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[Response Mechanism of the VBNC Dormant State of Escherichia coli Induced by Typical Antiviral Agents].

Created on 27 Oct 2026

Authors

Tong Sun, Jun-Qi Yang, Yi-Wei Cai, Gui-Ying Li, Tai-Cheng An

Published in

Huan jing ke xue= Huanjing kexue. Volume 47. Issue 10. Pages 7354-7362. Oct 15, 2026.

Abstract

During the COVID-19 pandemic, the extensive use of antiviral agents has led to the release and accumulation of many incompletely metabolized agents in the environment, further affecting indigenous microbial communities. Under the adverse environmental pressures, microorganisms may enter dormant states, such as the viable but nonculturable (VBNC) state, and exhibit strong stress-resistant phenotypes. However, there is still a lack of systematic reports on whether antiviral agents can induce microorganisms to enter the VBNC state. Therefore, typical antiviral agents (Ritonavir and Lopinavir) were used to expose Escherichia coli (E. coli) to investigate the effects of antiviral agents on the culturability of bacteria, the formation of the VBNC state, cell morphological structure, and growth characteristics and to elucidate the underlying molecular regulatory mechanisms. The results showed that the inhibition of E. coli culturability and the induction of the VBNC state by Ritonavir initially increased and then decreased with increasing concentration. The inhibitory effect peaked at a concentration of 128 mg·L-1, with a 99.23% reduction in culturable bacterial counts when a proportion of VBNC bacteria reached 73%. In contrast, Lopinavir significantly inhibited the culturability of E. coli only at a high concentration (256 mg·L-1), with a 97.2% reduction in the number of culturable bacteria and a proportion of VBNC bacteria reaching 77%. Simultaneously, analyses using plate culture counting, flow cytometry, growth curve determination, and SEM imaging revealed that the VBNC bacteria induced by Ritonavir and Lopinavir exhibited growth arrest and decreased cell volume. Mechanistic studies demonstrated that bacteria exposed to Ritonavir and Lopinavir entered the VBNC state through the accumulation of intracellular reactive oxygen species (ROS) and dynamic regulation of the antioxidant system. Exploring the stress effects of typical antiviral agents on bacteria and the induction mechanisms of VBNC state helps to clarify the interaction patterns between agents and microorganisms. It also provides experimental evidence for assessing the environmental ecological risks of antiviral agents.

PMID:
42935435
Bibliographic data and abstract were imported from PubMed on 27 Oct 2026.

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