scholarly journals Physiological Studies ofChlorobiaceaeSuggest that Bacillithiol Derivatives Are the Most Widespread Thiols in Bacteria

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Jennifer Hiras ◽  
Sunil V. Sharma ◽  
Vidhyavathi Raman ◽  
Ryan A. J. Tinson ◽  
Miriam Arbach ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Redox Homeostasis ◽  
Genomic Analysis ◽  
Sulfur Oxidation ◽  
Comparative Genomic ◽  
Low Molecular Weight ◽  
Molecular Formula ◽  
Gram Positive ◽  
Content Type ◽  
Gram Positive Bacteria

ABSTRACTLow-molecular-weight (LMW) thiols mediate redox homeostasis and the detoxification of chemical stressors. Despite their essential functions, the distribution of LMW thiols across cellular life has not yet been defined. LMW thiols are also thought to play a central role in sulfur oxidation pathways in phototrophic bacteria, including theChlorobiaceae. Here we show thatChlorobaculum tepidumsynthesizes a novel LMW thiol with a mass of 412 ± 1 Da corresponding to a molecular formula of C14H24N2O10S, which suggests that the new LMW thiol is closely related to bacillithiol (BSH), the major LMW thiol of low-G+C Gram-positive bacteria. TheCba. tepidumLMW thiol structure was N-methyl-bacillithiol (N-Me-BSH), methylated on the cysteine nitrogen, the fourth instance of this modification in metabolism. Orthologs of bacillithiol biosynthetic genes in theCba. tepidumgenome and the CT1040 gene product, N-Me-BSH synthase, were required for N-Me-BSH synthesis. N-Me-BSH was found in allChlorobiaceaeexamined as well asPolaribactersp. strain MED152, a member of theBacteroidetes. A comparative genomic analysis indicated that BSH/N-Me-BSH is synthesized not only by members of theChlorobiaceae,Bacteroidetes,Deinococcus-Thermus, andFirmicutesbut also byAcidobacteria,Chlamydiae,Gemmatimonadetes, andProteobacteria.Thus, BSH and derivatives appear to be the most broadly distributed LMW thiols in biology.IMPORTANCELow-molecular-weight thiols are key metabolites that participate in many basic cellular processes: central metabolism, detoxification, and oxidative stress resistance. Here we describe a new thiol, N-methyl-bacillithiol, found in an anaerobic phototrophic bacterium and identify a gene that is responsible for its synthesis from bacillithiol, the main thiol metabolite in many Gram-positive bacteria. We show that the presence or absence of this gene in a sequenced genome accurately predicts thiol content in distantly related bacteria. On the basis of these results, we analyzed genome data and predict that bacillithiol and its derivatives are the most widely distributed thiol metabolites in biology.

scholarly journals N-methyl-bacillithiol, a new metabolite discovered in theChlorobiaceae, indicates that bacillithiol and derivatives are widely phylogenetically distributed

2017 ◽  
Author(s):  
Jennifer Hiras ◽  
Sunil V. Sharma ◽  
Vidhyavathi Raman ◽  
Ryan A. J. Tinson ◽  
Miriam Arbach ◽  
...  
Keyword(s):  
Redox Homeostasis ◽  
Genomic Analysis ◽  
Sulfur Oxidation ◽  
Comparative Genomic ◽  
Molecular Formula ◽  
Gram Positive Bacteria ◽  
Redox Responsive ◽  
Functional Consequences

