The HicA toxin from Burkholderia pseudomallei has a role in persister cell formation
Butt, Aaron T.; Higman, VA; Williams, C; et al.Crump, MP; Hemsley, CM; Harmer, Nicholas; Titball, Richard W.
Date: 15 April 2014
Journal
Biochemical Journal
Publisher
Portland Press
Publisher DOI
Related links
Abstract
TA (toxin-antitoxin) systems are widely distributed amongst bacteria and are associated with the formation of antibiotic tolerant (persister) cells that may have involvement in chronic and recurrent disease. We show that overexpression of the Burkholderia pseudomallei HicA toxin causes growth arrest and increases the number of persister ...
TA (toxin-antitoxin) systems are widely distributed amongst bacteria and are associated with the formation of antibiotic tolerant (persister) cells that may have involvement in chronic and recurrent disease. We show that overexpression of the Burkholderia pseudomallei HicA toxin causes growth arrest and increases the number of persister cells tolerant to ciprofloxacin or ceftazidime. Furthermore, our data show that persistence towards ciprofloxacin or ceftazidime can be differentially modulated depending on the level of induction of HicA expression. Deleting the hicAB locus from B. pseudomallei K96243 significantly reduced persister cell frequencies following exposure to ciprofloxacin, but not ceftazidime. The structure of HicA(H24A) was solved by NMR and forms a dsRBD-like (dsRNA-binding domain-like) fold, composed of a triple-stranded β-sheet, with two helices packed against one face. The surface of the protein is highly positively charged indicative of an RNA-binding protein and His24 and Gly22 were functionality important residues. This is the first study demonstrating a role for the HicAB system in bacterial persistence and the first structure of a HicA protein that has been experimentally characterized.
Biosciences - old structure
Collections of Former Colleges
Item views 0
Full item downloads 0
Related items
Showing items related by title, author, creator and subject.
-
Differential effects and interactions of endogenous and horizontally acquired H-NS-like proteins in pathogenic Escherichia coli
Müller, CM; Schneider, G; Dobrindt, U; et al. (Wiley, 4 December 2009)The nucleoid-associated protein H-NS is important for gene regulation in Escherichia coli. We have studied H-NS interaction with StpA and an uncharacterized H-NS-like protein, Hfp, in the uropathogenic E. coli isolate 536 ... -
Photorhabdus adhesion modification protein (Pam) binds extracellular polysaccharide and alters bacterial attachment.
Jones, RT; Sanchez-Contreras, M; Vlisidou, I; et al. (BioMed Central, 12 May 2010)BACKGROUND: Photorhabdus are Gram-negative nematode-symbiotic and insect-pathogenic bacteria. The species Photorhabdus asymbiotica is able to infect humans as well as insects. We investigated the secreted proteome of a ... -
A Burkholderia pseudomallei macrophage infectivity potentiator-like protein has rapamycin-inhibitable peptidylprolyl isomerase activity and pleiotropic effects on virulence
Norville, IH; Harmer, Nicholas; Harding, SV; et al. (American Society for Microbiology, 1 November 2011)Macrophage infectivity potentiators (Mips) are a group of virulence factors encoded by pathogenic bacteria such as Legionella, Chlamydia, and Neisseria species. Mips are part of the FK506-binding protein (FKBP) family, ...