Physiological Studies of
            <i>Chlorobiaceae</i>
            Suggest that Bacillithiol Derivatives Are the Most Widespread Thiols in Bacteria

Hiras, Jennifer; Sharma, Sunil V.; Raman, Vidhyavathi; Tinson, Ryan; Arbach, Miriam; Rodrigues, Dominic; Norambuena, Javiera; Hamilton, Chris J.; Hanson, Thomas E.

doi:10.1128/mbio.01603-18

Cited by 15 publications

(20 citation statements)

References 60 publications

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“…Now, Hiras and colleagues report the identification and characterization of a novel thiol from the green sulfur bacterium Chlorobium tepidum (15). Like Chromatium sp., Chlorobia perform anoxygenic photosynthesis, oxidizing reduced sulfur compounds for CO 2 fixation and are obligate anaerobes.…”

Section: Commentarymentioning

confidence: 99%

“…Chlorobia and Chloroflexus dominate the H 2 S-containing geothermal environments found in areas such as Mammoth hot springs in Yellowstone National Park. Hiras et al (15) report that C. tepidum, Chlorobium phaeobacterioides, and Prosthecochloris sp.…”

Section: Commentarymentioning

confidence: 99%

“…Hiras and colleagues (15) also searched complete genome sequences with the BSH biosynthesis genes bshA , bshB, and bshC as well as nmbA for bacteria that could potentially produce BSH or N-Me-BSH. Orthologs of nmb A along with genes involved in BSH production were found in a representative Chlamyidae (Waddia chondrophila), Bacteriodetes ( Polaribacter sp.…”

Section: Commentarymentioning

confidence: 99%

“…The remaining bacteria have the potential to produce N-Me-BSH but await validation. Hiras et al (15) identified orthologs of nmbA in the phylum Clostridia ; however, the Clostridia phylogeny has recently undergone a major reevaluation based on whole-genome sequences (18). The strains identified as Clostridia by Hiras et al have been reclassified and are closer in lineage with the Chlorobia , and thus, the distribution of N-Me-BSH is not as wide as asserted.…”

Section: Commentarymentioning

confidence: 99%

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N-methyl-bacillithiol, a Novel Thiol from Anaerobic Bacteria

Newton

Rawat

2019

mBio

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J. Hiras, S. V. Sharma, V. Raman, R. A. J. Tinson, et al. (mBio 9:e01603-18, 2018, https://doi.org/10.1128/mBio.01603-18) report on the identification of a novel thiol, N-methyl-bacillithiol (N-Me-BSH), in the green sulfur bacterium Chlorobium tepidum. In N-methyl-bacillithiol, the amine of the cysteine is methylated by a novel S-adenosylmethioneine transferase designated N-methyl-bacillithiol synthase A (NmbA). The Hiras et al. study is significant because it is the first report of the presence of N-Me-BSH in anaerobic bacteria.

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Section: Commentarymentioning

confidence: 99%

Section: Commentarymentioning

confidence: 99%

Section: Commentarymentioning

confidence: 99%

Section: Commentarymentioning

confidence: 99%

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N-methyl-bacillithiol, a Novel Thiol from Anaerobic Bacteria

Newton

Rawat

2019

mBio

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“…A recent study identified a BSH derivative with an N-methylated cysteine as N-methyl-BSH in anaerobic phototrophic Chlorobiaceae, suggesting that BSH derivatives are more widely distributed and not restricted to Gram-positive firmicutes (Hiras et al, 2018). In S. aureus and Bacillus subtilis, BSH was characterized as cofactor of thiol-S-transferases (e.g.…”

Section: Introductionmentioning

confidence: 99%

Staphylococcus aureususes the bacilliredoxin (BrxAB)/ bacillithiol disulfide reductase (YpdA) redox pathway to defend against oxidative stress under infections

