Biofilm Inhibitor Taurolithocholic Acid Alters Colony Morphology, Specialized Metabolism, and Virulence of <i>Pseudomonas aeruginosa</i>

Condren, Alanna R.; Kahl, Lisa Juliane; Boelter, Gabriela; Kritikos, George; Banzhaf, Manuel; Dietrich, Lars E. P.; Sanchez, Laura M.

doi:10.1021/acsinfecdis.9b00424

Cited by 13 publications

(29 citation statements)

References 63 publications

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“…As metabolism often underlies phenotypic changes, we hypothesized that different ASM formulations induced different chemotypes of PAO1. P. aeruginosa has a well characterized specialized metabolome chemical signals produced by microorganisms to interact with their environment (46,47)), including six molecular families: homoserine lactones (HSLs), rhamnolipids (RHLs), alkyl quinolones (AQs), phenazines (PHZs), and the siderophores pyochelin (PCH) and pyoverdine (PVD) (48)(49)(50). These compounds are chemically and functionally diverse and include quorum sensors, small molecule virulence factors, and natural products.…”

Section: P Aeruginosa Produces Similar Specialized Metabolites In Almentioning

confidence: 99%

“…These compounds are chemically and functionally diverse and include quorum sensors, small molecule virulence factors, and natural products. P. aeruginosa specialized metabolites have been detected in CF sputum (32)(33)(34) and associated with pathogenicity and virulence (24,50,51).…”

Section: P Aeruginosa Produces Similar Specialized Metabolites In Almentioning

confidence: 99%

“…43,44 P. aeruginosa has a well-characterized specialized metabolome, including phenazines, quinolones, rhamnolipids, and the siderophores pyoverdine and pyochelin. 37,45,46 P. aeruginosa specialized metabolites have been detected in CF samples 30,34,35,[47][48][49][50][51][52][53] and are associated with pathogenicity and virulence. 29,37,38 As nutrient concentration varies between ASM formulations, alteration in production levels of these metabolites by P. aeruginosa may influence interpretation of virulence-related phenotypes.…”

Section: Asm Formulation Variation Stimulates Differential Production Of Small Moleculementioning

confidence: 99%

“…30,[34][35][36] As P. aeruginosa specialized metabolites are associated with virulence phenotypes, their measurement can be used to understand how different nutrient availability in ASM formulations affect P. aeruginosa virulence. 37,38 We show that different ASM formulations induce differential production of P. aeruginosa PAO1 small molecule virulence factors, including members of the phenazine, quinolone, rhamnolipid, pyochelin, and pyoverdine molecular families, which is partially driven by the inclusion of commercial porcine gastric mucin (PGM) in the media.…”

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confidence: 99%

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Commercial porcine gastric mucin contributes to variation in production of small molecule virulence factors byPseudomonas aeruginosawhen cultured in different formulations of artificial sputum medium

Phelan

2021

Preprint

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Artificial sputum medium (ASM) is a class of in vitro bacterial culture medium intended to mimic the nutritional environment of cystic fibrosis (CF) pulmonary mucus. One of the most commonly studied microbes in ASM is Pseudomonas aeruginosa, a prevalent and dangerous pathogen of the CF pulmonary microbiome. Many ASM formulations have been reported in literature, with differing nutrient concentrations and availability. Here, we show that common formulations of ASM yield different phenotypes and chemotypes of P. aeruginosa. Further, we demonstrate that iron in commercial porcine gastric mucin (PGM) is sufficient to alter production of P. aeruginosa siderophores in the chemically defined ASM, synthetic CF medium 1 (SCFM1). These results highlight that the choice of ASM formulation for in vitro investigations of microbial pathogenicity, physiology, and interactions should be carefully considered.IMPORTANCEIn vitro culture media are being developed to resemble the in vivo nutritional environment more closely. These culture media are used to investigate microbial pathogenicity and ecology in environments that are more reflective of disease states. In cystic fibrosis (CF), a number of different artificial sputum media (ASM) formulations have been created to recapitulate the CF lung environment. However, these ASM have different sources and concentrations of nutrients. Here, we cultured Pseudomonas aeruginosa in nine different formulations of ASM. P. aeruginosa is the primary pathogen causing lung infection in CF.We show that different ASM formulations lead to different phenotypes and chemotypes by P. aeruginosa and one component of ASM, mucin, contains high levels of iron, which may affect P. aeruginosa physiology.

