Nutritional Cues Control
            <i>Pseudomonas aeruginosa</i>
            Multicellular Behavior in Cystic Fibrosis Sputum

Palmer, Kelli L.; Aye, Lindsay M.; Whiteley, Marvin

doi:10.1128/jb.00185-09

Cited by 110 publications

(210 citation statements)

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“…For example, synergistic and antagonistic behavior between different CF pathogens has been described (Duan et al, 2003;Harrison, 2007;Sibley et al, 2008;Mitchell et al, 2010;Yang et al, 2011;Venkataraman et al, 2014), and the microbial community has been proposed to contain stable and disturbed states, much like those in classical ecology (Conrad et al, 2012). Known chemical characteristics of the CF lung include lowered pH (Tate et al, 2002;Pezzulo et al, 2012), low oxygen tensions (Worlitzsch et al, 2002) and high levels of amino acids, nitrate, iron and phenazines (Grasemann et al, 1998;Jones et al, 2000;Palmer et al, 2007;Ghio et al, 2012;Hunter et al, 2012). In the environment, microbial communities are known to stratify based on oxygen and other chemical gradients (Fenchel and Finlay, 2008;Morris and Schmidt, 2013).…”

Section: Introductionmentioning

confidence: 99%

A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation

et al. 2014

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There is a poor understanding of how the physiology of polymicrobial communities in cystic fibrosis (CF) lungs contributes to pulmonary exacerbations and lung function decline. In this study, a microbial culture system based on the principles of the Winogradsky column (WinCF system) was developed to study the physiology of CF microbes. The system used glass capillary tubes filled with artificial sputum medium to mimic a clogged airway bronchiole. Chemical indicators were added to observe microbial physiology within the tubes. Characterization of sputum samples from seven patients showed variation in pH, respiration, biofilm formation and gas production, indicating that the physiology of CF microbial communities varied among patients. Incubation of homogenized tissues from an explant CF lung mirrored responses of a Pseudomonas aeruginosa pure culture, supporting evidence that end-stage lungs are dominated by this pathogen. Longitudinal sputum samples taken through two exacerbation events in a single patient showed that a two-unit drop in pH and a 30% increase in gas production occurred in the tubes prior to exacerbation, which was reversed with antibiotic treatment. Microbial community profiles obtained through amplification and sequencing of the 16S rRNA gene showed that fermentative anaerobes became more abundant during exacerbation and were then reduced during treatment where P. aeruginosa became the dominant bacterium. Results from the WinCF experiments support the model where two functionally different CF microbial communities exist, the persistent Climax Community and the acute Attack Community. Fermentative anaerobes are hypothesized to be the core members of the Attack Community and production of acidic and gaseous products from fermentation may drive developing exacerbations. Treatment targeting the Attack Community may better resolve exacerbations and resulting lung damage.

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Section: Introductionmentioning

confidence: 99%

A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation

et al. 2014

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“…Whilst a dry-powder preparation of mannitol is an approved osmolyte therapy for use in CF patients, it is important to exercise caution when considering the clinical significance of the present study, as clearly the nutritional cues present in the CF airways are not equivalent to those present in MYEM. We have observed that supplementation of synthetic CF sputum medium (SCFM; Palmer et al, 2007) with mannitol supports EPS biosynthesis (C. Denman & A. Brown, unpublished observations).…”

Section: Discussionmentioning

confidence: 99%

Growth on mannitol-rich media elicits a genome-wide transcriptional response in Burkholderia multivorans that impacts on multiple virulence traits in an exopolysaccharide-independent manner

et al. 2014

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In common with other members of the Burkholderia cepacia complex (BCC), Burkholderia multivorans is capable of producing exopolysaccharide (EPS) when grown on certain mannitolrich media. The significance of the resulting mucoid phenotype and the genome-wide response to mannitol has never been characterized despite its clinical relevance following the approval of a dried-powder preparation of mannitol as an inhaled osmolyte therapy for cystic fibrosis (CF) patients. In the present study we defined the transcriptional response of B. multivorans ATCC 17616, a model genome-sequenced strain of environmental origin, to growth on mannitol-rich yeast extract media (MYEM). EPS-dependent and -independent impact of MYEM on virulenceassociated traits was assessed in both strain ATCC 17616 and the CF isolate B. multivorans C1576. Our studies revealed a significant transcriptional response to MYEM encompassing approximately 23 % of predicted genes within the genome. Strikingly, this transcriptional response identified that EPS induction occurs in ATCC 17616 without the upregulation of the bce-I and bce-II EPS gene clusters, despite their pivotal role in EPS biosynthesis. Of approximately 20 differentially expressed putative virulence factors, 16 exhibited upregulation including flagella, ornibactin, oxidative stress proteins and phospholipases. MYEM-grown B. multivorans also exhibited enhanced motility, biofilm formation and epithelial cell invasion. In contrast to these potential virulence enhancements, MYEM-grown B. multivorans C1576 showed attenuated virulence in the Galleria mellonella infection model. All of the observed phenotypic responses occurred independently of EPS production, highlighting the profound impact that mannitol-based growth has on the physiology and virulence of B. multivorans.

