Pathogen Diversity and Hidden Regimes of Apparent Competition

Abstract

Competition through cross-reacting host immune responses, a form of apparent competition, is a major driver of pathogen evolution and diversity. Most models of pathogens have focused on intraspecific interactions to explain observed patterns. Two recent experiments suggested that Haemophilus influenzae, a common nasopharyngeal colonizer of humans, might alter the immune environment in a way that favors otherwise less fit serotypes of another common pathogen, pneumococcus. Using a computational model, we demonstrate that H. influenzae, if it consistently raises the fitness of the less fit serotypes, can strongly promote pneumococcal diversity. However, the effects of H. influenzae are so sensitive to the prevalence of H. influenzae that this species is unlikely to be the main driver of serotype coexistence. Interactions that significantly affect diversity could furthermore be extremely difficult to detect through co-occurrence analysis alone. These results suggest that small differences in strains’ adaptations to different immunological regimes, which are shaped by coinfections with other pathogens, can have dramatic effects on strain dynamics and patterns of phenotypic variation. Studies of microbial communities might therefore benefit from the use of varied approaches to infer the presence of indirect interactions.

Host and parasite diversity jointly control disease risk in complex communities

“…Antagonistic effects among parasites could result from competition for a shared resource (e.g., space or host cells) or interactions mediated through host immunity (7). Based on the differences in infection sites among the parasites included here and their low metabolic demands within second intermediate hosts, cross-reactive immunity is perhaps the most probable mechanism, consistent with a growing emphasis on the role of host immunity in determining coinfection outcomes (31,(33)(34)(35)(36). That host diversity generally had stronger inhibitory effects on parasite loads than did parasite diversity may stem from the greater potential for low-competence hosts to function as population sinks for invading parasites, whereas immune-mediated competition associated with coinfection acts primarily to weaken persistence of parasites that have already colonized (2,37).…”

Density, Serotype Diversity, and Fitness ofStreptococcus pneumoniaein Upper Respiratory Tract Cocolonization With NontypeableHaemophilus influenzae

“…CD4 + T-cell responses mediate immunity to pneumococcal and NTHi carriage [36][37][38], and their diminishing prominence among older children may underlie the disappearance of species associations. In contrast, associations mediated by direct bacterial interactions would be expected to be age-independent, although acquired anticapsular immunity against previously carried serotypes may confound associations in older children [26,39]. Pneumococcal serotypes prevalent in carriage with lower disease potential are disproportionately represented in polymicrobial pneumococci-NTHi OM [5].…”

“…Considering the subset of visits where children carried pneumococci in the nasopharynx, we constructed logistic regression models with generalized estimating equations to determine ORs and aORs of NTHi colonization associated with measures of pneumococcal serotype fitness and virulence (Table 1). This approach prevents confounding by fitness factors that also predict variation in pneumococcal serotype prevalence [26]. Models controlled for the same covariates included in the density analyses and were again stratified by children's age (2-18 or 19-30 months) and NTHi colonization site, with NTHi-negative child-visits providing the comparator group.…”

Interactions Within Susceptible Hosts Drive Establishment of Genetically Distinct Variants of an Insect-Borne Pathogen

“…Interactions between pathogens in hosts can lead to resource competition, in which pathogens compete for a limiting resource such as nutrients (Lacroix et al 2014). Alternatively apparent competition between two pathogens, in which the defense response of the host is a shared enemy of multiple pathogens (Cobey and Lipsitch 2013), may determine the outcome of mixed infections.…”