From liking watermelon to liking a watermelon pathogen

This story is about how we diverted research from working on human pathogens to a plant pathogen and discovered a very cool and powerful T6SS that can penetrate into gram-positive cells.

I have always liked watermelon ever since I was a kid but I had never thought about liking a watermelon pathogen this much. Now I have changed. 

My lab has been studying the type VI protein secretion system (T6SS) that is one of the most important tools for gram-negative bacteria to interact with other bacteria and eukaryotic cells in the environment or in the host, contributing to bacterial pathogenesis and environmental adaptation. Simply put, it's super cool. The T6SS resembles a contractile spear-like weapon that is assembled in the cell.  Upon contraction, the spear is thrust out to directly penetrate a neighbouring gram-negative bacterium's cell wall and membranes and deliver toxic proteins to the cytoplasm. And this is done by physical force. The outer-sheath of T6SS (~1 micrometer long) spins at a speed of ~300,000 rpm, releasing the energy of about 1,000 ATP in 2 milliseconds, which propels a stiff spear-like inner tube directly into a neighbouring cell's cytoplasm. However, gram-positive cells seem to be impenetrable for such cytosol-to-cytosol delivery for a long time despite several reports on the various effects of T6SS on gram-positive cells' physiology. 

Acidovorax citrulli (AC) is a gram-negative plant pathogen that causes bacterial fruit blotch disease in a variety of melon crops. Having always worked on human pathogens, I didn't know about AC until Dr. Yumin Kan joined my lab as a postdoctoral fellow in May 2020. Yumin had experience working on the type 3 secretion system in AC during her Ph.D. Due to my interest in devouring sweet and juicy watermelon, I want to keep watermelon healthy. I asked her to see how AC interacts with plant-associated bacteria. Surprisingly, almost all bacteria she initially tested were killed by AC. We eventually found that AC could use its T6SS to kill gram-negative, gram-positive, fungi. What a killer!  

My Ph.D. student Tong-Tong Pei had just finished working on an Rhs-family effector at the time. She found that AC contains multiple Rhs-family effector proteins. She, Yumin, and others in the lab quickly worked as a team on this project. We found that an Rhs-family nuclease effector RhsB is crucial for killing gram-positive Bacillus subtilis, providing strong evidence for T6SS penetration into the cytosol of B. subtilis cells. We first deposited our main findings in bioRxiv in May 2021 (  Around the same time, I joined the editorial board of a new microbiology journal mLife (  I believe this is going to be a great platform for microbiologists to share their exciting stories. And we feel very happy to publish our expanded story in the inaugural issue of mLife (  

In comparison with the numerous studies on the T6SS in human pathogens, there are fewer studies on T6SS functions in plant-associated bacteria. Our story demonstrates that those plant-associated bacteria have many exciting and important secrets to be unearthed. Their superb microbe-killing tools may help us develop new and green strategies for agriculture applications and for improving human health.    

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