title: Characterization of an autotransporter adhesin protein shared by Burkholderia mallei and Burkholderia pseudomallei.
abstract: BACKGROUND
  Autotransporters form a large family of outer membrane proteins specifying diverse biological traits of Gram-negative bacteria. In this study, we report the identification and characterization of a novel autotransporter gene product of Burkholderia mallei (locus tag BMA1027 in strain ATCC 23344).
  
  
  RESULTS
  Database searches identified the gene in at least seven B. mallei isolates and the encoded proteins were found to be 84% identical. Inactivation of the gene encoding the autotransporter in the genome of strain ATCC 23344 substantially reduces adherence to monolayers of HEp-2 laryngeal cells and A549 type II pneumocytes, as well as to cultures of normal human bronchial epithelium (NHBE). Consistent with these findings, expression of the autotransporter on the surface of recombinant E. coli bacteria increases adherence to these cell types by 5-7 fold. The gene specifying the autotransporter was identified in the genome of 29 B. pseudomallei isolates and disruption of the gene in strain DD503 reduced adherence to NHBE cultures by 61%. Unlike B. mallei, the mutation did not impair binding of B. pseudomallei to A549 or HEp-2 cells. Analysis of sera from mice infected via the aerosol route with B. mallei and B. pseudomallei revealed that animals inoculated with as few as 10 organisms produce antibodies against the autotransporter, therefore indicating expression in vivo.
  
  
  CONCLUSIONS
  Our data demonstrate that we have identified an autotransporter protein common to the pathogenic species B. mallei and B. pseudomallei which mediates adherence to respiratory epithelial cells and is expressed in vivo during the course of aerosol infection.
authors.affiliation: Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, 30602 Athens, GA, USA. elafon10@uga.edu.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Lafontaine
authors.forename: Rachel
authors.initials: R
authors.lastname: Balder
authors.forename: Frank
authors.initials: F
authors.lastname: Michel
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hogan
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D042726:Burkholderia mallei / Q000235:genetics / Q000502:physiology*; D016957:Burkholderia pseudomallei / Q000235:genetics / Q000502:physiology*; D004847:Epithelial Cells / Q000382:microbiology; D004926:Escherichia coli / Q000235:genetics / Q000502:physiology; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins; D026901:Membrane Transport Proteins; D011994:Recombinant Proteins
references.citation: J Bacteriol. 2001 Mar;183(5):1540-51
references.pmid: 11160084
references.citation: Infect Immun. 2004 Apr;72(4):1906-13
references.pmid: 15039309
references.citation: Front Microbiol. 2011 Jul 15;2:151
references.pmid: 21811486
references.citation: Harefuah. 2002 May;141 Spec No:88-91, 119
references.pmid: 12170562
references.citation: Infect Immun. 1987 Dec;55(12):2902-11
references.pmid: 2445682
references.citation: Front Cell Infect Microbiol. 2012 Dec 20;2:164
references.pmid: 23267442
references.citation: Mol Microbiol. 2005 Apr;56(1):40-53
references.pmid: 15773977
references.citation: Infect Immun. 2007 Jan;75(1):30-4
references.pmid: 17030570
references.citation: BMC Microbiol. 2007 Jul 03;7:65
references.pmid: 17608944
references.citation: BMC Microbiol. 2007 Mar 15;7:19
references.pmid: 17362501
references.citation: Infect Immun. 1999 Jun;67(6):2891-900
references.pmid: 10338496
references.citation: Infect Immun. 2005 Aug;73(8):5127-36
references.pmid: 16041029
references.citation: EMBO J. 2004 Feb 25;23(4):701-11
references.pmid: 14765110
references.citation: Expert Rev Vaccines. 2008 Nov;7(9):1357-65
references.pmid: 18980539
references.citation: Microbes Infect. 2000 Jul;2(9):1061-72
references.pmid: 10967286
references.citation: Infect Immun. 2004 Jul;72(7):4052-60
references.pmid: 15213150
references.citation: FEMS Microbiol Rev. 2009 Nov;33(6):1079-99
references.pmid: 19732156
references.citation: Infect Immun. 2009 Feb;77(2):632-41
references.pmid: 19029299
references.citation: Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):457-62
references.pmid: 24335802
references.citation: PLoS One. 2013 Oct 02;8(10):e76804
references.pmid: 24098563
references.citation: Infect Immun. 2008 Nov;76(11):5330-40
references.pmid: 18678659
references.citation: J Bacteriol. 2001 Nov;183(22):6717-20
references.pmid: 11673447
references.citation: Infect Immun. 2005 Apr;73(4):2400-10
references.pmid: 15784586
