Imperial College London
Alternate

Dr Abigail Clements

Faculty of Natural Sciences, Department of Life Sciences

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 7681a.clements

 
 
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Location

 

1.42Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wilksch:2011:10.1371/journal.ppat.1002204,
author = {Wilksch, JJ and Yang, J and Clements, A and Gabbe, JL and Short, KR and Cao, H and Cavaliere, R and James, CE and Whitchurch, CB and Schembri, MA and Chuah, MLC and Liang, Z-X and Wijburg, OL and Jenney, AW and Lithgow, T and Strugnell, RA},
doi = {10.1371/journal.ppat.1002204},
journal = {PLOS Pathogens},
title = {MrkH, a novel c-di-GMP-dependent transcriptional activator, controls Klebsiella pneumoniae biofilm formation by regulating type 3 fimbriae expression},
url = {http://dx.doi.org/10.1371/journal.ppat.1002204},
volume = {7},
year = {2011}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Klebsiella pneumoniae causes significant morbidity and mortality worldwide, particularly amongst hospitalized individuals. The principle mechanism for pathogenesis in hospital environments involves the formation of biofilms, primarily on implanted medical devices. In this study, we constructed a transposon mutant library in a clinical isolate, K. pneumoniae AJ218, to identify the genes and pathways implicated in biofilm formation. Three mutants severely defective in biofilm formation contained insertions within the mrkABCDF genes encoding the main structural subunit and assembly machinery for type 3 fimbriae. Two other mutants carried insertions within the yfiN and mrkJ genes, which encode GGDEF domain- and EAL domain-containing c-di-GMP turnover enzymes, respectively. The remaining two isolates contained insertions that inactivated the mrkH and mrkI genes, which encode for novel proteins with a c-di-GMP-binding PilZ domain and a LuxR-type transcriptional regulator, respectively. Biochemical and functional assays indicated that the effects of these factors on biofilm formation accompany concomitant changes in type 3 fimbriae expression. We mapped the transcriptional start site of mrkA, demonstrated that MrkH directly activates transcription of the mrkA promoter and showed that MrkH binds strongly to the mrkA regulatory region only in the presence of c-di-GMP. Furthermore, a point mutation in the putative c-di-GMP-binding domain of MrkH completely abolished its function as a transcriptional activator. In vivo analysis of the yfiN and mrkJ genes strongly indicated their c-di-GMP-specific function as diguanylate cyclase and phosphodiesterase, respectively. In addition, in vitro assays showed that purified MrkJ protein has strong c-di-GMP phosphodiesterase activity. These results demonstrate for the first time that c-di-GMP can function as an effector to stimulate the activity of a transcriptional activator, and explain how type 3 fimbriae expression is coordinated with
AU  - Wilksch,JJ
AU  - Yang,J
AU  - Clements,A
AU  - Gabbe,JL
AU  - Short,KR
AU  - Cao,H
AU  - Cavaliere,R
AU  - James,CE
AU  - Whitchurch,CB
AU  - Schembri,MA
AU  - Chuah,MLC
AU  - Liang,Z-X
AU  - Wijburg,OL
AU  - Jenney,AW
AU  - Lithgow,T
AU  - Strugnell,RA
DO  - 10.1371/journal.ppat.1002204
PY  - 2011///
SN  - 1553-7366
TI  - MrkH, a novel c-di-GMP-dependent transcriptional activator, controls Klebsiella pneumoniae biofilm formation by regulating type 3 fimbriae expression
T2  - PLOS Pathogens
UR  - http://dx.doi.org/10.1371/journal.ppat.1002204
UR  - http://hdl.handle.net/10044/1/32937
VL  - 7
ER  -
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