title: A Salmonella Typhi homologue of bacteriophage muramidases controls typhoid toxin secretion.
abstract: Unlike other Salmonella, which can infect a broad range of hosts causing self-limiting infection, Salmonella Typhi is an exclusively human pathogen that causes typhoid fever, a life-threatening systemic disease. Typhoid toxin is a unique virulence factor of Salmonella Typhi, which is expressed when the bacteria are within mammalian cells. Here, we report that an N-acetyl-β-D-muramidase similar to phage endolysins encoded within the same pathogenicity islet as the toxin is required for typhoid toxin secretion. Genetic and functional analysis of TtsA revealed unique amino acids at its predicted peptidoglycan-binding domain that are essential for protein secretion and that distinguishes this protein from other homologues. We propose that TtsA defines a new protein secretion mechanism recently evolved from the machine that mediates phage release.
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
authors.forename: Hélène
authors.initials: H
authors.lastname: Hodak
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Galán
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001427:Bacterial Toxins / Q000378:metabolism*; D001435:Bacteriophages / Q000737:chemistry / Q000235:genetics; D002460:Cell Line; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D044404:Genomic Islands; D006801:Humans; D008969:Molecular Sequence Data; D009113:Muramidase / Q000235:genetics* / Q000378:metabolism; D012485:Salmonella typhi / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D014764:Viral Proteins; D009113:Muramidase; D010450:Endopeptidases; C001143:endolysin