The Pseudomonas aeruginosa Complement of Lactate Dehydrogenases Enables Use of
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            -Lactate and Metabolic Cross-Feeding

Lin, Yu Cheng; Cornell, William Cole; Jo, Jeanyoung; Price-Whelan, Alexa; Dietrich, Lars E. P.

doi:10.1128/mbio.00961-18

Cited by 44 publications

(44 citation statements)

References 49 publications

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“…Strong interactions between P. aeruginosa and various Streptococci also have been reported (28), although the importance of metabolite cross-feeding in mediating these interactions remains incompletely understood (57). Finally, in the model Pseudomonas supplied small amounts of D-lactate for Prevotella and Staphylococcus consumption, a prediction consistent with an in vitro study showing P. aeruginosa anaerobic production of the LldA enzyme catalyzing D-lactate synthesis (58).…”

Section: Resultssupporting

confidence: 82%

Metabolic Modeling of Cystic Fibrosis Airway Communities Predicts Mechanisms of Pathogen Dominance

Henson

Orazi

Phalak

et al. 2019

Preprint

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5Cystic fibrosis (CF) is a fatal genetic disease characterized by chronic lung infections due to aberrant 1 6 mucus production and the inability to clear invading pathogens. The traditional view that CF infections 1 7 are caused by a single pathogen has been replaced by the realization that the CF lung usually is colonized 1 8 by a complex community of bacteria, fungi and viruses. To help unravel the complex interplay between 1 9 the CF lung environment and the infecting microbial community, we developed a community metabolic 2 0 CF lung metabolomics and 16S sequencing could provide important insights into disease progression and 3 2 treatment efficacy. 3 3 Importance 3 4Cystic fibrosis (CF) is a genetic disease in which chronic airway infections and lung inflammation result 3 5 in respiratory failure. CF airway infections are usually caused by bacterial communities that are difficult 3 6 to eradicate with available antibiotics. Using species abundance data for clinically stable adult CF patients 3 7 assimilated from three published studies, we developed a metabolic model of CF airway communities to 3 8 better understand the interactions between bacterial species and between the bacterial community and the 3 9 lung environment. Our model predicted that clinically-observed CF pathogens could establish dominance 4 0 over other community members across a range of lung nutrient conditions. Heterogeneity of species 4 1 abundances across 75 patient samples could be predicted by assuming that sample-to-sample 4 2 heterogeneity was attributable to random variations in the CF nutrient environment. Our model 4 3 predictions provide new insights into the metabolic determinants of pathogen dominance in the CF lung 4 4 and could facilitate the development of improved treatment strategies. 4 5 4 6shaping community composition and behavior, and the impact of community composition on the efficacy 7 1 of antibiotic treatment regimens. 7 2In silico metabolic modeling has emerged as a powerful approach for analyzing complex microbial 7 3 communities by integrating genome-scale reconstructions of single-species metabolism within 7 4 mathematical descriptions of metabolically interacting communities (11, 12). Modeled species 7 5 interactions typically include competition for host-derived nutrients and cross-feeding of secreted 7 6 byproducts such as organic acids, alcohols and amino acids between species (13, 14). Due to challenges 7 7 in developing manually curated reconstructions of poorly studied species, including those present in the 7 8 CF lung, most in silico community models have been restricted to ~5 microbial species (15-17) and fail to 7 9adequately cover the diversity of in vivo communities. This limitation can be overcome in bacterial 8 0 communities by using semi-curated reconstructions developed through computational pipelines such as 8 1 the ModelSeed (18), AGORA (19) and other methods (20). Given the availability of suitable single-strain 8 2 metabolic reconstructions, a number of alternative methods have been develo...

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Section: Resultssupporting

confidence: 82%

Metabolic Modeling of Cystic Fibrosis Airway Communities Predicts Mechanisms of Pathogen Dominance

Henson

Orazi

Phalak

et al. 2019

Preprint

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“…Although the mechanism by which L. lactis induced growth in this co‐culture setting is unclear, 1 possible explanation is related to L. lactis ’s (anaerobic bacteria) capability to convert glucose (sugar in the mucin) into lactate . The lactate produced fermentatively by L. lactis and mucin may serve as an electron donor for aerobic respiration of Pseudomonas and cause proliferation of certain strains …”

Section: Discussionmentioning

confidence: 99%

The impact of Lactococcus lactis (probiotic nasal rinse) co‐culture on growth of patient‐derived strains of Pseudomonas aeruginosa

