ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
This article is part of the Research TopicMolecular and Structural Strategies for Novel Antimicrobials and Host-Pathogen-Microbiota InteractionsView all 3 articles
Characterization of a novel composite ICE in Streptococcus agalactiae conferring resistance to macrolides [erm(TR)] and cadmium (cadA)
Provisionally accepted
- 1Shanghai Centre for Clinical Laboratory, Shanghai, China
- 2Fudan University Huashan Hospital Institute of Antibiotics, Shanghai, China
- 3Department of Molecular Diagnostic Innovation Technology, Shanghai Academy of Experimental Medicine, Shanghai, Shanghai, China
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Background: Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Methods: Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. Results: ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10−9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (<10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. Conclusions: This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification.
Keywords: antibiotic resistance genes, Antimicrobial susceptibility, Cadmium resistance, integrative and conjugative elements (ICEs), Streptococcus agalactiae
Received: 09 Dec 2025; Accepted: 12 Jan 2026.
Copyright: © 2026 Yi, Shi, Yin, Xu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xueliang Wang
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