Clostridiolysin S, a post-translationally modified biotoxin from Clostridium botulinum.
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.
Gonzalez
David J
DJ
Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093, USA.
Lee
Shaun W
SW
Hensler
Mary E
ME
Markley
Andrew L
AL
Dahesh
Samira
S
Mitchell
Douglas A
DA
Bandeira
Nuno
N
Nizet
Victor
V
Dixon
Jack E
JE
Dorrestein
Pieter C
PC
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
D001426:Bacterial Proteins; D010446:Peptide Fragments; D011498:Protein Precursors; D013301:Streptolysins; D037521:Virulence Factors; C026050:streptolysin S; D001905:Botulinum Toxins