title: Clostridiolysin S, a post-translationally modified biotoxin from Clostridium botulinum.
abstract: Through elaboration of its botulinum toxins, Clostridium botulinum produces clinical syndromes of infant botulism, wound botulism, and other invasive infections. Using comparative genomic analysis, an orphan nine-gene cluster was identified in C. botulinum and the related foodborne pathogen Clostridium sporogenes that resembled the biosynthetic machinery for streptolysin S, a key virulence factor from group A Streptococcus responsible for its hallmark beta-hemolytic phenotype. Genetic complementation, in vitro reconstitution, mass spectral analysis, and plasmid intergrational mutagenesis demonstrate that the streptolysin S-like gene cluster from Clostridium sp. is responsible for the biogenesis of a novel post-translationally modified hemolytic toxin, clostridiolysin S.
authors.affiliation: Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Gonzalez
authors.forename: Shaun W
authors.initials: SW
authors.lastname: Lee
authors.forename: Mary E
authors.initials: ME
authors.lastname: Hensler
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Markley
authors.forename: Samira
authors.initials: S
authors.lastname: Dahesh
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Mitchell
authors.forename: Nuno
authors.initials: N
authors.lastname: Bandeira
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
authors.forename: Jack E
authors.initials: JE
authors.lastname: Dixon
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dorrestein
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001905:Botulinum Toxins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002853:Chromatography, Liquid; D003014:Clostridium botulinum / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology; D005816:Genetic Complementation Test; D056426:Genetic Loci / Q000235:genetics; D023281:Genomics; D006461:Hemolysis; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D009876:Operon / Q000235:genetics; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D013297:Streptococcus pyogenes / Q000235:genetics; D013301:Streptolysins / Q000235:genetics / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D037521:Virulence Factors / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D010446:Peptide Fragments; D011498:Protein Precursors; D013301:Streptolysins; D037521:Virulence Factors; C026050:streptolysin S; D001905:Botulinum Toxins