title: Role of the carboxy terminus of SecA in iron acquisition, protein translocation, and virulence of the bacterial pathogen Acinetobacter baumannii.
abstract: Acinetobacter baumannii is a Gram-negative opportunistic nosocomial pathogen that causes pneumonia and soft tissue and systemic infections. Screening of a transposon insertion library of A. baumannii ATCC 19606T resulted in the identification of the 2010 derivative, which, although capable of growing well in iron-rich media, failed to prosper under iron chelation. Genetic, molecular, and functional assays showed that 2010's iron utilization-deficient phenotype is due to an insertion within the 3' end of secA, which results in the production of a C-terminally truncated derivative of SecA. SecA plays a critical role in protein translocation through the SecYEG membrane channel. Accordingly, the secA mutation resulted in undetectable amounts of the ferric acinetobactin outer membrane receptor protein BauA while not affecting the production of other acinetobactin membrane protein transport components, such as BauB and BauE, or the secretion of acinetobactin by 2010 cells cultured in the presence of subinhibitory concentrations of the synthetic iron chelator 2,2'-dipyridyl. Outer membrane proteins involved in nutrient transport, adherence, and biofilm formation were also reduced in 2010. The SecA truncation also increased production of 30 different proteins, including proteins involved in adaptation/tolerance responses. Although some of these protein changes could negatively affect the pathobiology of the 2010 derivative, its virulence defect is mainly due to its inability to acquire iron via the acinetobactin-mediated system. These results together indicate that although the C terminus of the A. baumannii ATCC 19606T SecA is not essential for viability, it plays a critical role in the production and translocation of different proteins and virulence.
authors.affiliation: Department of Microbiology, Miami University, Oxford, Ohio, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Fiester
authors.affiliation: Department of Microbiology, Miami University, Oxford, Ohio, USA.
authors.forename: Chika C
authors.initials: CC
authors.lastname: Nwugo
authors.affiliation: Department of Microbiology, Miami University, Oxford, Ohio, USA.
authors.forename: William F
authors.initials: WF
authors.lastname: Penwell
authors.affiliation: Department of Microbiology, Miami University, Oxford, Ohio, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Neary
authors.affiliation: Department of Microbiology, Miami University, Oxford, Ohio, USA.
authors.forename: Amber C
authors.initials: AC
authors.lastname: Beckett
authors.affiliation: Department of Microbiology, Miami University, Oxford, Ohio, USA.
authors.forename: Brock A
authors.initials: BA
authors.lastname: Arivett
authors.affiliation: Department of Microbiology, Miami University, Oxford, Ohio, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Schmidt
authors.affiliation: Department of Microbiology, Miami University, Oxford, Ohio, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Geiger
authors.affiliation: Department of Microbiology, Miami University, Oxford, Ohio, USA.
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Connerly
authors.affiliation: Department of Microbiology, Miami University, Oxford, Ohio, USA.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Menke
authors.affiliation: Department of Microbiology, Miami University, Oxford, Ohio, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Tomaras
authors.affiliation: Department of Microbiology, Miami University, Oxford, Ohio, USA actisla@MiamiOH.edu.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Actis
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry; D000151:Acinetobacter Infections / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D007093:Imidazoles / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism; D007501:Iron / Q000737:chemistry / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009036:Moths / Q000382:microbiology; D009154:Mutation; D010080:Oxazoles / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D000069816:SEC Translocation Channels; D000081416:SecA Proteins; D037521:Virulence Factors / Q000235:genetics
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D007093:Imidazoles; D007473:Ion Channels; D026901:Membrane Transport Proteins; D010080:Oxazoles; D000069816:SEC Translocation Channels; D037521:Virulence Factors; C091186:acinetobactin; D015082:2,2'-Dipyridyl; D007501:Iron; D000251:Adenosine Triphosphatases; D000081416:SecA Proteins