Cystic Fibrosis Lung Infections: Polymicrobial, Complex, and Hard to Treat

Filkins, Laura; O’Toole, George A.

doi:10.1371/journal.ppat.1005258

Cited by 179 publications

(168 citation statements)

References 30 publications

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“…While the importance of these communities in infectious disease has long been understood, the advent of cutting-edge technologies is yielding new insights into the complexities and impacts of multi-species infections on human health (Marsland and Gollwitzer 2014; Surette 2013; Lynch and Bruce 2013; Price et al 2013; Lipuma 2010; Rogers et al 2010; Lyczak, Cannon, and Pier 2002; Filkins and O'Toole 2015). Despite these advances, the impact of polymicrobial interactions on infectious disease remains difficult to dissect in a laboratory environment.…”

Section: Introductionmentioning

confidence: 99%

Interactions between Pseudomonas aeruginosa and Staphylococcus aureus during co-cultivations and polymicrobial infections

Nguyen

Oglesby-Sherrouse

2016

Appl Microbiol Biotechnol

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Pseudomonas aeruginosa and Staphylococcus aureus are versatile bacterial pathogens and common etiological agents in polymicrobial infections. Microbial communities containing both of these pathogens are shaped by interactions ranging from parasitic to mutualistic, with the net impact of these interactions in many cases resulting in enhanced virulence. Polymicrobial communities of these organisms are further defined by multiple aspects of the host environment, with important implications for disease progression and therapeutic outcomes. This mini-review highlights the impact of these interactions on the host and individual pathogens, the molecular mechanisms that underly these interactions, and host-specific factors that drive interactions between these two important pathogens.

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Section: Introductionmentioning

confidence: 99%

Interactions between Pseudomonas aeruginosa and Staphylococcus aureus during co-cultivations and polymicrobial infections

Nguyen

Oglesby-Sherrouse

2016

Appl Microbiol Biotechnol

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“…The thick mucus covering the CF airway is an ideal environment for a polymicrobial community, including pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus, and the Burkholderia cepacia species complex (Bcc) (Filkins and O'Toole 2015;Parkins and Floto 2015;Huang and LiPuma 2016). The ecological diversity and the dynamics of this community complicate diagnosis and treatment (Rau et al 2012).…”

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confidence: 99%

Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs

et al. 2017

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Chronic bacterial infections of the lung are the leading cause of morbidity and mortality in cystic fibrosis patients. Tracking bacterial evolution during chronic infections can provide insights into how host selection pressures-including immune responses and therapeutic interventions-shape bacterial genomes. We carried out genomic and phenotypic analyses of 215 serially collected Burkholderia cenocepacia isolates from 16 cystic fibrosis patients, spanning a period of 2-20 yr and a broad range of epidemic lineages. Systematic phenotypic tests identified longitudinal bacterial series that manifested progressive changes in liquid media growth, motility, biofilm formation, and acute insect virulence, but not in mucoidy. The results suggest that distinct lineages follow distinct evolutionary trajectories during lung infection. Pan-genome analysis identified 10,110 homologous gene clusters present only in a subset of strains, including genes restricted to different molecular types. Our phylogenetic analysis based on 2148 orthologous gene clusters from all isolates is consistent with patient-specific clades. This suggests that initial colonization of patients was likely by individual strains, followed by subsequent diversification. Evidence of clonal lineages shared by some patients was observed, suggesting inter-patient transmission. We observed recurrent gene losses in multiple independent longitudinal series, including complete loss of Chromosome III and deletions on other chromosomes. Recurrently observed loss-of-function mutations were associated with decreases in motility and biofilm formation. Together, our study provides the first comprehensive genome-phenome analyses of B. cenocepacia infection in cystic fibrosis lungs and serves as a valuable resource for understanding the genomic and phenotypic underpinnings of bacterial evolution.

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“…Studies have further shown that in vitro biofilms observed under nutrient-limited conditions are increasingly recalcitrant to antibiotic therapy due to enhanced tolerance (22). The design and delivery of antimicrobial therapy targeted against the polymicrobial respiratory biofilm is, therefore, challenging (23).…”

mentioning

confidence: 99%

A Low-Molecular-Weight Alginate Oligosaccharide Disrupts Pseudomonal Microcolony Formation and Enhances Antibiotic Effectiveness

Pritchard

Powell

Jack

et al. 2017

Antimicrob Agents Chemother

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In chronic respiratory disease, the formation of dense, 3-dimensional "microcolonies" by Pseudomonas aeruginosa within the airway plays an important role in contributing to resistance to treatment. An in vitro biofilm model of pseudomonal microcolony formation using artificial-sputum (AS) medium was established to study the effects of low-molecular-weight alginate oligomers (OligoG CF-5/20) on pseudomonal growth, microcolony formation, and the efficacy of colistin. The studies employed clinical cystic fibrosis (CF) isolates (n ϭ 3) and reference nonmucoid and mucoid multidrug-resistant (MDR) CF isolates (n ϭ 7). Bacterial growth and biofilm development and disruption were studied using cell viability assays and image analysis with scanning electron and confocal laser scanning microscopy. Pseudomonal growth in AS medium was associated with increased ATP production (P Ͻ 0.05) and the formation (at 48 h) of discrete (Ͼ10-m) microcolonies. In conventional growth medium, colistin retained an ability to inhibit growth of planktonic bacteria, although the MIC was increased (0.1 to 0.4 g/ml) in AS medium compared to Mueller-Hinton (MH) medium. In contrast, in an established-biofilm model in AS medium, the efficacy of colistin was decreased. OligoG CF-5/20 (Ն2%) treatment, however, induced dose-dependent biofilm disruption (P Ͻ 0.05) and led to colistin retaining its antimicrobial activity (P Ͻ 0.05). While circular dichroism indicated that OligoG CF-5/20 did not change the orientation of the alginate carboxyl groups, mass spectrometry demonstrated that the oligomers induced dose-dependent (Ͼ0.2%; P Ͻ 0.05) reductions in pseudomonal quorum-sensing signaling. These findings reinforce the potential clinical significance of microcolony formation in the CF lung and highlight a novel approach to treat MDR pseudomonal infections.

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Cystic Fibrosis Lung Infections: Polymicrobial, Complex, and Hard to Treat

Cited by 179 publications

References 30 publications

Interactions between Pseudomonas aeruginosa and Staphylococcus aureus during co-cultivations and polymicrobial infections

Interactions between Pseudomonas aeruginosa and Staphylococcus aureus during co-cultivations and polymicrobial infections

Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs

A Low-Molecular-Weight Alginate Oligosaccharide Disrupts Pseudomonal Microcolony Formation and Enhances Antibiotic Effectiveness

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