A novel sensor kinase-response regulator hybrid controls biofilm formation and type VI secretion system activity in Burkholderia cenocepacia

被引:110
作者
Aubert, Daniel F. [1 ]
Flannagan, Ronald S. [1 ]
Valvano, Miguel A. [1 ,2 ]
机构
[1] Univ Western Ontario, Dept Microbiol & Immunol, Infect Dis Res Grp, Siebens Drake Res Inst, London, ON N6A 5C1, Canada
[2] Univ Western Ontario, Dept Med, Infect Dis Res Grp, Siebens Drake Res Inst, London, ON, Canada
关键词
D O I
10.1128/IAI.01338-07
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Burkholderia cenocepacia is an important opportunistic pathogen causing serious chronic infections in patients with cystic fibrosis (CF). Adaptation of B. cenocepacia to the CF airways may play an important role in the persistence of the infection. We have identified a sensor kinase-response regulator (BCAM0379) named AtsR in B. cenocepacia K56-2 that shares 19% amino acid identity with RetS from Pseudomonas aeruginosa.atsR inactivation led to increased biofilm production and a hyperadherent phenotype in both abiotic surfaces and lung epithelial cells. Also, the atsR mutant overexpressed and hypersecreted an Hcp-like protein known to be specifically secreted by the type VI secretion system (T6SS) in other gram-negative bacteria. Amoeba plaque assays demonstrated that the atsR mutant was more resistant to Dictyostelium predation than the wild-type strain and that this phenomenon was T6SS dependent. Macrophage infection assays also demonstrated that the atsR mutant induces the formation of actin-mediated protrusions from macrophages that require a functional Hcp-like protein, suggesting that the T6SS is involved in actin rearrangements. Three B. cenocepacia transposon mutants that were found in a previous study to be impaired for survival in chronic lung infection model were mapped to the T6SS gene cluster, indicating that the T6SS is required for infection in vivo. Together, our data show that AtsR is involved in the regulation of genes required for virulence in B. cenocepacia K56-2, including genes encoding a T6SS.
引用
收藏
页码:1979 / 1991
页数:13
相关论文
共 57 条
[51]   Molecular characterization of a functional type VI secretion system from a clinical isolate of Aeromonas hydrophila [J].
Suarez, Giovanni ;
Sierra, Johanna C. ;
Sha, Jian ;
Wang, Shaofei ;
Erova, Tatiana E. ;
Fadl, Amin A. ;
Foltz, Sheri M. ;
Horneman, Amy J. ;
Chopra, Ashok K. .
MICROBIAL PATHOGENESIS, 2008, 44 (04) :344-361
[52]  
SUSSMAN M, 1987, METHOD CELL BIOL, V28, P9
[53]   Attenuated virulence of a Burkholderia cepacia type III secretion mutant in a murine model of infection [J].
Tomich, M ;
Griffith, A ;
Herfst, CA ;
Burns, JL ;
Mohr, CD .
INFECTION AND IMMUNITY, 2003, 71 (03) :1405-1415
[54]   Multiple sensors control reciprocal expression of Pseudomonas aeruginosa regulatory RNA and virulence genes [J].
Ventre, I ;
Goodman, AL ;
Vallet-Gely, I ;
Vasseur, P ;
Soscia, C ;
Molin, S ;
Bleves, S ;
Lazdunski, A ;
Lory, S ;
Filloux, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (01) :171-176
[55]   Histidine kinases and response regulator proteins in two-component signaling systems [J].
West, AH ;
Stock, AM .
TRENDS IN BIOCHEMICAL SCIENCES, 2001, 26 (06) :369-376
[56]   Vibrio cholerae Hcp, a secreted protein coregulated with HlyA [J].
Williams, SG ;
Varcoe, LT ;
Attridge, SR ;
Manning, PA .
INFECTION AND IMMUNITY, 1996, 64 (01) :283-289
[57]   Dissection of a type VI secretion system in Edwardsiella tarda [J].
Zheng, Jun ;
Leung, Ka Yin .
MOLECULAR MICROBIOLOGY, 2007, 66 (05) :1192-1206