Pneumococcus and the stress-gradient hypothesis: a trade-off links $R_0$ and susceptibility to co-colonization across countries

TL;DR

This study links pneumococcal transmission intensity with co-colonization susceptibility across countries, revealing a trade-off consistent with the stress-gradient hypothesis, and introduces a simple model for bacterial strain coexistence.

Contribution

It provides a global analysis of pneumococcus co-colonization patterns using a mathematical model, highlighting a conserved ratio linking transmission and co-colonization susceptibility.

Findings

Negative correlation between $R_0$ and $k$ across settings

Serotype composition remains consistent globally

A conserved ratio $rac{1}{(R_0-1)k}$ links transmission and co-colonization

Abstract

Modern molecular technologies have revolutionized our understanding of bacterial epidemiology, but reported data across different settings remain under-integrated in common theoretical frameworks. Pneumococcus serotype co-colonization, caused by the polymorphic bacteria Streptococcus pneumoniae, has been increasingly investigated in recent years. While the global genomic diversity and serotype distribution of S. pneumoniae are well-characterized, there is limited information on how co-colonization patterns vary globally, critical for understanding bacterial evolution and dynamics. Gathering a rich dataset of cross-sectional pneumococcal colonization studies in the literature, we quantified patterns of transmission intensity and co-colonization prevalence in children populations across 17 geographic locations. Fitting these data to an SIS model with co-colonization under the assumption of similarity among interacting strains, our analysis reveals strong patterns of negative co-variation between transmission intensity ($R_0$) and susceptibility to co-colonization ($k$). In support of the stress-gradient hypothesis in ecology (SGH), pneumococcus serotypes appear to compete more in high-transmission settings and less in low-transmission settings, a trade-off which ultimately leads to a conserved ratio of single to co-colonization $\mu=1/(R_0-1)k$. Within our mathematical model, such conservation suggests preservation of 'stability-diversity-complexity' regimes in multi-strain coexistence. We find no major study differences in serotype composition, pointing to underlying adaptation of the same set of serotypes across environments. Our work highlights that understanding pneumococcus transmission patterns from global epidemiological data can benefit from simple analytical approaches that account for quasi-neutrality among strains, co-colonization, as well as variable environmental adaptation.