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, Sundius S,Kuske R,Brown SP. 2022. Defining the benefits of antibiotic resistance in commensals and the scope of resistance optimization. mBio. e01349-22
Varga JJ, Zhao CY, Davis JD, Hao Y, Farrell JM, Gurney JR, Voit E, Brown SP. Antibiotics drive expansion of rare pathogens in a chronic infection microbiome model. mSphere 7, e00318-22
Wollein Waldetoft, Brown SP. 2022. Evolving antibiotic spectrum. PNAS 119, e2214267119 (commentary).
Gurney J, Simonet C, Wollein Waldetoft K, Brown SP. 2022. Challenges and opportunities for cheat therapy in the control of bacterial infections. Natural Products Reports 39, 325-334 https://doi.org/10.1039/D1NP00053E
J Farrell, C Zhao, K Tarquinio, SP Brown. 2021. Causes and consequences of COVID-19 bacterial infections. Frontiers in Microbiology 12, 1911.
C Zhao, Y Hao, Y Wang, J Varga, A Stecenko, J Goldberg, SP Brown. 2021. Microbiome data enhances predictive models of lung function in people with cystic fibrosis. J Infectious Diseases 223, S246-S256.
J Gurney, SP Brown, O Kaltz, ME Hochberg. 2020. Steering phages to combat bacterial pathogens. Trends Microbiology 28, 85-94.
KW Waldetoft, J Gurney, J Lachance, PA Hoskisson, SP Brown. 2020, Evolving antibiotics against resistance: a potential platform for natural product development? mBio 10:e02946-19.
RC Allen, SP Brown. 2020. Modified antibiotic-adjuvant ratios can slow and steer the evolution of resistance: co-amoxiclav as a case study. mBio 10: e01831-19.
D McAdams, KW Waldetoft, C Tedijanto, M Lipsitch SP Brown. 2019. Resistance diagnostics as a public health tool to combat antibiotic resistance. PLOS Biology 17, 5 e3000250
K Wollein Waldetoft, SP Brown. 2017. Alternative therapeutics for self limiting infections: an indirect approach to the antibiotic resistance challenge. PLOS Biology 15, e2003533
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