Competitive exclusion strengthens selection for transmissibility and increases the benefit of recombination for within-host adaptation

Abstract

10Pathogens experience selection at multiple scales, given the need to transmit between hosts 11 and replicate within them. This presents the challenge of cross-scale selective conflict when 12 adaptations to one scale compromise fitness at another, such as mutations that improve 13 transmissibility but make individuals less competitive within hosts. Selection operates differently 14 at these scales, with tight transmission bottlenecks subjecting pathogen populations to genetic drift, 15 and large population sizes within hosts enabling efficient selection for beneficial mutations.16 Compounding the reduction in diversity by transmission bottlenecks is the occupant-intruder 17 competitive strategy exhibited by some pathogens, where the first variant to colonize a host 18 prevents later arriving variants from contributing to infection, preventing immigration and turning 19 transmission into a "founder takes all" contest. Here, we used multiple modeling approaches to 20 examine how this behavior affects the efficiency of selection for both transmissibility and within-21 host fitness. We find that in the face of a trade-off, selection for transmissibility is maximized 22 under a tight transmission bottleneck that minimizes within-host competition during colonization. 23 While mutations with increased within-host fitness are favored during within-host replication, an 24 occupant-intruder strategy prevents these mutants from displacing established residents and 25 propagating across the host population, leading to their extinction if they are insufficiently 26 transmissible. Finally, a model of competition on the scale of the host population revealed that 27 competitive exclusion limits the propagation of mutations with improved within-host fitness, 28 unless resident populations can incorporate alleles from intruding variants by recombination. Thus, 29 competitive exclusion may facilitate the improvement and maintenance of pathogen 30 transmissibility, with directional recombination allowing resident populations to mitigate the 31 potential loss of within-host fitness imposed by this occupant-intruder strategy. 32 Author Summary 33 Transmission is a defining feature of infectious diseases, and so a better understanding of how 34 transmissibility evolves is important for improving disease surveillance and prevention. Successful 35 transmission is often achieved by a small number of individuals which, after establishing residency 36 in a host, may prevent newcomers from participating in infection. Here, we use modeling to 37 examine how competitive exclusion of challengers by resident populations affects the balance 38 between within-host competitive ability and transmissibility. We find that competitive exclusion 39 strengthens selection for transmissibility by disproportionately benefitting the first variant to 40 colonize a host and preventing mutants that may be more competitive but less transmissible from 41 displacing established residents. Competitive exclusion also limits the propagation of mutants that 42 impro...

Pneumococcal Colonization and Virulence Factors Identified Via Experimental Evolution in Infection Models

“…2016 )—was bypassed by manual transfer of pneumococci between animals. The need to balance attachment and colonization with shedding and transmission is likely a major determining factor in the trajectory of pneumococcal evolution and the trade-off between transmissibility and within-host fitness has been recently highlighted ( Jacobs and Weiser 2020 ). The authors outline the role played by competitive exclusion in restricting population diversity, whereby the first variant to colonize prevents later arrivals from doing so.…”