Thiotropocin, a new sulfur-containing 7-membered-ring antibiotic produced by a Pseudomonas sp.

Kintaka, Kazuhiko; Onο, Hideo; Tsubotani, Shigetoshi; Harada, Setsuo; Okazaki, Hiroyuki

doi:10.7164/antibiotics.37.1294

Cited by 46 publications

(44 citation statements)

References 8 publications

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“…S1 in the supplemental material). MIC values for S. Typhimurium SL1344, E. coli NCTC 10535, P. aeruginosa NCTC 10662, S. aureus NCTC 8532, and V. anguillarum 90-11-287 were 3 to 25 mg/liter when using pure TDA, which is in the same range as those reported previously for thiotropocin (26), which is considered a tautomer of TDA (21).…”

Section: Resultssupporting

confidence: 73%

“…None of the porin or efflux pump mutants of S. Typhimurium had major altered tolerance to TDA extract compared with their parental strains. Kintaka et al previously reported MIC values of thiotropocin for human-pathogenic bacteria that were lower than those found in the present work (26). Kintaka et al purified TDA from 1,200 liters of a Pseudomonas culture and did not specify the method used for MIC determinations.…”

Section: Resultscontrasting

confidence: 43%

“…and Pseudovibrio strains (15,25). It is antibacterial against several bacteria, including Escherichia coli and Pseudomonas aeruginosa (3,26,48). Tropolones with side groups other than a disulfide are also known to be antibacterial (32,33) and display antifungal and antiviral activities (7,26).…”

mentioning

confidence: 99%

“…TDA has antibacterial action against bacteria outside the marine or aquatic environment, including human-pathogenic bacteria (3,26,48), and could also be of interest as an antibacterial outside the aquaculture sector. However, a widespread use of TDA could be potentially detrimental if resistance and subsequent cross-resistance to other agents develop, as has been the case for the majority of drugs discovered so far (11).…”

mentioning

confidence: 99%

“…Thiotropocin (or tropodithietic acid) was first isolated from a soil bacterium identified as a Pseudomonas species (8,26), and in addition to Roseobacter clade bacteria, the compound has also been isolated from marine Caulobacter spp. and Pseudovibrio strains (15,25).…”

mentioning

confidence: 99%

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Resistance and Tolerance to Tropodithietic Acid, an Antimicrobial in Aquaculture, Is Hard To Select

Porsby

Webber

Nielsen

et al. 2011

Antimicrob Agents Chemother

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The antibacterial compound tropodithietic acid (TDA) is produced by bacteria of the marine Roseobacter clade and is thought to explain the fish probiotic properties of some roseobacters. The aim of the present study was to determine the antibacterial spectrum of TDA and the likelihood of development of TDA resistance. A bacterial extract containing 95% TDA was effective against a range of human-pathogenic bacteria, including both Gram-negative and Gram-positive bacteria. TDA was bactericidal against Salmonella enterica serovar Typhimurium SL1344 and Staphylococcus aureus NCTC 12493 and killed both growing and nongrowing cells. Several experimental approaches were used to select mutants resistant to TDA or subpopulations of strains with enhanced tolerance to TDA. No approach (single exposures to TDA extract administered via different methods, screening of a transposon library for resistant mutants, or prolonged exposure to incremental concentrations of TDA) resulted in resistant or tolerant strains. After more than 300 generations exposed to sub-MIC and MIC concentrations of a TDA-containing extract, strains tolerant to 2؋ the MIC of TDA for wild-type strains were selected, but the tolerance disappeared after one passage in medium without TDA extract. S. Typhimurium mutants with nonfunctional efflux pump and porin genes had the same TDA susceptibility as wild-type strains, suggesting that efflux pumps and porins are not involved in innate tolerance to TDA. TDA is a promising broad-spectrum antimicrobial in part due to the fact that enhanced tolerance is difficult to gain and that the TDA-tolerant phenotype appears to confer only low-level resistance and is very unstable.

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Section: Resultssupporting

confidence: 73%

Section: Resultscontrasting

confidence: 43%