What makes a superspreader? Genetic architecture, immune regulation and evolutionary constraints on pathogen acquisition and spread 

Funding: BBSRC; NERC Exploring the Frontiers Grant; Wellcome Trust PhD Program

Super-spreaders of infectious diseases are the most spectacular examples of host heterogeneity in pathogen transmission. What makes a superspreader? Despite their importance in driving the spread of infections in natural populations, we have a poor understanding of how host genetics contributes to variation in host traits that drive pathogen spread, and almost no understanding of the genetic basis of superspreading. We address two key questions: 1. How much of host variation in pathogen transmission is explained by their genetics? 2. What are the evolutionary constraints on extreme pathogen shedding phenotypes? Using a naturally-derived population of fruit flies, we quantify the phenotypic variation in locomotor activity, pathogen shedding, and host susceptibility following infection with the bacterial pathogen Pseudomonas aeruginosa. We then quantify how much of the phenotypic variance in these traits is explained by among-line genetic variance. As a second approach, we experimentally evolve super-shedders, starting from genetically variable outbred population, and then measure the direct and correlated responses to selection to identify evolutionary constraints on super-shedding individuals.

Key publications:

• Prakash A, Fenner F, Shit B, Salminen TS, Monteith KM, Khan I, et al. IMD-mediated innate immune priming increases Drosophila survival and reduces pathogen transmission. PLOS Pathogens. 2024;20: e1012308. doi:10.1371/journal.ppat.1012308

• Vale PF, Saad-Roy CM, Boots M. The ghost of infections past: Accounting for heterogeneity in individual infection history improves accuracy in epidemic forecasting. PLOS Biology. 2025;23: e3003311. doi:10.1371/journal.pbio.3003311

• Siva-Jothy, J.A. & Vale, P.F. 2021. Dissecting genetic and sex-specific sources of host heterogeneity in pathogen shedding and spread. PLOS Pathogens 17: e1009196.

• White, L.A., Siva-Jothy, J.A., Craft, M.E. & Vale, P.F. 2020. Genotype and sex-based host variation in behaviour and susceptibility drives population disease dynamics. Proceedings of the Royal Society B: Biological Sciences 287: 20201653.

• Vale, P.F., Choisy, M. & Little, T.J. 2013. Host nutrition alters the variance in parasite transmission potential. Biology Letters. 9: 20121145.

• Susi, H., Barrès, B., Vale, P.F. & Laine, A.-L. 2015a. Co-infection alters population dynamics of infectious disease. Nature Communications 6: 5975.

• Susi, H., Vale, P.F. & Laine, A.-L. 2015b. Host Genotype and Coinfection Modify the Relationship of within and between Host Transmission. Am. Nat. 186: 252–263.