation of these clinically relevant resistance elements infers a potential means of transfer between distinct Enterobacteriaceae isolates.

Introduction

Antimicrobial resistance (AMR) in bacterial pathogens is a major global burden that is associated with and attributable to patient mortality [1]. This challenge is compounded by the increasing co-occurrence of antimicrobial resistance genes (ARG), which has led to a rise in difficult-to-treat multidrug resistant (MDR) bacteria. To manage infections caused by these bacteria, there has been an urgent need for the development of novel therapeutics [2]. In addition, it has become evident that the role of ARG characterization and tracing is essential to limit the rising dissemination of AMR in the clinical setting [3]. However, effective infection prevention control measures are frequently challenged by the extensive variety and complexity of ARG dissemination, which complicates epidemiological investigations that are commonly based on clonal transmission analysis. Multiple nested genetic levels must be accounted for, e.g., clones and mobile genetic elements (MGE) such as plasmids [4].

Reading this evidence

Use the full paper to check the study design, participant selection, comparator and outcome definitions before drawing a practical conclusion. An association does not by itself show cause and effect. A reported performance measure needs its denominator and uncertainty. A finding from a particular facility, sample or time period should retain that scope when it is discussed elsewhere.

This briefing makes the source accessible within the wider public health desk. It does not assess an individual patient or certify a product. When considering relevance to another health system, examine the original authors’ account of context and limitations, then seek local implementation evidence. The related reporting below provides other studies to read alongside this one; it is a topic connection, rather than a claim that their results are directly comparable.

© 2026 Connor A. J. Rossel, Lieke B. van Alphen, Edou R. Heddema, Paul H. M. Savelkoul. Excerpts reproduced under CC BY. Selection, formatting and contextual notes by HealthSignal. The researchers are the authors of the source study, not members of HealthSignal’s staff.

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HealthSignal’s publication desk curates source-based health analysis and attributed research briefings. Study authors and originating institutions are credited within each article. Preparation used AI assistance; source and licence checks do not constitute independent replication or clinical endorsement.

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