Association between glucose intolerance and bacterial colonisation in an adult population with cystic fibrosis, emergence of Stenotrophomonas maltophilia

Dubois, Catherine; Boudreau, Valérie; Tremblay, François; Lavoie, Annick; Berthiaume, Yves; Rabasa‐Lhoret, Rémi; Coriati, Adèle

doi:10.1016/j.jcf.2017.01.018

Cited by 13 publications

(7 citation statements)

References 36 publications

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“…maltophilia is an important colonizer in the lungs of people with CF and infects anywhere from 3 to 15% of CF patients, with a reported prevalence increasing over the last decade (3,6,7). The presence of S. maltophilia has been linked to poor clinical outcomes, including decreased time to exacerbation, increased risk of death or transplant, CF-related diabetes, and decreased lung function (3,(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). While S. maltophilia has not been proven causative for these outcomes, it can promote lung inflammation (19,20) and is inherently multidrug resistant (13,21).…”

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confidence: 99%

Stenotrophomonas maltophilia Differential Gene Expression in Synthetic Cystic Fibrosis Sputum Reveals Shared and Cystic Fibrosis Strain-Specific Responses to the Sputum Environment

et al. 2019

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Stenotrophomonas maltophilia is a Gram-negative opportunistic pathogen that can infect the lungs of people with cystic fibrosis (CF). The highly viscous mucus in the CF lung, expectorated as sputum, serves as the primary nutrient source for microbes colonizing this site and induces virulence-associated phenotypes and gene expression in several CF pathogens. Here, we characterized the transcriptional responses of three S. maltophilia strains during exposure to synthetic CF sputum medium (SCFM2) to gain insight into how this organism interacts with the host in the CF lung. These efforts led to the identification of 881 transcripts differentially expressed by all three strains, many of which reflect the metabolic pathways used by S. maltophilia in sputum, as well as altered stress responses. The latter correlated with increased resistance to peroxide exposure after pregrowth in SCFM2 for two of the strains. We also compared the SCFM2 transcriptomes of two S. maltophilia CF isolates to that of the acute infection strain, S. maltophilia K279a, allowing us to identify CF isolate-specific signatures in differential gene expression. The expression of genes from the accessory genomes was also differentially altered in response to SCFM2. Finally, a number of biofilm-associated genes were differentially induced in SCFM2, particularly in K279a, which corresponded to increased aggregation and biofilm formation in this strain relative to both CF strains. Collectively, this work details the response of S. maltophilia to an environment that mimics important aspects of the CF lung, identifying potential survival strategies and metabolic pathways used by S. maltophilia during infections. IMPORTANCE Stenotrophomonas maltophilia is an important infecting bacterium in the airways of people with cystic fibrosis (CF). However, compared to the other CF pathogens, S. maltophilia has been relatively understudied. The significance of our research is to provide insight into the global transcriptomic changes of S. maltophilia in response to a medium that was designed to mimic important aspects of the CF lung. This study elucidates the overall metabolic changes that occur when S. maltophilia encounters the CF lung and generates a road map of candidate genes to test using in vitro and in vivo models of CF.

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confidence: 99%

Stenotrophomonas maltophilia Differential Gene Expression in Synthetic Cystic Fibrosis Sputum Reveals Shared and Cystic Fibrosis Strain-Specific Responses to the Sputum Environment

et al. 2019

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“…Another important question is whether the relationship between respiratory function and insulin secretory defect is mediated by hyperglycemia. Most of the studies published so far were focused on the relationship between high blood glucose and bacterial lung infection or pulmonary function . However, no data are available on the relationship between high blood glucose and ventilation inhomogeneity.…”

Section: Discussionmentioning

confidence: 99%

“…Impaired glucose tolerance has been associated with increased infection rate from P. aeruginosa , S . aureus , and S. maltophilia as compared to NGT patients . In addition, abnormalities of glucose tolerance, as determined by 1‐h and 2‐h plasma glucose after OGTT, has been associated with poor lung function and higher radiographic score .…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, a more rapid progression of structural lung damage was documented in children with CFRD as compared to those with normal glucose tolerance and this was not reflected by changes in lung function . The mechanism underlying this relationship has not been defined, but it has been hypothesized that patients with hyperglycemia have detectable amount of glucose in the airway that may favor bacterial growth …”

