ACS Synthetic Biology: Shenzhen Advanced Institute realized the use of optical methods to control the movement of bacteria

Recently, the Jinfan team from the Institute of Synthesis, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences and Liu Zhi’s team from Huazhong University of Science and Technology have collaborated to design an engineered strain based on Pseudomonas aeruginosa as a carrier, and realized the use of optical methods to control the bacterial movement behavior and its host The appeal of the above and related research results were published in the international academic journal ACS Synthetic Biology with the title "Optogenetic Modification of Pseudomonas aeruginosa Enables Controllable Twitching Motility and Host Infection".

Xia Aiguo, a postdoctoral fellow from Shenzhen Institute of Advanced Technology, is the first author of the article, and assistant researcher Ni Lei, researcher Jin Fan, and Professor Liu Zhi from Huazhong University of Science and Technology are co-corresponding authors.

Cyclic Adenosine Phosphate (cAMP) is an important secondary messenger molecule in Pseudomonas aeruginosa, which plays a key role in regulating bacterial carbon source metabolism, assembly and synthesis of type IV fimbriae, and bacterial virulence.

When cAMP regulates a certain physiological function of bacteria, it usually simultaneously regulates the expression of multiple component proteins that affect this physiological function, so as to ensure the transition of this physiological state.

For example, cAMP-Vfr realizes the regulation of bacterial rubbing movement by co-controlling the expression levels of the four-type fimbriae structural protein PilA, the motor protein PilT, PilB, and the transcriptional regulatory protein PilR.
cAMP-Vfr also regulates the bacterial rubbing movement.
The co-control of the expression levels of the endogenous secretory system regulator ExsA and the exotoxin protein ToxA can regulate the virulence of bacteria.

The transformation of bacterial physiological functions such as the above-mentioned rubbing movement and bacterial virulence are usually not easily accomplished by controlling the expression of a single or a small amount of genes.

Figure 1: Design principle and application diagram of the engineered strain pactm Based on the above understanding, the Jinfan research team introduced photosensitivity cAMP synthetase on the Pseudomonas aeruginosa chassis, and after a series of modifications, an engineered strain was constructed (Named pactm).

The engineered strain can reversibly change its own rubbing activity and its ability to infect the host in response to blue light irradiation.

Under blue light irradiation, the expression of pactm's cAMP-responsive promoter increased by 15 times, and the activity of rubbing movement increased by 8 times.

The nude mouse subcutaneous infection model showed that blue light irradiation increased the skin damage area of ​​mice caused by pactm infection by 14 times, so this work provides a solution for the construction of a controlled infection experimental model.

In addition, the author successfully realized the direction of the expansion of bacterial populations through the design of the macroscopic illumination mode, which provided convenience for the study of the interaction between microorganisms.

Figure 2: Controlling the infectivity of bacteria in mice through light.
The research was supported by the major research and development program of the Ministry of Science and Technology, the National Natural Science Foundation of China, and the Shenzhen Institute of Synthetic Biology Innovation.Paper link: https://doi.
org/10.
1021/acssynbio.
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