Balancing Act: Dual targeting of PhoPQ and QseBC two-component systems in Edwardsiella tarda enhances attenuation but diminishes protective immunity.

Authors

Muhammad Nafees Ur Rehman, Yanrong Lin, Wei Feng, Mengqi Wang, Ijaz Khan, Lixia Fan, Xuesong Li, Nuo Yang, Guiying Guo, Jiping Zheng

Published in

Microbial pathogenesis. Pages 108764. Aug 12, 2026. Epub Aug 12, 2026.

Abstract

The PhoPQ and QseBC two-component systems (TCSs) regulate virulence and promote bacterial survival in vitro and in vivo, enabling competition in microenvironments or interactions with the host. However, their potential contributions to vaccine development remain uncharacterized in Edwardsiella tarda, a notorious pathogen that poses a substantial economic threat to the food and aquaculture industries. In this study, our data revealed that the deletion of either phoPQ or qseBC did not impair the growth and motility of E. tarda, except that PhoPQ inactivation led to growth retardation under magnesium (Mg²⁺)-limiting conditions (50 μM). Besides, the mutants of PhoPQ TCS enhanced sensitivities to polymyxin B, clindamycin, chloramphenicol, minocycline, oxytetracycline, and sulfafurazole, but QseBC TCS mutants showed the opposite trend. However, survival under oxidative and osmotic stress and biofilm formation capability were substantially reduced, especially in the double TCS mutant ΔqseBCΔphoP, which was the most severely impaired. Animal model results also demonstrated that the ΔqseBCΔphoP mutant was the most attenuated, with an LD₅₀ of 3.77 × 10⁶, followed by ΔphoP (6.7 × 10⁵), ΔqseB (7.9 × 10⁴), by comparing with the wild-type (WT) strain (7.55 × 10⁴). Differential gene expression analysis revealed significant downregulation of most tested virulence genes (including citC, flhC, flhD, fliP, luxS and mukF) in the ΔqseBCΔphoP strain. However, immune protection assay revealed a trade-off: ΔqseBCΔphoP exhibited lower relative percent survival (RPS: 29%) than ΔphoP (RPS: 53%), this was supported by elevated levels of specific antibodies in serum from fish vaccinated with ΔphoP, compared to those vaccinated with the strain ΔqseBCΔphoP. Furthermore, transcriptional profiling suggested that the enhanced protection conferred by the strain ΔphoP may stem from PhoPQ's global regulatory role in controlling LPS biosynthesis, metabolism, transport systems, transferase activity, and stress resistance mechanisms. Together, these findings demonstrate that dual TCS disruption synergistically reduces virulence factors (e.g., biofilm formation, stress tolerance) and pathogenicity but compromises immunogenicity. Importantly, PhoPQ shows greater potential as a vaccine target compared to QseBC for live attenuated vaccine (LAV) development against E. tarda.

PMID:
42586514
Bibliographic data and abstract were imported from PubMed on 13 Aug 2026.

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