AbstractLow-molecular weight (LMW) thiols are metabolites that mediate redox homeostasis and the detoxification of chemical stressors in cells. LMW thiols are also thought to play a central role in sulfur oxidation pathways in phototrophic bacteria, including theChlorobiaceae. Fluorescent thiol labeling of metabolite extracts coupled with HPLC showed thatChlorobaculum tepidumcontained a novel LMW thiol with a mass of 412 ± 1 Da corresponding to a molecular formula of C14H24N2O10S. These data suggested the new thiol is closely related to bacillithiol (BSH), the major LMW thiol from low G+C% Gram-positive bacteria. By comparing the as-isolated bimane adduct with chemically synthesized candidate structures, theCba. tepidumthiol structure was identified as N-methyl-bacillithiol (N-Me-BSH), methylated on the cysteine nitrogen, a rarely observed modification in metabolism. Orthologs of bacillithiol biosynthetic genes in theCba. tepidumgenome were required for the biosynthesis of N-Me-BSH. Furthermore, the CT1040 gene product was genetically identified as the BSH N-methyltransferase. N-Me-BSH was found in allChlorobiexamined as well asPolaribactersp. strain MED152, a member of theBacteroidetes.A comparative genomic analysis indicated that BSH/N-Me-BSH is synthesized not only by members of theChlorobi,Bacteroidetes,Deinococcus-Thermus, andFirmicutes, but also byAcidobacteria,Chlamydiae,Gemmatimonadetes, andProteobacteria.Significance StatementHere, N-Me-BSH is shown to be a redox-responsive LMW thiol cofactor inCba. tepidumand the gene,nmbA, encoding the BSH N-methyltransferase responsible for its synthesis is identified. The co-occurrence of orthologs to BSH biosynthesis genes and bacillithiol N-methyltransferase was confirmed to correctly predict LMW thiol biosynthesis in phylogenetically distant genomes. The analysis indicates that BSH/N-Me-BSH are likely the most widely distributed class of LMW thiols in biology. This finding sheds light on the evolution of LMW thiol metabolism, which is central to redox homeostasis, regulation and stress resistance in all cellular life. It also sheds light on a rare chemical modification. N-Me-BSH is the fourth instance of cysteinyl nitrogen methylation in metabolism. Identification of the BSH N-methyltransferase reported here will enable detailedin vivoandin vitrodissection of the functional consequences of this modification. As a standalone N-methyltransferase, NmbA may be useful as a component of constructed biosynthetic pathways for novel product (bio)synthesis.

Chemical and Chemoenzymatic Syntheses of Bacillithiol: A Unique Low-Molecular-Weight Thiol amongst Low G + C Gram-Positive Bacteria

2011 ◽  
Vol 50 (31) ◽  
pp. 7101-7104 ◽  
Author(s):  
Sunil V. Sharma ◽  
Vishnu K. Jothivasan ◽  
Gerald L. Newton ◽  
Heather Upton ◽  
Judy I. Wakabayashi ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight ◽  
Gram Positive ◽  
Gram Positive Bacteria

scholarly journals Closing Clostridium botulinum Group III Genomes Using Long-Read Sequencing

2021 ◽  
Vol 10 (22) ◽  
Author(s):  
Cedric Woudstra ◽  
Tommi Mäklin ◽  
Yagmur Derman ◽  
Luca Bano ◽  
Hanna Skarin ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Clostridium Botulinum ◽  
Gram Positive ◽  
High Molecular Weight Dna ◽  
Content Type ◽  
Group Iii ◽  
Gram Positive Bacteria ◽  
Complete Genomes ◽  
Long Read

Clostridium botulinum group III is the anaerobic Gram-positive bacteria producing the deadly neurotoxin responsible for animal botulism. Here, we used long-read sequencing to produce four complete genomes from Clostridium botulinum group III neurotoxin types C, D, C/D, and D/C. The protocol to obtain high-molecular-weight DNA from C. botulinum group III is described.

Chemical and Chemoenzymatic Syntheses of Bacillithiol: A Unique Low-Molecular-Weight Thiol amongst Low G + C Gram-Positive Bacteria

2011 ◽  
Vol 123 (31) ◽  
pp. 7239-7242 ◽  
Author(s):  
Sunil V. Sharma ◽  
Vishnu K. Jothivasan ◽  
Gerald L. Newton ◽  
Heather Upton ◽  
Judy I. Wakabayashi ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight ◽  
Gram Positive ◽  
Gram Positive Bacteria

scholarly journals Low-Molecular-Weight Metabolites Secreted by Paenibacillus larvae as Potential Virulence Factors of American Foulbrood

2014 ◽  
Vol 80 (8) ◽  
pp. 2484-2492 ◽  
Author(s):  
Hedwig-Annabell Schild ◽  
Sebastian W. Fuchs ◽  
Helge B. Bode ◽  
Bernd Grünewald
Keyword(s):  
Molecular Weight ◽  
Virulence Factors ◽  
Gene Clusters ◽  
Paenibacillus Larvae ◽  
Economic Losses ◽  
Low Molecular Weight ◽  
American Foulbrood ◽  
Toxic Activity ◽  
Content Type

