Uddannelses- og Forskningsministeriet - Molecular mechanisms of the Klebsiella CrrA/CrrB two-component system leading to acquisition of colistin resistance

Project: Research

Project Details


Klebsiella pneumoniae is a commensal human pathogen with the
unfortunate ability to develop antibiotic resistance. One of the “last resort”
antibiotics is colistin, which compromises bacterial membrane stability and
transport. This project aims is to study a K. pneumoniae-specific twocomponent
system, CrrA/CrrB, in which a series of mutations has been
observed to yield colistin resistance.
The project will study the molecular effects of the antibiotic-resistance
yielding mutations by mass spectrometric phosphoprotein analysis. We
hypothesise that the mutations affect the efficiency of the signal-transducing
phosphorylations of CrrA/CrrB. This part of the project will also require
method optimization for enrichment of the labile phosphorylations that are
found in two-component systems.
Furthermore, we wish to investigate the function of a key protein, CrrC,
whose expression is induced by (mutated) CrrA/CrrB. The initial
approaches are transcriptomics and proteomics surveys to glean an
overview of the effect of CrrC expression. The surveys will be followed
isolation of direct CrrC interaction partners and genetic verifications.
Effective start/end date01/07/202130/09/2024