One of the most basic and important questions posed by pathogens is why do they damage the very source of their livelihood, their hosts? In other words, why aren’t virulent pathogens that kill their hosts outcompeted by harmless commensals? The Brown lab pioneered the application of social evolution theory to this problem, highlighting the importance of the social dimension of virulence (both collective activity to damage a host, and shared consequences of damage) in order to understand the direction of selection on virulence. More recently we have developed and tested novel theory for scenarios where virulence results from ‘collateral damage’ of microbial competitive interactions, or due to generalist organisms simply getting into the wrong place and causing disease.
The lab couples basic enquiry with the challenge of addressing biomedical implications of our discoveries. We have outlined novel therapeutic strategies targeting social interactions, outlined their epidemiological and evolutionary risks and demonstrated that targeting microbial social interactions can deliver new therapeutics that are significantly more robust against evolution-induced failure than traditional antibiotic treatments.
Wollein Waldetoft K, Brown SP. In Press. Alternative therapeutics for self-limiting infections—An indirect approach to the antibiotic resistance challenge. PLOS Biology.
Cornforth D, Matthews A, Brown SP, Raymond B 2015. Bacterial cooperation causes systematic errors in pathogen risk assessment due to the failure of the Independent Action Hypothesis. PLOS Pathogens 10.1371/journal.ppat.1004775.
Allen R, Popat R, Diggle SP, Brown SP (2014) Targeting virulence: can we make evolution-proof drugs? Nature Reviews Microbiology 12, 300-308.
Ross-Gillespie A, Weigert M, Brown SP, Kummerli R (2014) Gallium-mediated siderophore quenching as an evolutionarily robust antibacterial treatment. Evolution, Medicine and Public Health 1, 18-29.
Vale P, Fenton A, Brown SP (2014) Limiting Damage during Infection: Lessons from Infection Tolerance for Novel Therapeutics. PLOS Biology 12, e1001769.
- Nazzi et al. 2012. Synergistic Parasite-Pathogen Interactions Mediated by Host Immunity Can Drive the Collapse of Honeybee Colonies. PLoS Pathogens 8 (6), e1002735
Brown SP, Cornforth DM, Mideo N (2012) Evolution of virulence in opportunistic pathogens: generalism, plasticity and control. Trends in Microbiology 20, 336-342
Lysenko ES, Lijek RS, Brown SP & Weiser JN. 2010. Within-host competition drives selection for the capsule virulence determinant of Streptococcus pneumoniae. Current Biology 20, 1222-1226.
Brown SP, West SA, Diggle SP, Griffin AS. 2009. Social evolution in microorganisms and a trojan horse approach to medical intervention strategies. Phil. Trans. Roy. Soc. Lond. B. 364, 3157-68
Brown SP, Inglis R, Taddei F. 2009. Evolutionary ecology of microbial wars: within-host competition and (incidental) virulence. Evolutionary Applications 2, 32-39.
Brown SP, Le Chat L & Taddei F 2008. Evolution of virulence: triggering host inflammation allows invading pathogens to exclude competitors. Ecology Letters 11, 44-51
Brown SP, Hochberg M.E. & Grenfell B.T. 2002. Does multiple infection select for increased virulence?Trends Microbiol. 10, 401-405