ABSTRACTThe spore-forming bacteriumPaenibacillus larvaecauses a severe and highly infective bee disease, American foulbrood (AFB). Despite the large economic losses induced by AFB, the virulence factors produced byP. larvaeare as yet unknown. To identify such virulence factors, we experimentally infected young, susceptible larvae of the honeybee,Apis mellifera carnica, with differentP. larvaeisolates. Honeybee larvae were rearedin vitroin 24-well plates in the laboratory after isolation from the brood comb. We identified genotype-specific differences in the etiopathology of AFB between the tested isolates ofP. larvae, which were revealed by differences in the median lethal times. Furthermore, we confirmed that extracts ofP. larvaecultures contain low-molecular-weight compounds, which are toxic to honeybee larvae. Our data indicate thatP. larvaesecretes metabolites into the medium with a potent honeybee toxic activity pointing to a novel pathogenic factor(s) ofP. larvae. Genome mining ofP. larvaesubsp.larvaeBRL-230010 led to the identification of several biosynthesis gene clusters putatively involved in natural product biosynthesis, highlighting the potential ofP. larvaeto produce such compounds.

scholarly journals Antimicrobial Nodule-Specific Cysteine-Rich Peptides Induce Membrane Depolarization-Associated Changes in the Transcriptome of Sinorhizobium meliloti

2013 ◽  
Vol 79 (21) ◽  
pp. 6737-6746 ◽  
Author(s):  
Hilda Tiricz ◽  
Attila Szűcs ◽  
Attila Farkas ◽  
Bernadett Pap ◽  
Rui M. Lima ◽  
...  
Keyword(s):  
Stress Responses ◽  
Sinorhizobium Meliloti ◽  
Antimicrobial Agents ◽  
Cellular Functions ◽  
Gram Positive ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Peptide Family ◽  
Wide Range ◽  
Natural Target

ABSTRACTLeguminous plants establish symbiosis with nitrogen-fixing alpha- and betaproteobacteria, collectively called rhizobia, which provide combined nitrogen to support plant growth. Members of the inverted repeat-lacking clade of legumes impose terminal differentiation on their endosymbiotic bacterium partners with the help of the nodule-specific cysteine-rich (NCR) peptide family composed of close to 600 members. Among the few tested NCR peptides, cationic ones had antirhizobial activity measured by reduction or elimination of the CFU and uptake of the membrane-impermeable dye propidium iodide. Here, the antimicrobial spectrum of two of these peptides, NCR247 and NCR335, was investigated, and their effect on the transcriptome of the natural targetSinorhizobium melilotiwas characterized. Both peptides were able to kill quickly a wide range of Gram-negative and Gram-positive bacteria; however, their spectra were only partially overlapping, and differences were found also in their efficacy on given strains, indicating that the actions of NCR247 and NCR335 might be similar though not identical. Treatment ofS. meliloticultures with either peptide resulted in a quick downregulation of genes involved in basic cellular functions, such as transcription-translation and energy production, as well as upregulation of genes involved in stress and oxidative stress responses and membrane transport. Similar changes provoked mainly in Gram-positive bacteria by antimicrobial agents were coupled with the destruction of membrane potential, indicating that it might also be a common step in the bactericidal actions of NCR247 and NCR335.

scholarly journals Restoration of Bioactive Lantibiotic Suicin from a RemnantlanLocus of Pathogenic Streptococcus suis Serotype 2

2013 ◽  
Vol 80 (3) ◽  
pp. 1062-1071 ◽  
Author(s):  
Jian Wang ◽  
Yong Gao ◽  
Kunling Teng ◽  
Jie Zhang ◽  
Shutao Sun ◽  
...  
Keyword(s):  
Gene Promoter ◽  
Streptococcus Suis ◽  
Gene Clusters ◽  
Disulfide Bridge ◽  
Gram Positive ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
System A ◽  
Bactericidal Activities

