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

Abstract

To cite this article: Xuan Qin (2016) Chronic pulmonary pseudomonal infection in patients with cystic fibrosis: A model for early phase symbiotic evolution, Critical Reviews in Microbiology, 42:1, 144-157, DOI: 10.3109/1040841X.2014 AbstractGain 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.

DivergentIn vitroMIC Characteristics and underlying isogenic mutations in host-specializedPseudomonas aeruginosa

“…Our study also showed the isogenic isolates were often auxotrophic for either arginine and/or methionine. We have also demonstrated that nutritional cross-feeding supported co-growth between prototroph and auxotroph complements with intra-clonal preferences; thus we postulate that multicellular resistant syntrophy is the mechanism of pseudomonal persistence without clearance and serendipitously, the absence of repeat attacks thereafter by clonally unrelated wild-type Pa strain(s) in CF airways (3, 27). High level resistance to aztreonam and carbapenems in CF Pa has long been be linked to inactivation or alteration of a drug transporter porin D and many adaptive mutations in regulatory determinants, such as mexR, nalC and nalD , contributing to mexAB-oprM hyper-expression (28–30).…”

“…With the genomic evidence of on average of 18% CDSs mutations in the 19 CF Pa genomes, we believe that the divergent MICs along with other structural and functional diversities are the net results of combined impact of these mutations in CF Pa. The distinct biological changes associated with CF Pa once again represent an evolutionary novelty due to their prolonged confinement to a specific host airway environment with selective pressure (3).…”

“…In the airway environment of patients with cystic fibrosis (CF), isolates of Pseudomonas aeruginosa (Pa) and other common bacterial cohabitants undergo host airway niche adaption and virulence attenuation (1, 2). As soon as the organism enters the CF airway, it is under enormous host selective pressure that is reflected by pseudomonal transition into a hypermutable state with loss of function mutations in mutS and mutL (3–6). The diverse MIC patterns generated among co-isolates are in part a result of pseudomonal isogenic divergence in response to host and antimicrobial pressure (3, 7).…”

“…As soon as the organism enters the CF airway, it is under enormous host selective pressure that is reflected by pseudomonal transition into a hypermutable state with loss of function mutations in mutS and mutL (3–6). The diverse MIC patterns generated among co-isolates are in part a result of pseudomonal isogenic divergence in response to host and antimicrobial pressure (3, 7). Similarly, bacterial small colony variants (SCV) have been described to coexist as isogenic variants in vitro (8).…”

“…The so-called “persister” organisms frequently show “heteroresistance” that describes a phenomenon where subpopulations of isogenic bacteria exhibit a range of susceptibilities to a particular antibiotic agent (19). Clinical laboratories are currently not equipped or adequately guided for appropriate testing or interpretation of non-homogeneous bacterial isolates or co-isolates of clonal associates that produce highly variable and isogenic heteroresistance patterns (3, 19, 20).…”