Clinical significance of microbial infection and adaptation in cystic fibrosis

Abstract

A select group of microorganisms inhabit the airways of individuals with cystic fibrosis. Once established within the pulmonary environment in these patients, many of these microbes adapt by altering aspects of their structure and physiology. Some of these microbes and adaptations are associated with more rapid deterioration in lung function and overall clinical status, whereas others appear to have little effect. Here we review current evidence supporting or refuting a role for the different microbes and their adaptations in contributing to poor clinical outcomes in cystic fibrosis.

FIG. 1.

Prevalences of several common respiratory pathogens in CF as a function of age. (Adapted from the 2008 Annual Data Report of the Cystic Fibrosis Foundation Patient Registry, Bethesda, MD [http://www.cff.org/UploadedFiles/research/ClinicalResearch/2008-Patient-Registry-Report.pdf], with permission. © 2009 Cystic Fibrosis Foundation.)

FIG. 2.

Cycle by which the presence of P. aeruginosa bacteria in the airways of individuals with CF leads to progressive pulmonary injury. In addition to directly damaging lung tissues, P. aeruginosa expresses factors that are recognized by the host immune system, resulting in release of proinflammatory cytokines. These cytokines cause the recruitment of large numbers of neutrophils that upon activation release elastase, collagenase, and oxygen radicals. The result is pulmonary injury as well as impaired bacterial clearance, which in turn leads to increased numbers of bacteria and exacerbation of the cycle.

FIG. 3.

Chest computed tomography scan of an individual with CF showing bronchiectasis. Arrows indicate representative dilated airways that are characteristic of bronchiectasis. (Courtesy of Michelle Prickett.)

FIG. 4.

The mucoid phenotype of P. aeruginosa. The colonies on the left are a mucoid P. aeruginosa strain cultured from a CF patient. On the right, a nonmucoid variant of the same strain cultured from the same patient is shown.

FIG. 5.

Gram-stained sputum specimen from a CF patient infected with mucoid P. aeruginosa. The orange material surrounding the bacteria is alginate (magnification, ×1,000). (Reprinted from reference with permission of the publisher. © 2007-2010 American Society for Clinical Pathology and © 2007-2010 American Journal of Clinical Pathology.)

FIG. 6.

Modifications of P. aeruginosa LPS during CF respiratory infections. (A) Structures of LPSs from strains recovered from the environment, acute infections, or bronchiectasis. The lipid A, core oligosaccharide, and O-antigen polysaccharide components are indicated. In the lower panel, a more detailed structure of lipid A is shown. The large polygons represent the diglucosamine bisphosphate backbone of lipid A, and the staggered lines represent acyl groups. (The placement of the lipid A acyl chain shown in gray is unclear [177, 179].) (B) During early infection in individuals with CF, the O-antigen polysaccharide is frequently lost. Also, palmitate (shown as a red staggered line) and aminoarabinose (shown as a red hexagon) are added to the lipid A portion of LPS. (C) In patients with advanced CF, a hydroxydecanoate chain (shown as a red staggered line) is retained, likely due to mutations in the pagL gene, which encodes a lipid A deacylase (89, 175).

FIG. 7.

The proportion of P. aeruginosa isolates with functional type III secretion systems decreases with duration of infection in CF. TTS⁺, functional type III secretion system. Error bars indicate standard deviations. (Adapted from reference .)

FIG. 8.

Examples of P. aeruginosa colonies of normal morphology (left) and SCVs (right). (Reprinted from reference with permission of the publisher.)