Section: Introductionmentioning

confidence: 99%

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Ventilation inhomogeneity is associated with OGTT‐derived insulin secretory defects in cystic fibrosis

Colombo

Alicandro

Gambazza

et al. 2018

Pediatric Pulmonology

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Progressive deterioration of β-cell function is the main mechanism underlying diabetes in cystic fibrosis (CF). Diabetes negatively impacts the clinical status of CF patients years before its onset. We aimed to evaluate if OGTT-derived indices of β-cell function are associated with early markers of lung disease. We carried out a cross-sectional study on 80 CF patients who performed OGTT, spirometry, and nitrogen-multiple breath washout test. β-cell glucose sensitivity and the insulinogenic indices were used as markers of β-cell function and first-phase insulin response to glucose stimulus. We used sex-and age-adjusted multiple linear regression models to estimate the association between OGTT-derived indices and lung function measures. An increment of β-cell glucose sensitivity equal to its interquartile range was associated with an increase in ppFEV 1 of 7.6 points (95%CI: 0.8; 14.4) as well as with a decrease in LCI of −1.96 units (95%CI: −3.40; −0.51) and in S cond of −0.016 L −1 (95%CI: −0.026; −0.007).The corresponding figures for insulinogenic index were: 8.6 (95%CI: 3.4; 13.9) for ppFEV 1 , −2.03 (95%CI: −3.13; −0.94) for LCI, and −0.014 L −1 (95%CI: −0.021; −0.071) for S cond . When adjusting also for 2-h plasma glucose, both β-cell glucose sensitivity and insulinogenic index remained inversely associated with S cond . Deterioration of βcell function is related to early lung disease in young patients with mild to normal pulmonary function. This relationship is independent from hyperglycemia and mainly involves conductive airways.

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“…CFRD is associated with increased bacterial colonization as well as increased pulmonary exacerbation rate and optimization of chest clearance is therefore vital 63,64. Physiotherapists and exercise physiologists also play a role in collaborating with patients to provide individualized exercise programmes.…”

Section: Managementmentioning

confidence: 99%

<p>Cystic fibrosis-related diabetes: optimizing care with a multidisciplinary approach</p>

Frost

Dyce

Ochota

et al. 2019

DMSO

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Cystic fibrosis-related diabetes (CFRD) is a common complication of cystic fibrosis and can be present in over 50% of adults with the disease. CFRD is associated with poorer clinical outcomes, including accelerated pulmonary function decline and excess morbidity. The management of CFRD is complex and differs from that of type 1 and type 2 diabetes mellitus such that clinicians responsible for the care of people with CFRD must work closely with colleagues across a number of different specialities and disciplines. This review aims to discuss why a multi-disciplinary approach is important and how it can be harnessed to optimize the care of people with CFRD.

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Association between glucose intolerance and bacterial colonisation in an adult population with cystic fibrosis, emergence of Stenotrophomonas maltophilia

Abstract: Prevalence of S. maltophilia was higher in dysglycemic patients, supporting the idea that S. maltophilia is a marker of disease severity in CF.

Cited by 13 publications

References 36 publications

Stenotrophomonas maltophilia Differential Gene Expression in Synthetic Cystic Fibrosis Sputum Reveals Shared and Cystic Fibrosis Strain-Specific Responses to the Sputum Environment

Stenotrophomonas maltophilia Differential Gene Expression in Synthetic Cystic Fibrosis Sputum Reveals Shared and Cystic Fibrosis Strain-Specific Responses to the Sputum Environment

Ventilation inhomogeneity is associated with OGTT‐derived insulin secretory defects in cystic fibrosis

<p>Cystic fibrosis-related diabetes: optimizing care with a multidisciplinary approach</p>

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