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Section: P Aeruginosa Produces Similar Specialized Metabolites In Almentioning

confidence: 99%

Section: P Aeruginosa Produces Similar Specialized Metabolites In Almentioning

confidence: 99%

Section: Asm Formulation Variation Stimulates Differential Production Of Small Moleculementioning

confidence: 99%

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confidence: 99%

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Commercial porcine gastric mucin contributes to variation in production of small molecule virulence factors byPseudomonas aeruginosawhen cultured in different formulations of artificial sputum medium

Phelan

2021

Preprint

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“…This approach has been applied to decipher microbe-microbe chemical communication and changes in metabolite production between microbial colonies grown in different environmental conditions. (6,26,27) IMS is especially valuable for the comparison of metabolites of defined strains because changes in production, as measured by ion intensity, can be specifically and rapidly detected and evaluated in the context of genetic differences. (28) IMS analysis of WT V. fischeri compared to Biofilm-Up and Biofilm-Down strains revealed that several metabolites were significantly upregulated in Biofilm-Up compared to the other strains.…”

Section: Introductionmentioning

confidence: 99%

Discovery of a microbially produced small molecule in a host-specific organ

Zink

Tarnowski

Lazzara

et al. 2020

Preprint

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The lifelong relationship between the Hawaiian bobtail squid, Euprymna scolopes, and its microbial symbiont, Vibrio fischeri, represents a simplified model system for studying microbiome establishment and maintenance. The bacteria colonize a dedicated symbiotic light organ in the squid, from which bacterial luminescence camouflages the hosts in a process termed counterillumination. The squid hosts hatch without their symbionts, which must be acquired from the ocean amid a diversity of non-beneficial bacteria, so precise molecular communication is required for initiation of the specific relationship. It is therefore likely that there may be specialized metabolites used in the light organ microenvironment to modulate these processes. To identify small molecules that may influence the establishment of this symbiosis, we used imaging mass spectrometry to analyze metabolite production in V. fischeri with altered biofilm production, which correlates directly to colonization capability in its host. 'Biofilm-Up' and 'Biofilm-Down' mutants were compared to a wild-type strain, and masses that were more abundantly produced by the biofilm-up mutant were detected. Using a combination of structure elucidation and synthetic chemistry, one such signal was determined to be a diketopiperazine, cyclo(D-histidyl-L-proline). This diketopiperazine modulated luminescence in V. fischeri and, using label-free imaging mass spectrometry, was directly detected in the light organ of the colonized host. This work highlights the continued need for untargeted discovery efforts in host-microbe interactions and showcases the benefits of the squid-Vibrio system for identification and characterization of small molecules that modulate microbiome behaviors.

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Utilizing imaging mass spectrometry to analyze microbial biofilm chemical responses to exogenous compounds

McCaughey

Trebino

Yildiz

et al. 2022

Methods in Enzymology

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Biofilm Inhibitor Taurolithocholic Acid Alters Colony Morphology, Specialized Metabolism, and Virulence of Pseudomonas aeruginosa

Cited by 13 publications

References 63 publications

Commercial porcine gastric mucin contributes to variation in production of small molecule virulence factors byPseudomonas aeruginosawhen cultured in different formulations of artificial sputum medium

Commercial porcine gastric mucin contributes to variation in production of small molecule virulence factors byPseudomonas aeruginosawhen cultured in different formulations of artificial sputum medium

Discovery of a microbially produced small molecule in a host-specific organ

Utilizing imaging mass spectrometry to analyze microbial biofilm chemical responses to exogenous compounds

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