From Point Mutation to Gene Loss: A Shift in Focus
Our journey began with an intriguing observation: the pandemic clone of Vibrio parahaemolyticus, the leading cause of seafood-associated infections globally, had undergone successive “waves” of lineage replacement over the past two decades, with the “Wave 4” variant ultimately rising to dominance.
Initially, we focused on point mutations in classical virulence genes, although we had noted gene loss in the putrescine metabolism pathway. Early virulence-related experiments yielded mixed results. Then, by chance, we came across a paper on polyamine (putrescine) metabolism and biofilm formation in Pseudomonas aeruginosa (https://doi.org/10.1128/JB.00297-21).
Given the importance of biofilms in bacterial survival and pathogenesis, we shifted our attention to this previously overlooked gene loss. We ultimately found that it was also associated with enhanced biofilm formation in V. parahaemolyticus and, unexpectedly, linked to host colonization-related traits, including increased cell adhesion and intestinal colonization, as well as reduced virulence—these novel findings!
First Time at the Bench: A Personal Milestone
Trained in computational genomics, this project marked my first foray into the world of wet-lab biology. The extent of experimental validation required was far beyond my comfort zone, but I was fortunate to work with a team of generous and skilled collaborators. Each contributed critically to different aspects of the experimental work—mutant construction (e.g., Sarah L. Svensson), phenotype assays (e.g., Hongling Qiu, Chengpei Ni, Zhizhou Jia), and colonization studies (e.g. Song Gao, Huiqi Wen). It was a humbling and immensely rewarding learning experience. My deepest thanks to all of you!
A Cross-Species Hypothesis Takes Shape
Because the biofilm-enhancing effects of polyamines were originally reported in P. aeruginosa, we hypothesize that this might represent a more generalizable mechanism. Returning to bioinformatics, I conducted large-scale genomic screening and identified putrescine gene loss in multiple species, including Vibrio cholerae and Escherichia coli.
By a stroke of luck, our collaborator Yanjie Chao (many thanks!) had these strains readily available in his lab, enabling us to test this hypothesis across species. Remarkably, the results confirmed our expectations—the same gene loss conferred similar phenotypic effects across species, supporting a case of convergent evolution in distinct bacterial pathogens.
Toward a General Model of Pathogen Evolution
This study offered me a glimpse into what may be a recurring evolutionary principle: the trade-off between virulence and transmission. In V. parahaemolyticus, gene loss led to reduced virulence but enhanced human transmission—traits that support long-term transmission and evolutionary success. Similar patterns have been observed in other pathogens. For instance, newer variants of SARS-CoV-2 exhibit reduced severity alongside increased transmissibility. In Yersinia pestis, the causative agent of plague, reduced virulence was also documented during historical pandemics (https://doi.org/10.1126/science.adt3880). Moreover, we identified signatures of attenuated virulence evolution in both Vibrio cholerae (https://doi.org/10.1371/journal.pntd.0008046) and Bordetella pertussis (https://doi.org/10.1016/j.cmi.2024.08.016)—findings that may spark broader discussions on the adaptive logic of pathogenicity.
End
Gene loss, once thought to be merely degenerative, may, in fact, be one of nature’s most elegant strategies for adaptation.