Selective pressures during chronic infection drive microbial competition and cooperation

Abstract

Chronic infections often contain complex mixtures of pathogenic and commensal microorganisms ranging from aerobic and anaerobic bacteria to fungi and viruses. The microbial communities present in infected tissues are not passively co-existing but rather actively interacting with each other via a spectrum of competitive and/or cooperative mechanisms. Competition versus cooperation in these microbial interactions can be driven by both the composition of the microbial community as well as the presence of host defense strategies. These interactions are typically mediated via the production of secreted molecules. In this review, we will explore the possibility that microorganisms competing for nutrients at the host-pathogen interface can evolve seemingly cooperative mechanisms by controlling the production of subsets of secreted virulence factors. We will also address interspecies versus intraspecies utilization of community resources and discuss the impact that this phenomenon might have on co-evolution at the host-pathogen interface.

Keywords: Evolution; Microbiome; Pathogens.

Fig. 1

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-37

Fig. 2

Competitive interactions versus cooperative polymicrobial interactions at the host–pathogen interface. This figure compares the potential costs and/or benefits experienced by microbial cells when they are interacting competitively versus cooperatively with other species inside a host. a Microbial cells exhibiting a competitive lifestyle must not only expend biosynthetic costs for production of competitive molecules to combat surrounding pathogens, but they must also independently deal with the onslaught of host-associated harsh conditions such as immune cells, antibiotic treatment, and nutrient limitation. b Microbial cells exhibiting a more cooperative lifestyle do not expend energy on antimicrobials and therefore may have more energy to expend on molecules designed to combat the host-associated harsh conditions. Additionally, they might also reap the benefits of the secreted molecules produced by their neighboring microbes to achieve greater levels of survival at the host–pathogen interface