ABSTRACTLantibiotics are ribosomally synthesized, posttranslationally modified antimicrobial peptides. Their biosynthesis genes are usually organized in gene clusters, which are mainly found in Gram-positive bacteria, including pathogenic streptococci. Three highly virulentStreptococcus suisserotype 2 strains (98HAH33, 05ZYH33, and SC84) have been shown to contain an 89K pathogenicity island. Here, on these islands, we unveiled and reannotated a putative lantibiotic locus designatedsuiwhich contains a virulence-associated two-component regulator,suiK-suiR. In silicoanalysis revealed that the putative lantibiotic modification genesuiMwas interrupted by a 7.9-kb integron and that other biosynthesis-related genes contained various frameshift mutations. By reconstituting the intactsuiMinEscherichia colitogether with a semi-in vitrobiosynthesis system, a putative lantibiotic named suicin was produced with bactericidal activities against a variety of Gram-positive strains, including pathogenic streptococci and vancomycin-resistant enterococci. Ring topology dissection indicated that the 34-amino-acid lantibiotic contained two methyllanthionine residues and one disulfide bridge, which render suicin in an N-terminal linear and C-terminal globular shape. To confirm the function ofsuiK-suiR, SuiR was overexpressed and purified.In vitroanalysis showed that SuiR could specifically bind to thesuiAgene promoter. Its coexpression withsuiKcould activatesuiAgene promoter inLactococcus lactisNZ9000. Conclusively, we obtained a novel lantibiotic suicin by restoring its production from the remnantsuilocus and demonstrated that virulence-associated SuiK-SuiR regulates its production.

scholarly journals Genomic Analysis of Multiresistant Staphylococcus capitis Associated with Neonatal Sepsis

2018 ◽  
Vol 62 (11) ◽  
Author(s):  
Glen P. Carter ◽  
James E. Ussher ◽  
Anders Gonçalves Da Silva ◽  
Sarah L. Baines ◽  
Helen Heffernan ◽  
...  
Keyword(s):  
Neonatal Sepsis ◽  
Neonatal Intensive Care ◽  
Genomic Analysis ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Comparative Genomic ◽  
Coagulase Negative Staphylococci ◽  
Content Type ◽  
Staphylococcus Capitis ◽  
Hospital Infection Control

ABSTRACT Coagulase-negative staphylococci (CoNS), such as Staphylococcus capitis, are major causes of bloodstream infections in neonatal intensive care units (NICUs). Recently, a distinct clone of S. capitis (designated S. capitis NRCS-A) has emerged as an important pathogen in NICUs internationally. Here, 122 S. capitis isolates from New Zealand (NZ) underwent whole-genome sequencing (WGS), and these data were supplemented with publicly available S. capitis sequence reads. Phylogenetic and comparative genomic analyses were performed, as were phenotypic assessments of antimicrobial resistance, biofilm formation, and plasmid segregational stability on representative isolates. A distinct lineage of S. capitis was identified in NZ associated with neonates and the NICU environment. Isolates from this lineage produced increased levels of biofilm, displayed higher levels of tolerance to chlorhexidine, and were multidrug resistant. Although similar to globally circulating NICU-associated S. capitis strains at a core-genome level, NZ NICU S. capitis isolates carried a novel stably maintained multidrug-resistant plasmid that was not present in non-NICU isolates. Neonatal blood culture isolates were indistinguishable from environmental S. capitis isolates found on fomites, such as stethoscopes and neonatal incubators, but were generally distinct from those isolates carried by NICU staff. This work implicates the NICU environment as a potential reservoir for neonatal sepsis caused by S. capitis and highlights the capacity of genomics-based tracking and surveillance to inform future hospital infection control practices aimed at containing the spread of this important neonatal pathogen.

scholarly journals Complete Genome Resequencing of Thermus thermophilus Strain TMY by Hybrid Assembly of Long- and Short-Read Sequencing Technologies

2021 ◽  
Vol 10 (46) ◽  
Author(s):  
Kentaro Miyazaki ◽  
Natsuko Tokito
Keyword(s):  
Complete Genome ◽  
Thermus Thermophilus ◽  
Genomic Analysis ◽  
Comparative Genomic ◽  
Hybrid Assembly ◽  
Genome Resequencing ◽  
Short Read ◽  
Content Type ◽  
Sequencing Technologies ◽  
Long Read

Complete genome resequencing was conducted for Thermus thermophilus strain TMY by hybrid assembly of Oxford Nanopore Technologies long-read and MGI short-read data. Errors in the previously reported genome sequence determined by PacBio technology alone were corrected, allowing for high-quality comparative genomic analysis of closely related T. thermophilus genomes.

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