Isolation of Indole-3-Aldehyde As a Growth Inhibitor of Legionella pneumophila from Diaion HP-20 Resins Used to Culture the Bacteria

Inoue, Hiroaki; Yajima, Yousuke; Kawano, Genji; Nagasawa, Hiromichi; Sakuda, Shohei

doi:10.4265/bio.9.39

Cited by 6 publications

(4 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A reduction by ≥1 log was observed at 100 μM IAA and 200 μM IPA. As observed previously (44)(45)(46), concentrations of IAA and IPA >3 mM were cytotoxic. We evaluated trpRBA derepression by quantifying trpB expression relative to 16S rRNA at 24 h postinfection (h.p.i.)…”

Section: Resultssupporting

confidence: 87%

“…Confirming the mechanism ascribed to IPA and IAA, ILA does not de-repress the C. trachomatis trpRBA operon. Our findings with IPA and IAA may explain the previously observed effects of these molecules on Legionella pneumophila (44)(45)(46). IPA and IAA reduce L. pneumophila growth under axenic conditions as well as intracellularly within monocytes.…”

Section: Discussionsupporting

confidence: 80%

“…Recent studies have demonstrated that some of these indole derivatives are naturally produced by the human gut microbiome and reach concentrations ranging from 1 to 7 μM in blood (40)(41)(42)(43). Curiously, these same derivatives act, via an unknown mechanism, as antibacterials against Legionella pneumophila (44)(45)(46) and Mycobacterium tuberculosis (47,48), and possess antiinflammatory properties (40,(49)(50)(51). High levels of these indole derivatives in peripheral circulation correlate with protection against inflammatory bowel disease, Crohn's disease, and type 2 diabetes (49,(52)(53)(54)(55); one of them was in clinical trials as an antiinflammatory that reduces Alzheimer's disease progression (56,57).…”

Section: Significancementioning

confidence: 99%

See 2 more Smart Citations

Ammonia generation by tryptophan synthase drives a key genetic difference between genital and ocular Chlamydia trachomatis isolates

Sherchand

Aiyar

2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

A striking difference between genital and ocular clinical isolates of Chlamydia trachomatis is that only the former express a functional tryptophan synthase and therefore can synthesize tryptophan by indole salvage. Ocular isolates uniformly cannot use indole due to inactivating mutations within tryptophan synthase, indicating a selection against maintaining this enzyme in the ocular environment. Here, we demonstrate that this selection occurs in two steps. First, specific indole derivatives, produced by the human gut microbiome and present in serum, rapidly induce expression of C. trachomatis tryptophan synthase, even under conditions of tryptophan sufficiency. We demonstrate that these indole derivatives function by acting as de-repressors of C. trachomatis TrpR. Second, trp operon derepression is profoundly deleterious when infected cells are in an indoledeficient environment, because in the absence of indole, tryptophan synthase deaminates serine to pyruvate and ammonia. We have used biochemical and genetic approaches to demonstrate that expression of wild-type tryptophan synthase is required for the bactericidal production of ammonia. Pertinently, although these indole derivatives de-repress the trpRBA operon of C. trachomatis strains with trpA or trpB mutations, no ammonia is produced, and no deleterious effects are observed. Our studies demonstrate that tryptophan synthase can catalyze the ammonia-generating β-elimination reaction within any live bacterium. Our results also likely explain previous observations demonstrating that the same indole derivatives inhibit the growth of other pathogenic bacterial species, and why high serum levels of these indole derivatives are favorable for the prognosis of diseased conditions associated with bacterial dysbiosis.Chlamydia trachomatis | genital and ocular serovars | tryptophan synthase β-elimination | serine deamination | trp operon de-repression

show abstract

Section: Resultssupporting

confidence: 87%

Section: Discussionsupporting

confidence: 80%

Section: Significancementioning

confidence: 99%

See 1 more Smart Citation

Ammonia generation by tryptophan synthase drives a key genetic difference between genital and ocular Chlamydia trachomatis isolates