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“…aeruginosa strains that initiate infections in CF can produce a huge arsenal of metabolic and virulence factors [16], can use the nutrients in the lung to promote growth [52] and can synthesize many toxic factors, such as pyocyanin, a type III secretion system, a variety of proteases, lipases and phospholipases, rhamnolipids and other potentially toxic factors [16,21,53]. Another key change in the organism associated with virulence in the CF lung is the loss of synthesis of the LPSO side chain [54] combined with the synthesis of the lipid A component as an isoform more likely to promote inflammation [55].…”

Section: Establishment Of Chronic Infectionmentioning

confidence: 99%

Airway epithelial control of Pseudomonas aeruginosa infection in cystic fibrosis

Campodónico

Gadjeva

Paradis-Bleau

et al. 2008

Trends in Molecular Medicine

100

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Defective expression or function of the cystic fibrosis transmembrane conductance regulator (CFTR) underlies the hypersusceptibility of cystic fibrosis (CF) patients to chronic airway infections, particularly with Pseudomonas aeruginosa. CFTR is involved in the specific recognition of P. aeruginosa, thereby contributing to effective innate immunity and proper hydration of the airway surface layer (ASL). In CF, the airway epithelium fails to initiate an appropriate innate immune response, allowing the microbe to bind to mucus plugs that are then not properly cleared because of the dehydrated ASL. Recent studies have identified numerous CFTR-dependent factors that are recruited to the epithelial plasma membrane in response to infection and that are needed for bacterial clearance, a process that is defective in CF patients hypersusceptible to infection with this organism. Pseudomonas aeruginosa in cystic fibrosisCystic fibrosis (CF) is unique among human genetic disorders in that mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a protein whose primary function described to date has been to regulate conductance of ions in and out of cells and intracellular vacuoles, lead to hypersusceptibility to chronic lung infection. Human diseases wherein individuals homozygous for mutant genes are predisposed to infections serve as a firm foundation for understanding the molecular, cellular, physiologic and immunologic aspects of normal and compromised resistance to infection. CF is not just a prime example of how we can learn about normal and pathologic states; it could, in fact, be the only known human genetically determined disease wherein infection with a single pathogen -Pseudomonas aeruginosa -drives the vast majority of morbidity, clinical deterioration and ultimately life-shortening mortality encountered in this disease. In humans with significant compromises to their immune system, such as advanced AIDS, we would normally expect to see a plethora of pathogens take advantage of this debilitated state, but this is not the case in CF.CF is characterized by the emergence and persistence of (and, ultimately, the inability to clear) chronic infection with a variant of P. aeruginosa (mucoid P. aeruginosa) that overproduces a surface polysaccharide known as alginate. The organism undergoes other significant genetic adaptations and selections within the CF lung, and it is the emergence of mucoid P. aeruginosa that is the primary determinant of the clinical course of this disease [1,2]. In those individuals with either an uncommon but fortuitous protective immune response to specific P. aeruginosa antigens [3,4] Histopathologic basis for defining relevant interactions between P.aeruginosa and the CF airway epitheliumAlthough CF is a multisystem disease characterized by GI and nutritional abnormalities, salt loss syndromes and male urogenital abnormalities, the major clinical problem for CF patients is chronic sinopulmonary disease. Therefore, relying on observations made fr...

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Nutritional Cues Control Pseudomonas aeruginosa Multicellular Behavior in Cystic Fibrosis Sputum

Cited by 110 publications

References 0 publications

A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation

A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation

Growth on mannitol-rich media elicits a genome-wide transcriptional response in Burkholderia multivorans that impacts on multiple virulence traits in an exopolysaccharide-independent manner

Airway epithelial control of Pseudomonas aeruginosa infection in cystic fibrosis

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