Cooperative secretions facilitate host range expansion in bacteria

Abstract

The majority of emergent human pathogens are zoonotic in origin, that is, they can transmit to humans from other animals. Understanding the factors underlying the evolution of pathogen host range is therefore of critical importance in protecting human health. There are two main evolutionary routes to generalism: organisms can tolerate multiple environments or they can modify their environments to forms to which they are adapted. Here we use a combination of theory and a phylogenetic comparative analysis of 191 pathogenic bacterial species to show that bacteria use cooperative secretions that modify their environment to extend their host range and infect multiple host species. Our results suggest that cooperative secretions are key determinants of host range in bacteria, and that monitoring for the acquisition of secreted proteins by horizontal gene transfer can help predict emerging zoonoses.

Figure 1. Environment-modifying secretions as a route to host generalism.

We consider a scenario where pathogens can potentially transmit both within and among host species. Whereas specialists match their hosts closely (matching colours), generalists that infect multiple hosts are expected to have intermediate phenotypes (intermediate colour), meaning that they will lose to specialists during co-infections. While environmental modifiers may lose to specialists and generalists in the unmodified disease site, they can potentially invade by modifying this environment (transitions from red/blue to yellow) via the production of costly secretions (green triangles) that simplify the environment (loss of patterns). Specialists and classical generalists are not adapted to this modified environment, leading to their exclusion. While specialists and classical generalists are expected to show complex adaptations to their host(s) (complex shapes), environmental modifiers are expected to show simpler adaptations (simple shape), instead relying on secretions that modify and simplify their environment.

Figure 2. The phylogenetic distribution of zoonosis, genome size and secretome size.

The phylogenetic distribution of zoonotic status, secretome size and genome size is shown. Large genomes and secretomes are those greater than the median and small are less than or equal to the median. Note that the tree is ultrametricized for illustrative purposes only.

Figure 3. Bacterial secretions increase the ability of pathogens to infect multiple hosts.

(a) Standardized regression coefficients (multiplied by the standard deviation of the variable) estimated by the BPMM. Dots show the mode of the posterior distributions with lines indicating 95% CIs. Secretome size (yellow) has a positive effect on the probability that a pathogen is zoonotic, whereas genome size (blue) has a negative effect. (b) Data and BPMM predictions. Zoonoses are shown in red (n=121), whereas specialists are shown in blue (n=70). Background colours indicate the predictions of the BPMM.

Figure 4. Invading a population of specialists.

Plotted is the ‘basic reproductive number’ (number of new infections created per unit time when the pathogen is rare) of classical generalists (a) and environmental modifiers (b) when invading a population of specialists from our epidemiological model. The x and y axes are the rate at which infections are cleared (α) and the contact rate between host species (β_b), respectively. High reproductive numbers are red and low are blue. The yellow dashed line indicates where the reproductive number equals 1. At values above 1 the strain can invade. Our model predicts that a strain using environmental modification via secretions can invade a resident population of specialist strains under a wider range of conditions than a classical generalist strain can (smaller area above yellow dashed line in a than in b). Here s=1.5, g=1, b=1.25, c=0.25 and the within-host species contact rate, β_w=0.1. Environmental modifiers are better able to invade a population of specialists than classical generalists, despite identical within-host growth rates in single strain infections, as environmental modifiers alter the host environment to a form that specialists are not adapted to. This result holds whenever b>c.