references.citation: Infect Immun. 2007 Jan;75(1):314-24
references.pmid: 17088358
references.citation: Trends Microbiol. 2005 May;13(5):199-205
references.pmid: 15866036
references.citation: Annu Rev Microbiol. 2010;64:495-517
references.pmid: 20528691
references.citation: Antimicrob Agents Chemother. 2010 Aug;54(8):3113-20
references.pmid: 20498323
references.citation: Vaccine. 2008 Aug 5;26(33):4244-50
references.pmid: 18582996
references.citation: Trends Microbiol. 1998 Sep;6(9):370-8
references.pmid: 9778731
references.citation: Emerg Infect Dis. 2012 Dec;18(12):e2
references.pmid: 23171644
references.citation: Trends Microbiol. 2006 Jun;14(6):264-70
references.pmid: 16678419
references.citation: BMC Microbiol. 2010 Sep 28;10:250
references.pmid: 20920184
references.citation: Infect Immun. 2013 Aug;81(8):2788-99
references.pmid: 23716608
references.citation: Clin Infect Dis. 2000 Oct;31(4):981-6
references.pmid: 11049780
references.citation: Infect Immun. 2009 Oct;77(10):4597-608
references.pmid: 19667048
references.citation: Infect Immun. 2008 Nov;76(11):5322-9
references.pmid: 18678656
references.citation: J Bacteriol. 2008 Jun;190(12):4147-61
references.pmid: 18424525
references.citation: Acta Trop. 2000 Feb 5;74(2-3):115-9
references.pmid: 10674638
references.citation: J Bacteriol. 2004 Dec;186(23):8058-65
references.pmid: 15547278
references.citation: Trans R Soc Trop Med Hyg. 2000 May-Jun;94(3):301-4
references.pmid: 10975006
references.citation: Mol Microbiol. 2004 Jan;51(1):283-96
references.pmid: 14651628
references.citation: N Engl J Med. 2001 Jul 26;345(4):256-8
references.pmid: 11474663
references.citation: FEMS Microbiol Lett. 2007 Feb;267(2):207-13
references.pmid: 17166229
references.citation: Gene. 1996 Feb 22;169(1):47-52
references.pmid: 8635748
references.citation: N Engl J Med. 2012 Sep 13;367(11):1035-44
references.pmid: 22970946
references.citation: Vet Rec. 1999 Mar 6;144(10):255-8
references.pmid: 10209817
references.citation: Infect Immun. 2013 Apr;81(4):1121-8
references.pmid: 23340315
references.citation: Emerg Infect Dis. 2005 Sep;11(9):1458-60
references.pmid: 16229782
references.citation: J Bacteriol. 2000 Mar;182(5):1364-73
references.pmid: 10671460
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14246-51
references.pmid: 15377793
references.citation: J Clin Microbiol. 1986 Sep;24(3):330-2
references.pmid: 3489731
references.citation: J Infect Dis. 2002 Oct 15;186(8):1115-21
references.pmid: 12355362
references.citation: Clin Microbiol Rev. 2005 Apr;18(2):383-416
references.pmid: 15831829
references.citation: FEMS Microbiol Lett. 2007 Dec;277(2):115-22
references.pmid: 18031330
references.citation: PLoS One. 2013 Nov 05;8(11):e79461
references.pmid: 24223950
references.citation: Nat Rev Microbiol. 2006 Apr;4(4):272-82
references.pmid: 16541135
references.citation: J Bacteriol. 2005 Nov;187(22):7857-62
references.pmid: 16267310
references.citation: Microbiol Mol Biol Rev. 2004 Dec;68(4):692-744
references.pmid: 15590781
references.citation: Infect Immun. 2007 Sep;75(9):4316-25
references.pmid: 17562762
references.citation: Microb Pathog. 2007 Feb-Mar;42(2-3):98-103
references.pmid: 17261358
references.citation: Nature. 1998 Sep 17;395(6699):213
references.pmid: 9751039
references.citation: Am J Respir Cell Mol Biol. 2000 Jun;22(6):685-92
references.pmid: 10837365
references.citation: J Bacteriol. 2003 Jul;185(13):3735-44
references.pmid: 12813066
references.citation: Infect Immun. 2007 Jun;75(6):2765-75
references.pmid: 17371858
references.citation: Mol Microbiol. 2005 Feb;55(3):687-98
references.pmid: 15660996
references.citation: Infect Immun. 2004 Dec;72(12):6961-8
references.pmid: 15557618
references.citation: J Bacteriol. 1999 Jul;181(13):4026-34
references.pmid: 10383971
references.citation: PLoS One. 2013 Jul 02;8(7):e67881
references.pmid: 23844117
references.citation: Microb Pathog. 1998 May;24(5):269-75
references.pmid: 9600859
references.citation: Infect Immun. 2006 Nov;74(11):6124-34
references.pmid: 16954394
references.citation: Infect Immun. 2007 Apr;75(4):2035-45
references.pmid: 17220316
references.citation: Antimicrob Agents Chemother. 1999 Mar;43(3):465-70
references.pmid: 10049252
references.citation: EMBO J. 2000 Nov 15;19(22):5989-99
references.pmid: 11080146
references.citation: Infect Immun. 1998 Jul;66(7):3113-9
references.pmid: 9632574
references.citation: Infect Immun. 2003 Aug;71(8):4341-50
references.pmid: 12874311
references.citation: Microbiology (Reading). 2001 Jan;147(Pt 1):111-20
references.pmid: 11160805
references.citation: PLoS One. 2012;7(5):e37324
references.pmid: 22624016