Linzner

Loi

Fritsch

et al. 2019

Preprint

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Staphylococcus aureus is a major human pathogen and has to cope with reactive oxygen and chlorine species (ROS, RCS) during infections. The low molecular weight thiol bacillithiol (BSH) is an important defense mechanism of S. aureus for detoxification of ROS and HOCl stress to maintain the reduced state of the cytoplasm. Under HOCl stress, BSH forms mixed disulfides with proteins, termed as S-bacillithiolations, which are reduced by bacilliredoxins (BrxA and BrxB). The NADPH-dependent flavin disulfide reductase YpdA is phylogenetically associated with the BSH synthesis and BrxA/B enzymes and was proposed to function as BSSB reductase. Here, we investigated the role of the bacilliredoxin BrxAB/BSH/YpdA pathway in S. aureus COL under oxidative stress and macrophage infection conditions in vivo and in biochemical assays in vitro. Using HPLC thiol metabolomics, a strongly enhanced BSSB level and a decreased BSH/BSSB ratio were measured in the S. aureus COL ypdA deletion mutant under control and NaOCl stress. Monitoring the BSH redox potential (E BSH) using the Brx-roGFP2 biosensor revealed that YpdA is required for regeneration of the reduced EBSH upon recovery from oxidative stress. In addition, the ypdA mutant was impaired in H2O2 detoxification as measured with the novel H2O2-specific Tpx-roGFP2 biosensor. Phenotype analyses further showed that BrxA and YpdA are required for survival under NaOCl and H2O2 stress in vitro and inside murine J-774A.1 macrophages in infection assays in vivo. Finally, NADPH-coupled electron transfer assays provide evidence for the function of YpdA in BSSB reduction, which depends on the conserved Cys14 residue. YpdA acts together with BrxA and BSH in de-bacillithiolation of S-bacilithiolated GapDH. In conclusion, our results point to a major role of the BrxA/BSH/YpdA pathway in BSH redox homeostasis in S. aureus during recovery from oxidative stress and under infections. * *

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In vitro study on the potential fungicidal effects of atorvastatin in combination with some azole drugs against multidrug resistant Candida albicans

Mahmoud

Faraag

El-Wafa

2021

World J Microbiol Biotechnol

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The resistance of Candida albicans to azole drugs represents a great global challenge. This study investigates the potential fungicidal effects of atorvastatin (ATO) combinations with fluconazole (FLU), itraconazole (ITR), ketoconazole (KET) and voriconazole (VOR) against thirty-four multidrug-resistant (MDR) C. albicans using checkerboard and time-kill methods. Results showed that 94.12% of these isolates were MDR to ≥ two azole drugs, whereas 5.88% of them were susceptible to azole drugs. The tested isolates exhibited high resistance rates to FLU (58.82%), ITR (52.94%), VOR (47.06%) and KET (35.29%), whereas only three representative (8.82%) isolates were resistant to all tested azoles. Remarkably, the inhibition zones of these isolates were increased at least twofold with the presence of ATO, which interacted in a synergistic (FIC index ≤ 0.5) manner with tested azoles. In silico docking study of ATO and the four azole drugs were performed against the Lanosterol 14-alpha demethylase enzyme (ERG11) of C. albicans . Results showed that the mechanism of action of ATO against C. albicans is similar to that of azole compounds, with a docking score (−4.901) lower than azole drugs (≥5.0) due to the formation a single H-bond with Asp 225 and a pi–pi interaction with Thr 229. Importantly, ATO combinations with ITR, VOR and KET achieved fungicidal effects (≥ 3 Log 10 cfu/ml reduction) against the representative isolates, whereas a fungistatic effect (≤ 3 Log 10 cfu/ml reduction) was observed with FLU combination. Thus, the combination of ATO with azole drugs could be promising options for treating C. albicans infection.

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Physiological Studies of Chlorobiaceae Suggest that Bacillithiol Derivatives Are the Most Widespread Thiols in Bacteria

Cited by 15 publications

References 60 publications

N-methyl-bacillithiol, a Novel Thiol from Anaerobic Bacteria

N-methyl-bacillithiol, a Novel Thiol from Anaerobic Bacteria

Staphylococcus aureususes the bacilliredoxin (BrxAB)/ bacillithiol disulfide reductase (YpdA) redox pathway to defend against oxidative stress under infections

In vitro study on the potential fungicidal effects of atorvastatin in combination with some azole drugs against multidrug resistant Candida albicans

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