posted on 2021-06-02, 15:04authored byXinyi Cheng, Lu Pu, Shengwei Fu, Aiguo Xia, Shuqiang Huang, Lei Ni, Xiaochen Xing, Shuai Yang, Fan Jin
Bacterial pathogens operate by tightly
controlling the pathogenicity
to facilitate invasion and survival in host. While small molecule
inducers can be designed to modulate pathogenicity to perform studies
of pathogen–host interaction, these approaches, due to the
diffusion property of chemicals, may have unintended, or pleiotropic
effects that can impose limitations on their use. By contrast, light
provides superior spatial and temporal resolution. Here, using optogenetics
we reengineered GacS of the opportunistic pathogen Pseudomonas
aeruginosa, signal transduction protein of the global regulatory
Gac/Rsm cascade which is of central importance for the regulation
of infection factors. The resultant protein (termed YGS24) displayed
significant light-dependent activity of GacS kinases in Pseudomonas
aeruginosa. When introduced in the Caenorhabditis
elegans host systems, YGS24 stimulated the pathogenicity
of the Pseudomonas aeruginosa strain PAO1 in a brain–heart
infusion and of another strain, PA14, in slow killing media progressively
upon blue-light exposure. This optogenetic system provides an accessible
way to spatiotemporally control bacterial pathogenicity in defined
hosts, even specific tissues, to develop new pathogenesis systems,
which may in turn expedite development of innovative therapeutics.