The effects of spatial structure, frequency dependence and resistance evolution on the dynamics of toxin-mediated microbial invasions

Recent evidence suggests that interference competition between bacteria shapes the distribution of the opportunistic pathogen Staphylococcus aureus in the lower nasal airway of humans, either by preventing colonization or by driving displacement. This competition within the nasal microbial community would add to known host factors that affect colonization. We tested the role of toxin-mediated interference competition in both structured and unstructured environments, by culturing S. aureus with toxin-producing or nonproducing Staphylococcus epidermidis nasal isolates. Toxin-producing S. epidermidis invaded S. aureus populations more successfully than nonproducers, and invasion was promoted by spatial structure. Complete displacement of S. aureus was prevented by the evolution of toxin resistance. Conversely, toxin-producing S. epidermidis restricted S. aureus invasion. Invasion of toxin-producing S. epidermidis populations by S. aureus resulted from the evolution of toxin resistance, which was favoured by high initial frequency and low spatial structure. Enhanced toxin production also evolved in some invading populations of S. epidermidis. Toxin production therefore promoted invasion by, and constrained invasion into, populations of producers. Spatial structure enhanced both of these invasion effects. Our findings suggest that manipulation of the nasal microbial community could be used to limit colonization by S. aureus, which might limit transmission and infection rates.