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. 2025 Sep:206:107797.
doi: 10.1016/j.micpath.2025.107797. Epub 2025 Jun 9.

Effects of Hxc-T2SS on the phenotypic features and virulence of Pseudomonas aeruginosa PAO1

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Effects of Hxc-T2SS on the phenotypic features and virulence of Pseudomonas aeruginosa PAO1

Xiaojuan Tan et al. Microb Pathog. 2025 Sep.

Abstract

Pseudomonas aeruginosa possesses two subtypes of the type II secretion system (T2SS), Xcp and Hxc. Xcp-T2SS has been identified as responsible for the secretion of toxins and enzymes, which contribute to pathogenicity. The role of the Hxc system in the pathogenicity of P. aeruginosa, however, remains unclear, though it is known to secrete the low molecular weight alkaline phosphatase LapA under phosphate-depleted stress. In this study, the Hxc system was disrupted by creating an hxcR mutant in P. aeruginosa PAO1. The virulence factors of this mutant were evaluated and compared with those of the wild-type PAO1 strain under phosphate-depleted conditions. The results indicated that the hxcR mutation led to a decrease in rhamnolipid and pyocyanin production by regulating phosphate acquisition and the PhoR/PhoB two-component regulatory system. Moreover, biofilm formation in vitro was enhanced due to an increase in intracellular c-di-GMP levels under phosphate-depleted conditions. However, the deletion of the hxcR gene significantly reduced biofilm formation in ex vivo porcine skin explants, a model for chronic wounds. Furthermore, inactivation of hxcR decreased the pathogenicity of PAO1 in C. elegans during both fast-kill and slow-kill assays under phosphate-depleted conditions. These results suggest that targeting the Hxc system could be a potential strategy to control biofilm formation and reduce virulence in nonhealing infected wounds, where P. aeruginosa is a persistent issue.

Keywords: Biofilm; Chronic wound infection; Hxc-T2SS; Pseudomonas aeruginosa; Virulence factors.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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