Selective pressures during chronic infection drive microbial competition and cooperation

Selective pressures at the host–pathogen interface select for microbial adaptation and/or evolution. This figure depicts some of the possible stresses encountered by microbial pathogens while invading host tissues. For example, the innate immune system deploys phagocytes and neutrophils to target microbial pathogens at the site of infections. These cells can kill microbial cells by engulfing them and/or releasing antimicrobial molecules such as metal-binding proteins to sequester essential metals from pathogens, antimicrobial peptides such as LL-37, and reactive oxygen species. Pathogens like Staphylococcus aureus and Pseudomonas aeruginosa elicit physiological responses and/or evolve adaptations over the course of acute to chronic infection that allow them to circumvent these stresses and survive in spite of the presence of host offensive molecules. In this example, pathogen A is modeled after P. aeruginosa and pathogen B is modeled after S. aureus, but the disease progression may be applicable to other examples. Depicted here, initial infection of epithelial cells by S. aureus paves the way for opportunistic Gram-negatives such as P. aeruginosa. Microbial interactions of these species lead to formation of aminoglycosidic antibiotic resistant small colony variants (artistically depicted as smaller cells in the diagram) in S. aureus and might provide protection to P. aeruginosa from host immune insults. As the infection advances, the host–pathogen interface becomes populated by mutants that are selected for better survival such as mutants capable of dealing with host reactive oxygen species (such as pyomelanin producers depicted as releasing brown pigment) and mutants with increased biofilm formation to protect from phagocytosis and/or antimicrobial peptides such as LL-3