Researchers realize the use of optical methods to control the movement of bacteria

The team of Jin Fan, a researcher at the Institute of Synthetic Biology, Shenzhen Academy of Advanced Technology, Chinese Academy of Sciences, and the team of Professor Liu Zhi, Huazhong University of Science and Technology, have collaborated to design an engineered strain based on Pseudomonas aeruginosa as a carrier, realizing the use of optical methods to control the movement of bacteria and Its host infectivity, related research results, titled Optogenetic Modification of Pseudomonas aeruginosa Enables Controllable Twitching Motility and Host Infection, were published on ACS Synthetic Biology.

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

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.
The expression levels of the three types of secretion system regulators ExsA, exotoxin protein ToxA, etc.
are jointly controlled to 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.

Based on this, Jinfan's research team introduced a photosensitive cAMP synthetase on the Pseudomonas aeruginosa chassis, and after a series of modifications, an engineered strain (named pactm) was constructed.

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.
This work provides a solution for the construction of a controllable infection experimental model.

In addition, the scientific researchers have realized the direction of the expansion of the bacterial population through the design of the macroscopic illumination mode, which provides convenience for the study of the interaction between microorganisms.

The research work is supported by the National Key Research and Development Program, the National Natural Science Foundation of China, and the Shenzhen Institute of Synthetic Biology Innovation.

Figure 1.
Design principle and application diagram of engineering strain pactm.
Figure 2.
Controlling the infectivity of bacteria on mice by light.
Source: Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences