<i>Pseudomonas aeruginosa</i> Population Diversity and Turnover in Cystic Fibrosis Chronic Infections

Mowat, Eilidh; Paterson, Steve; Fothergill, Joanne L.; Wright, Elli A.; Ledson, M.J.; Walshaw, Martin; Brockhurst, Michael A.; Winstanley, Craig

doi:10.1164/rccm.201009-1430oc

Cited by 233 publications

(286 citation statements)

References 44 publications

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“…These episodes are treatable with antibiotic therapy, but little is known about the pathophysiology of CF exacerbations (52). Some evidence indicates that P. aeruginosa strains express higher levels of virulence factors during exacerbation, including pyocyanin, elastase and exotoxin A (53)(54)(55). Few studies have looked at inflammasome activators, though a study in children with early intermittent infection did not see any correlation between T3SS exotoxins and exacerbation (56).…”

Section: Discussionmentioning

confidence: 99%

Clinical Isolates of Pseudomonas aeruginosa from Chronically Infected Cystic Fibrosis Patients Fail To Activate the Inflammasome during Both Stable Infection and Pulmonary Exacerbation

Huus

Joseph

Zhang

et al. 2016

The Journal of Immunology

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Immune recognition of pathogen-associated ligands leads to assembly and activation of inflammasomes, resulting in the secretion of inflammatory cytokines IL-1β and IL-18 and an inflammatory cell death called pyroptosis. Inflammasomes are important for protection against many pathogens, but their role during chronic infectious disease is poorly understood. Pseudomonas aeruginosa is an opportunistic pathogen that persists in the lungs of cystic fibrosis (CF) patients and may be responsible for the repeated episodes of pulmonary exacerbation characteristic of CF. P. aeruginosa is capable of inducing potent inflammasome activation during acute infection. We hypothesized that to persist within the host during chronic infection, P. aeruginosa must evade inflammasome activation, and pulmonary exacerbations may be the result of restoration of inflammasome activation. We therefore isolated P. aeruginosa from chronically infected CF patients during stable infection and exacerbation and evaluated the impact of these isolates on inflammasome activation in macrophages and neutrophils. P. aeruginosa isolates from CF patients failed to induce inflammasome activation, as measured by the secretion of IL-1β and IL-18 and by pyroptotic cell death, during both stable infection and exacerbation. Inflammasome evasion likely was due to reduced expression of inflammasome ligands and reduced motility and was not observed in environmental isolates or isolates from acute, non-CF infection. These results reveal a novel mechanism of pathogen adaptation by P. aeruginosa to avoid detection by inflammasomes in CF patients and indicate that P. aeruginosa–activated inflammasomes are not involved in CF pulmonary exacerbations.

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Section: Discussionmentioning

confidence: 99%

Clinical Isolates of Pseudomonas aeruginosa from Chronically Infected Cystic Fibrosis Patients Fail To Activate the Inflammasome during Both Stable Infection and Pulmonary Exacerbation

Huus

Joseph

Zhang

et al. 2016

The Journal of Immunology

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“…The observed increased incidence of aminoglycoside and fluoroquinolone nonsusceptibility in PES during our study may indicate an increased treatment requirement and treatment burden in those infected with PES. PES has been demonstrated to be capable of tremendous within-patient phenotypic diversity, as measured by colony morphology, motility, protease production, auxotrophy, siderophore production, antibiotic resistance, quorum sensing, and growth patterns, similar to the within-patient heterogeneity of LES (51,52).…”

Section: Figmentioning

confidence: 99%

Twenty-Five-Year Outbreak of Pseudomonas aeruginosa Infecting Individuals with Cystic Fibrosis: Identification of the Prairie Epidemic Strain

et al. 2014

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Transmissible strains of Pseudomonas aeruginosa have been described for cystic fibrosis (CF) and may be associated with a worse prognosis. Using a comprehensive strain biobank spanning 3 decades, we sought to determine the prevalence and stability of chronic P. aeruginosa infection in an adult population. P. aeruginosa isolates from sputum samples collected at initial enrollment in our adult clinic and at the most recent clinic visit were examined by a combination of pulsed-field gel electrophoresis and multilocus sequence typing and compared against a collection of established transmissible and local non-CF bronchiectasis (nCFB) isolates. A total of 372 isolates from 107 patients, spanning 674 patient-years, including 66 patients with matched isolates from initial and final encounters, were screened. A novel clone with increased antibacterial resistance, termed the prairie epidemic strain (PES), was found in 29% (31/107 patients) of chronically infected patients referred from multiple prairie-based CF centers. This isolate was not found in those diagnosed with CF as adults or in a control population with nCFB. While 90% (60/66 patients) of patients had stable infection over a mean of 10.8 years, five patients experienced strain displacement of unique isolates, with PES occurring within 2 years of transitioning to adult care. PES has been present in our cohort since at least 1987, is unique to CF, generally establishes chronic infection during childhood, and has been found in patients at the time of transition of patients from multiple prairie-based CF clinics, suggesting broad endemicity. Studies are under way to evaluate the clinical implications of PES infection.

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“…Chronic infections due to bacterial persistence in the form of biofilm have gained recognition over the last two decades (Hoiby et al, 2001(Hoiby et al, , 2010May et al, 1991). The theory of pseudomonal biofilm assembly on the mucosal surface of CF airway has begun to address bacterial lifestyle changes that include differential gene expression, isogenic divergence, and organized cell-to-cell communication (Boucher, 2004;Mowat et al, 2011;Oliver, 2010;Oliver & Mena, 2010;Whiteley et al, 2001;Wu et al, 2001). However, few studies have directly addressed the question of intraclonal diversity, and even fewer have grappled with the confounding fact that heightened bacterial virulence is associated with bacteria in planktonic growth state (Fux et al, 2005;Head & Yu, 2004;Huse et al, 2010;Manos et al, 2008;Palmer, 2005).…”

Section: Accumulation Of Quorum Sensing Deficient Pa Reflects Developmentioning

confidence: 99%

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

Qin

2014

Critical Reviews in Microbiology

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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.

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Pseudomonas aeruginosa Population Diversity and Turnover in Cystic Fibrosis Chronic Infections

Abstract: These results significantly advance our understanding of the within-host population biology of P. aeruginosa during infection of patients with cystic fibrosis, and provide in vivo evidence for a link between pyocyanin production and patient morbidity.

Cited by 233 publications

References 44 publications

Clinical Isolates of Pseudomonas aeruginosa from Chronically Infected Cystic Fibrosis Patients Fail To Activate the Inflammasome during Both Stable Infection and Pulmonary Exacerbation

Clinical Isolates of Pseudomonas aeruginosa from Chronically Infected Cystic Fibrosis Patients Fail To Activate the Inflammasome during Both Stable Infection and Pulmonary Exacerbation

Twenty-Five-Year Outbreak of Pseudomonas aeruginosa Infecting Individuals with Cystic Fibrosis: Identification of the Prairie Epidemic Strain

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

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