Pseudomonas aeruginosa polymicrobial interactions during lung infection

Abstract

Chronic infections often contain complex polymicrobial communities that are recalcitrant to antibiotic treatment. The pathogens associated with these infectious communities are often studied in pure culture for their ability to cause disease. However, recent studies have begun to focus on the role of polymicrobial interactions in disease outcomes. Pseudomonas aeruginosa can colonize patients with chronic lung diseases for years and sometimes even decades. During these prolonged infections, P. aeruginosa encounters a plethora of other microbes including bacteria, fungi, and viruses. The interactions between these microbes can vary greatly, ranging from antagonistic to synergistic depending on specific host and microbe-associated contexts. These additional layers of complexity associated with chronic P. aeruginosa infections must be considered in future studies in order to fully understand the physiology of infection. Such studies focusing on the entire infectious community rather than individual species may ultimately lead to more effective therapeutic design for persistent polymicrobial infections.

Figure 1.. Microbial interactions experienced by P. aeruginosa in the lungs.

The lungs are colonized by diverse bacterial, fungal, and viral taxa. The interactions of P. aeruginosa with the other microbes inhabiting the lungs can be both cooperative and competitive in nature. In particular, this review focuses on (1A) bacterial interactions such as intraspecies interactions between sublineages of P. aeruginosa as well as in interspecies interactions with S. aureus, (1B) interkingdom interactions with fungi such as C. albicans and A. fumigatus, and (1C) interactions with viruses such as RSV and bacteriophages.

Figure 2.. Intra- and interspecies bacterial interactions exhibited by P. aeruginosa in the lungs.

In the host tissues, P. aeruginosa cells interact with neighboring bacterial cells, competitively or cooperatively, to establish persistent infections. Intraspecies interactions between P. aeruginosa sublineages and strains can be cooperative (2A) such as when different P. aeruginosa isolates like the methionine auxotroph depicted as green cells and the arginine auxotroph depicted as brown cells share the production of biosynthetic molecules or competitive (2B) as certain strains can dominate over others via the production of pyocins. Similarly interspecies interactions with the common co-infecting pathogen S. aureus can be competitive (2C) as P. aeruginosa can produce antimicrobials that not only intoxicate S. aureus but also increase susceptibility to certain antimicrobial agents or synergistic (2D) via P. aeruginosa’s exploitation of S. aureus’s anti-host factors, a phenomenon that may in turn select for P. aeruginosa’s repression of anti-staphylococcal molecules in the presence of host proteins like calprotectin and serum protein albumin.

Figure 3.. Interactions between P. aeruginosa and other microbial inhabitants of the cystic fibrosis lungs.

In addition to the bacterial interactions of P. aeruginosa, recent studies have also shown its interaction with fungus and viruses. This figure highlights some of these interactions in the context of synergism or antagonism. Phenazines secreted by P. aeruginosa can help in ethanol production by C. albicans which in turn increases production of Pel polysaccharide in the former (3A) resulting in a synergistic interaction. On the contrary, P. aeruginosa can interact competitively with other fungal species such as A. fumigatus via production of reactive oxygen and nitrogen species (3B). Figures 3C and 3D represents P. aeruginosa’s interaction with viruses which are critical but understudied. Viruses such as Respiratory syncytial viruses (RSV) can impair host nutritional immunity making iron bioavailable for P. aeruginosa and helping it to switch from planktonic to biofilm lifestyle (3C). Other viruses such as phages can also help P. aeruginosa survive the hostile lung environment by introducing mutations that can lead to emergence of divergent strains well adapted to the CF lungs (3D).