Klebsiella pneumoniae is a neglected bacterial pathogen of importance to elderly, hospitalised patients in e.g. ICUs where it causes pneumonia, wound and urinary tract infections. It is also the commonest cause of sepsis in infants in the developing world. The bacterium is heavily encapsulated, appears to reside extracellularly and grows rapidly in the blood. The genome of this bacterium is relatively large and contains many functionally undefined genes. The studies we are undertaking are aimed at elucidating the processes leading to infection, disease and immunity in small animal models. These studies are directed at defining the role(s) of lipopolysaccharide, iron, conserved membrane proteins and the variable carbohydrate antigens produced by this bacterium in the pathogenesis of K. pneumoniae disease.
Recent research highlights:
- Transcriptional activation of the mrkA promoter of the Klebsiella pneumoniae type 3 fimbrial operon by the c-di-GMP-dependent MrkH protein.
Yang J, Wilksch JJ, Tan JWH, Hocking DM, Webb CT, Lithgow T, Robins-Browne RM, Strugnell RA.
PLoS One 2013; 8(11):e79038.
This study investigated the molecular mechanism for how MrkH functions as a powerful transcriptional activator of the mrk operon (for type 3 fimbriae production). We revealed that MrkH binds to a 12-bp sequence (called the MrkH box) immediately upstream of the mrkA promoter. MrkH activation of mrkA transcription was shown to involve direct interaction of an N-terminal region of MrkH with specific residues of the RNA polymerase α subunit.
- MrkH, a Novel c-di-GMP-Dependent Transcriptional Activator, Controls Klebsiella pneumoniae Biofilm Formation by Regulating Type 3 Fimbriae Expression.
Wilksch JJ, Yang J, Clements A, Gabbe JL, Short KR, Cao H, Cavaliere R, James CE, Whitchurch CB, Schembri MA, Chuah ML, Liang ZX, Wijburg OL, Jenney AW, Lithgow T, Strugnell RA.
PLoS Pathogens 2011; 7(8): e1002204.
Bacterial biofilm formation is a major cause of hospital-acquired infections. This study identified and characterised MrkH - a transcriptional activator of the operon that encodes type 3 fimbriae in Klebsiella pneumoniae and an important regulator for biofilm formation. The activity of MrkH was shown to be regulated by the presence of c-di-GMP – a ubiquitous prokaryotic secondary messenger.
- Nanomechanics measurements of live bacteria reveal a mechanism for bacterial cell protection: the polysaccharide capsule in Klebsiella is a responsive polymer hydrogel that adapts to osmotic stress.
Wang H, Wilksch JJ, Lithgow T, Strugnell RA, Gee ML.
Soft Matter 2013; 9: 7560-67.
Atomic force microscopy (AFM) was used to measure the biophysical behaviour of individual Klebsiella pneumoniae cells in situ. A mechanical model was developed to show that the organization and hydration of the capsule alter in response to the osmotic environment, however there is no change in cytoplasmic turgor pressure. The capsule-deficient mutants however, experience extreme change in turgor pressure under altered osmotic conditions. Our results provide new insight on the biophysical behavior of the bacterial capsule, demonstrating that it is a polymer hydrogel that acts as an ion sponge to dampen the impact of osmotic stress.
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