“Within-host priority effects systematically alter pathogen coexistence”

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Patrick A. Clay, Kailash Dhir, Meghan A. Duffy, and Volker H. W. Rudolf (Feb 2019)

The DOI will be https://dx.doi.org/10.1086/701126

Within-host priority effects foster pathogen coexistence if pathogens benefit from arriving second in coinfections

The order in which pathogens infect hosts determines how they interact, and whether they can coexist

Many organisms are infected with multiple pathogen species at the same time. For instance, many humans are infected with both gut helminths and HIV, malaria, or tuberculosis. These “coinfections” can alter host health, maintain biodiversity, and drive pathogen evolution. However, not all pathogens can coexist within a host population. This is because they are constantly competing for hosts and the resources that hosts contain. One factor that defines how pathogens compete with one another is the order in which they infect hosts. Sometimes, infecting a host first gives a pathogen a competitive advantage over later arriving organisms. Sometimes, infecting an already infected host gives a pathogen an advantage. These “within-host priority effects” are common, but we don’t know how they scale up to alter disease patterns in host populations.

Here, Patrick Clay and Volker Rudolf from Rice University, and Kailash Dhir and Meghan Duffy from the University of Michigan teamed up to test whether within-host priority effects can alter pathogen coexistence, using a model system of coinfected zooplankton. In this system, pathogens can be repressed by coinfection if they arrive first in coinfected hosts, and facilitated by coinfection if they arrive second in coinfected hosts. This increases the probability that multiple pathogens can infect populations of zooplankton at once. Their results indicate that within-host priority effects can scale up to alter large scale disease patterns, and should be taken into account when trying to understand and predict multi-pathogen dynamics.


Abstract

Coinfection of host populations alters pathogen prevalence, host mortality, and pathogen evolution. Because pathogens compete for limiting resources, whether multiple pathogens can coexist in a host population can depend on their within-host interactions which, in turn, can depend on the order in which pathogens infect hosts (within-host priority effects). However, the consequences of within-host priority effects for pathogen coexistence have not been tested. Using laboratory studies with a coinfected zooplankton system, we found that pathogens had increased fitness in coinfected hosts when they were the second pathogen to infect a host, compared to when they were the first pathogen to infect a host. With these results, we parameterized a pathogen coexistence model with priority effects, finding that pathogen coexistence (1) decreased when priority effects increased the fitness of the first pathogen to arrive in coinfected hosts, and (2) increased when priority effects increased the fitness of the second pathogen to arrive in coinfected hosts. We also identified the natural conditions under which we expect within-host priority effects to foster coexistence in our system. These outcomes were the result of positive or negative frequency dependence created by feedback loops between pathogen prevalence and infection order in coinfected hosts. This suggests that priority effects can systematically alter conditions for pathogen coexistence in host populations, thereby changing pathogen community structure and potentially altering host mortality and pathogen evolution via emergent processes.