Chronic pulmonary pseudomonal infection in patients with cystic fibrosis: A model for early phase symbiotic evolution

Abstract

Gain of “antimicrobial resistance” and “adaptive virulence” has been the dominant view of Pseudomonas aeruginosa (Pa) in cystic fibrosis (CF) in the progressively damaged host airway over the course of this chronic infection. However, the pathogenic effects of CF airway-adapted Pa strains are notably reduced. We propose that CF Pa and other bacterial cohabitants undergo host adaptation which resembles the changes found in bacterial symbionts in animal hosts. Development of clonally selected and intraspecific isogenic Pa strains which display divergent colony morphology, growth rate, auxotrophy, and antibiotic susceptibility in vitro suggests an adaptive sequence of infective exploitation-parasitism-symbiotic evolution driven by host defenses. Most importantly, the emergence of CF pseudomonal auxotrophy is frequently associated with a few specific amino acids. The selective retention or loss of specific amino acid biosynthesis in CF-adapted Pa reflects bacterium-host symbiosis and coevolution during chronic infection, not nutrient availability. This principle also argues against the long-standing concept of dietary availability leading to evolution of essential amino acid requirements in humans. A novel model of pseudomonal adaptation through multicellular bacterial syntrophy is proposed to explain early events in bacterial gene decay and decreased (not increased) virulence due to symbiotic response to host defense.

• Auxotrophy
• isogenic
• multicellular
• symbiosis
• syntrophy

Acknowledgements

I would like to thank Dr. Michael A. McNutt (Peking University School of Medicine, Beijing, PRC) for our reciprocal interests in learning English and Chinese and for our shared passion in medicine and evolutionary biology. Dr. McNutt deserves special thanks for his sustained support of multiple iterations of manuscript edits in professional English style. I would like to thank Dr. Raj P. Kapur (Seattle Children s Hospital and University of Washington School of Medicine, Seattle, WA) for his critical review of my manuscript and intellectual interactions with me along the process as I was formulating the scientific concept of this manuscript. I would like to thank Dr. Joe Rutledge (Seattle Children s Hospital and University of Washington School of Medicine, Seattle, WA) for his encouragement and support of my scientific pursuits. I would also like to take this opportunity to thank Dr. Harry W. Taber (Wadsworth Center, New York State of Public Health, Albany, NY) for his graduate mentorship early in my career with the emphasis on the spirit of a “free thinker”.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Glossary

Syntrophy is a nutritional term. It involves cross-feeding or transfer of compounds between species, such that neither species grows well in the absence of the other, and both species benefit from the presence of the other. This term has been expanded to include interdependence between organisms to facilitate defenses against predators or inhibitory substances, such as antibiotics.

Prototrophy is used to characterize an organism that is able to synthesize all organic compounds for growth from simple sugars or inorganic compounds.

Auxotrophy is used to characterize an organism that is unable to synthesize a particular organic compound(s) required for growth from simple sugars or inorganic compounds.

Sympatric is used to characterize biological populations of species that exist in the same geographic or physical area and regularly encounter each other.

Allopatric is used to characterize biological populations of the same species that are separated by a geographic or physical barrier.