Interplay of virulence factors shapes ecology and treatment outcomes in polymicrobial infections.

Polymicrobial infections, caused by a community of multiple micro-organisms, are often associated with increased infection severity and poorer patient outcomes. The design of improved antimicrobial treatment strategies for PMIs can be supported by an understanding of their ecological and evolutionary dynamics. Bacterial species present in polymicrobial infections can produce virulence factors to inhibit host immune responses, such as neutrophil recruitment and phagocytosis. The presence of virulence factors can indirectly affect other bacterial species acting as a type of host-mediated interspecies interaction. The aim of this study was to assess how bacterial virulence factors targeting neutrophil function influence ecology and treatment outcomes of PMIs. An agent-based model was constructed which describes a dual-species bacterial population in the presence of neutrophils and a bacteriostatic drug. Our analysis has revealed unforeseen dynamics of the interplay of multiple virulence factors acting as interspecies interaction. We found that the distribution of two phagocytosis-inhibiting virulence factors amongst species can impact whether they have a mutually protective effect for both species. The addition of a virulence factor inhibiting neutrophil recruitment was found to reduce the protective effect of phagocytosis-inhibiting virulence factors. Furthermore we demonstrate the importance of virulence strength of a species relative to other virulent species to determine the fate of a species. We conclude that virulence factors are an important driver of population dynamics in polymicrobial infections, and may be a relevant therapeutic target for treatment of polymicrobial infections.