Membrane biology

Event Date: 
Wednesday, March 27, 2013 - 18:00 - 18:15
Institution: 
University of Sydney
Title: 

Insight into the specificity of Wzx for O-antigen processing

Abstract: 

Most Gram-negative bacteria have an O antigen that consists of repeats of 3-6 sugars, and serve as an essential factor for host colonization in many disease-causing bacteria. Until now, most known O antigens are assembled by the Wzx/Wzy pathway. This involves the assembly of repeat units within the cytoplasmic face of inner membrane on a lipid carrier, undecaprenol-phosphate, which are translocated across membrane by the Wzx translocases. In the periplasmic face, the repeat units are polymerized by the Wzy polymerase, and then subsequently ligated to preformed lipid A-core in the periplasm. Earlier works have shown Wzx translocases have a relax specificity requirement over the repeat-unit structures. However, this could neither correlate to the presence of O antigen with defined structures in each respective bacteria, nor could it explain the biological diversity of Wzx translocases. Our data show that Wzx translocases have a serotype specificity over their native repeat-unit structures, and provides evidence that the earlier conclusion were obscured by protein overexpression. This provides relevant explanation to the presence of highly diverse, yet structurally defined bacterial surface polysaccharides in nature.

Event Date: 
Wednesday, September 26, 2012 - 18:15
Institution: 
Macquarie University
Title: 

Defining the effluxome of Acinetobacter baumannii

Abstract: 

 
Acinetobacter baumannii is a Gram-negative opportunistic human pathogen known to cause a range of infections in hospitals. Despite their recent emergence, strains of A. baumannii, resistant to essentially all routinely used antibiotics, have been isolated from clinical settings. Bioinformatic analysis identified more than 50 transporter systems with a putative role in drug efflux in the genome of A. baumannii ATCC17978, representing ~2% of all its protein coding ORFs. Based on an assumption that drug transport is often associated with over-expression of a relevant efflux system in the presence of the substrate, high-throughput quantitative reverse-transcriptase PCR (qRT-PCR) has been performed after shock treatments with sub-inhibitory concentrations of antibiotics and differential expression of genes was assessed. This strategy has led to the discovery of novel drug efflux systems and defined physiological functions for previously characterised and novel pumps in drug resistance.
Efflux systems have evolved for millions of years before bacteria such as A. baumannii entered the hospital environment. Presumably, they have initially developed as mechanisms of resistance against naturally occurring substrates. To further characterize the role of efflux systems, cultures of A. baumannii were treated with bioactive natural compounds found in the environment, i.e. soil. These treatments resulted in significant changes in the transcription of efflux pumps indicating their possible role in the defence against compounds found in nature.
Increased expression of efflux systems was also observed when cells of A. baumannii were grown in biofilms compared to planktonic cultures which could suggest that efflux pumps may also play an important role in the functioning of these bacterial communities.

 

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