Sherchand

Aiyar

2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…oppositifolia . These compounds were identified as ethyl ( R )-pyroglutamate ( 1 ) [ 28 ], indole-3-aldehyde ( 2 ) [ 29 ], (+)-( S )-abscisic acid ( 3 ) [ 30 ], 2 Z -(2,4-dihydroxy-2,6,6-trimethylcyclohexylidene)acetic acid ( 4 ) [ 31 ], azelaic acid ( 5 ) [ 32 ], vanillic acid ( 6 ) [ 33 ], ethyl protocatechuate ( 7 ) [ 34 ], scopoletin ( 8 ) [ 35 ], (-)-evofolin B ( 9 ) [ 36 ], moupinamide ( 10 ) [ 37 ], verrucosin ( 11 ) [ 38 ], and nectandrin B ( 12 ) [ 39 ], based on interpretations of optical rotation values, NMR, and ESI-HRMS spectra (S1–S70 Figs in S1 File ) associated with comparison of data previously reported in literature. This is the first occurrence of compounds 1 – 7 , 9, and 10 in the genus Nectandra .…”

Section: Resultsmentioning

confidence: 99%

Metabolite profile of Nectandra oppositifolia Nees & Mart. and assessment of antitrypanosomal activity of bioactive compounds through efficiency analyses

et al. 2021

View full text Add to dashboard Cite

EtOH extracts from the leaves and twigs of Nectandra oppositifolia Nees & Mart. shown activity against amastigote forms of Trypanosoma cruzi. These extracts were subjected to successive liquid-liquid partitioning to afford bioactive CH2Cl2 fractions. UHPLC-TOF-HRMS/MS and molecular networking were used to obtain an overview of the phytochemical composition of these active fractions. Aiming to isolate the active compounds, both CH2Cl2 fractions were subjected to fractionation using medium pressure chromatography combined with semi-preparative HPLC-UV. Using this approach, twelve compounds (1–12) were isolated and identified by NMR and HRMS analysis. Several isolated compounds displayed activity against the amastigote forms of T. cruzi, especially ethyl protocatechuate (7) with EC50 value of 18.1 μM, similar to positive control benznidazole (18.7 μM). Considering the potential of compound 7, protocatechuic acid and its respective methyl (7a), n-propyl (7b), n-butyl (7c), n-pentyl (7d), and n-hexyl (7e) esters were tested. Regarding antitrypanosomal activity, protocatechuic acid and compound 7a were inactive, while 7b-7e exhibited EC50 values from 20.4 to 11.7 μM, without cytotoxicity to mammalian cells. These results suggest that lipophilicity and molecular complexity play an important role in the activity while efficiency analysis indicates that the natural compound 7 is a promising prototype for further modifications to obtain compounds effective against the intracellular forms of T. cruzi.

show abstract

Secondary Metabolites and Antifungal Activity of the Endophytic Fungus Streptomyces humidus SCB0232 from Water Chestnut

Zhou

Jiang

et al. 2022

Chem Nat Compd

View full text Add to dashboard Cite

Isolation of Indole-3-Aldehyde As a Growth Inhibitor of Legionella pneumophila from Diaion HP-20 Resins Used to Culture the Bacteria

Cited by 6 publications

References 5 publications

Ammonia generation by tryptophan synthase drives a key genetic difference between genital and ocular Chlamydia trachomatis isolates

Ammonia generation by tryptophan synthase drives a key genetic difference between genital and ocular Chlamydia trachomatis isolates

Metabolite profile of Nectandra oppositifolia Nees & Mart. and assessment of antitrypanosomal activity of bioactive compounds through efficiency analyses

Secondary Metabolites and Antifungal Activity of the Endophytic Fungus Streptomyces humidus SCB0232 from Water Chestnut

Contact Info

Product

Resources

About