title: PathogenicAcinetobacterspecies have a functional type I secretion system and contact-dependent inhibition systems.
abstract: PathogenicAcinetobacterspecies, includingAcinetobacter baumanniiandAcinetobacter nosocomialis, are opportunistic human pathogens of increasing relevance worldwide. Although their mechanisms of drug resistance are well studied, the virulence factors that governAcinetobacterpathogenesis are incompletely characterized. Here we define the complete secretome ofA. nosocomialisstrain M2 in minimal medium and demonstrate that pathogenicAcinetobacterspecies produce both a functional type I secretion system (T1SS) and a contact-dependent inhibition (CDI) system. Using bioinformatics, quantitative proteomics, and mutational analyses, we show thatAcinetobacteruses its T1SS for exporting two putative T1SS effectors, an Repeats-in-Toxin (RTX)-serralysin-like toxin, and the biofilm-associated protein (Bap). Moreover, we found that mutation of any component of the T1SS system abrogated type VI secretion activity under nutrient-limited conditions, indicating a previously unrecognized cross-talk between these two systems. We also demonstrate that theAcinetobacterT1SS is required for biofilm formation. Last, we show that bothA. nosocomialisandA. baumanniiproduce functioning CDI systems that mediate growth inhibition of sister cells lacking the cognate immunity protein. TheAcinetobacterCDI systems are widely distributed across pathogenicAcinetobacterspecies, with manyA. baumanniiisolates harboring two distinct CDI systems. Collectively, these data demonstrate the power of differential, quantitative proteomics approaches to study secreted proteins, define the role of previously uncharacterized protein export systems, and observe cross-talk between secretion systems in the pathobiology of medically relevantAcinetobacterspecies.
authors.affiliation: From the Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Harding
authors.affiliation: From the Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110.|the Unit of Infectious Diseases, Microbiology, and Preventive Medicine and Biomedical Institute of Seville, University Hospital Virgen del Rocío/Consejo Superior de Investigaciones Científicas, University of Sevilla, 41004 Seville, Spain.
authors.forename: Marina R
authors.initials: MR
authors.lastname: Pulido
authors.affiliation: From the Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Gisela
authors.initials: G
authors.lastname: Di Venanzio
authors.affiliation: From the Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110.|the Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2R3, Canada.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Kinsella
authors.affiliation: the Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria 3052, Australia.|the Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia, and.
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Webb
authors.affiliation: the Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Nichollas E
authors.initials: NE
authors.lastname: Scott
authors.affiliation: the Unit of Infectious Diseases, Microbiology, and Preventive Medicine and Biomedical Institute of Seville, University Hospital Virgen del Rocío/Consejo Superior de Investigaciones Científicas, University of Sevilla, 41004 Seville, Spain.
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Pachón
authors.affiliation: From the Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, mariofeldman@wustl.edu.
authors.forename: Mario F
authors.initials: MF
authors.lastname: Feldman
mesh_terms: D040981:Acinetobacter baumannii / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D058947:Bacterial Secretion Systems / Q000235:genetics / Q000378:metabolism*; D006801:Humans
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems
keywords: Acinetobacter; bacterial pathogenesis; bacterial toxin; biofilm; contact-dependent inhibition system; protein secretion; proteomics; type I secretion system