Cho

Skinner

Lim

et al. 2020

Int Forum Allergy Rhinol

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Background:The Lactococcus strain of bacteria has been introduced as a probiotic nasal rinse for alleged salubrious effects on the sinonasal bacterial microbiome. However, data regarding interactions with pathogenic bacteria within the sinuses are lacking. The purpose of this study is to assess the interaction between L. lactis and patient-derived Pseudomonas aeruginosa, an opportunistic pathogen in recalcitrant chronic rhinosinusitis (CRS). Methods:Commercially available probiotic suspension containing L. lactis W136 was grown in an anaerobic chamber and colonies were isolated. Colonies were co-cultured with patient-derived P. aeruginosa strains in the presence of porcine gastric mucin (mimicking human mucus) for 72 hours. P. aeruginosa cultures without L. lactis served as controls. Colony forming units (CFUs) were compared.Results: Six P. aeruginosa isolates collected from 5 CRS patients (3 isolates from cystic fibrosis [CF], 1 mucoid strain) and laboratory strain PAO1 were co-cultured with L. lactis. There was no statistical difference in CFUs of 5 P. aeruginosa isolates grown with L. lactis compared to CFUs without presence of L. lactis. CFU counts were much higher when the mucoid strain was co-cultured with L. lactis (CFU +L.lactis = 1.9 × 108 ± 1.44 × 107, CFU -L.lactis = 1.3 × 108 ± 8.9 × 106, p = 0.01, n = 7). L. lactis suppressed the growth of 1 P. aeruginosa strain (CFU +L.lactis = 2.15 × 108 ± 2.9 × 107, CFU -L.lactis = 3.95 × 108 ± 4.8 × 106, p = 0.03, n = 7). Conclusion:L. lactis suppressed the growth of 1 patient P. aeruginosa isolate and induced growth of another (a mucoid strain) in in vitro co-culture se ing in the presence of mucin. Further experiments are required to assess the underlying interactions between L. lactis and P. aeruginosa. C 2020 ARS-AAOA, LLC. How to Cite this Article: Cho D-Y, Skinner D, Lim DJ, et al. The impact of Lactococcus lactis (probiotic nasal rinse) co-culture on growth of patient-derived strains of Pseudomonas aeruginosa. Int Forum Allergy Rhinol. 2020;10:444-449.

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“…More interestingly, they showed that in the absence of bicarbonate (with HEPES) the apical P. aeruginosa CFU increased significantly and even more in the presence of high glucose (15 mM), suggesting that CFRD and acidity contribute to worsen infections [63]. On the other hand, in addition to reduce the pH, the increased lactate may contribute to the development of infections by supplying a carbon source to bacteria [64]. Also, particularly in diabetic patients, the glucose metabolism in bacteria may be an additional source of lactate, contributing to a reduced pH environment and to the microfilm formation [64,65].…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, in addition to reduce the pH, the increased lactate may contribute to the development of infections by supplying a carbon source to bacteria [64]. Also, particularly in diabetic patients, the glucose metabolism in bacteria may be an additional source of lactate, contributing to a reduced pH environment and to the microfilm formation [64,65].…”

Section: Discussionmentioning

confidence: 99%

Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretion

Valdivieso

Clauzure

Massip-Copiz

et al. 2019

Cell. Mol. Life Sci.

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Mutations in the gene encoding the CFTR chloride channel produce cystic fibrosis (CF). CF patients are more susceptible to bacterial infections in lungs. The most accepted hypothesis sustains that a reduction in the airway surface liquid (ASL) volume favor infections. Alternatively, it was postulated that a reduced HCO3transport through CFTR leads to a decreased ASL pH, favoring bacterial colonization. The issue is controversial since recent data from cultured primary cells and CF children showed normal pH values in the ASL. We have reported previously a decreased mitochondrial Complex I (mCx-I) activity in cultured cells with impaired CFTR activity. Thus, we hypothesized that the reduced mCx-I activity could lead to increased lactic acid production (Warburg-like effect) and reduced extracellular pH (pHe). In agreement with this idea, we report here that cells with impaired CFTR function (intestinal Caco-2/pRS26, transfected with an shRNA-CFTR, and lung IB3-1 CF cells) have a decreased pHe. These cells showed increased lactate dehydrogenase (LDH) activity, LDH-A expression, and lactate secretion. Similar effects were reproduced in control cells stimulated with recombinant IL-1β. The c-Src and JNK inhibitors PP2 and SP600125 were able to increase the pHe, although the differences between control and CFTR-impaired cells were not fully compensated. Noteworthy, the LDH inhibitor oxamate completely restored the pHe of the intestinal Caco-2/pRS26 cells and have a significant effect in lung IB3-1 cells; therefore, an increased lactic acid secretion seems to be the key factor that determine a reduced pHe in these epithelial cells.

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The Pseudomonas aeruginosa Complement of Lactate Dehydrogenases Enables Use of d - and l -Lactate and Metabolic Cross-Feeding

Cited by 44 publications

References 49 publications

Metabolic Modeling of Cystic Fibrosis Airway Communities Predicts Mechanisms of Pathogen Dominance

Metabolic Modeling of Cystic Fibrosis Airway Communities Predicts Mechanisms of Pathogen Dominance

The impact of Lactococcus lactis (probiotic nasal rinse) co‐culture on growth of patient‐derived strains of Pseudomonas aeruginosa

Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretion

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