CLOSTNET PUBLICATIONS

Reconsidering the Sporulation Characteristics of Hypervirulent Clostridium difficile BI/NAP1/027
DA Burns*, D Heeg*, ST Cartman and NP Minton  (joint first authorship)
Clostridia Research Group, School of Molecular Medical Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, United Kingdom

Abstract
Clostridium difficile is the leading cause of antibiotic-associated diarrhoea and a major burden to healthcare services worldwide. In recent years, C. difficile strains belonging to the BI/NAP1/027 type have become highly represented among clinical isolates. These so-called ‘hypervirulent’ strains are associated with outbreaks of increased disease severity, higher relapse rates and an expanded repertoire of antibiotic resistance. Spores, formed during sporulation, play a pivotal role in disease transmission and it has been suggested that BI/NAP1/027 strains are more prolific in terms of sporulation in vitro than ‘non-epidemic’ C. difficile types. Work in our laboratory has since provided credible evidence to the contrary suggesting that the strain-to-strain variation in C. difficile sporulation characteristics is not type-associated. However, the BI/NAP1/027 type is still widely stated to have an increased rate of sporulation. In this study, we analysed the sporulation rates of 53 C. difficile strains, the largest sample size used to-date in such a study, including 28 BI/NAP1/027 isolates. Our data confirm that significant variation exists in the rate at which different C. difficile strains form spores. However, we clearly show that the sporulation rate of the BI/NAP1/027 type was no higher than that of non-BI/NAP1/027 strains. In addition, we observed substantial variation in sporulation characteristics within the BI/NAP1/027 type. This work highlights the danger of assuming that all strains of one type behave similarly without studying adequate sample sizes. Furthermore, we stress the need for more rigorous experimental procedures in order to quantify C. difficile sporulation more accurately in the future.

Online at PLoS One 15 Sept 2011 http://dx.plos.org/10.1371/journal.pone.0024894

Lipoproteins of bacterial pathogens.
Kovacs-Simon A, Titball RW, Michell SL.
SourceRoom 416, School of Biosciences, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter, Devon, United Kingdom EX4 4QD.

Abstract
Bacterial lipoproteins are a set of membrane proteins with many different functions. Due to this broad-ranging functionality, these proteins have a considerable significance in many phenomena, from cellular physiology through cell division and virulence. Here we give a general overview of lipoprotein biogenesis and highlight examples of the roles of lipoproteins in bacterial disease caused by a selection of medically relevant Gram-negative and Gram-positive pathogens: Mycobacterium tuberculosis, Streptococcus pneumoniae, Borrelia burgdorferi, and Neisseria meningitidis. Lipoproteins have been shown to play key roles in adhesion to host cells, modulation of inflammatory processes, and translocation of virulence factors into host cells. As such, a number of lipoproteins have been shown to be potential vaccines. This review provides a summary of some of the reported roles of lipoproteins and of how this knowledge has been exploited in some cases for the generation of novel countermeasures to bacterial diseases.

Infect Immun. 2011 Feb;79(2):548-61. Epub 2010 Oct 25
PMID: 20974828 [PubMed - indexed for MEDLINE] PMCID: PMC3028857[Available on 2011/8/1]

Molecular basis of toxicity of Clostridium perfringens epsilon toxin.
Bokori-Brown M, Savva CG, Fernandes da Costa SP, Naylor CE, Basak AK, Titball RW.
Source Biosciences, College of Life and Environmental Sciences, University of Exeter, UK Department of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck College, London, UK.

Abstract
Clostridium perfringens ε-toxin is produced by toxinotypes B and D strains. The toxin is the aetiological agent of dysentery in newborn lambs but is also associated with enteritis and enterotoxaemia in goats, calves and foals. It is considered to be a potential biowarfare or bioterrorism agent by the US Government Centers for Disease Control and Prevention. The relatively inactive 32.9 kDa prototoxin is converted to active mature toxin by proteolytic cleavage, either by digestive proteases of the host, such as trypsin and chymotrypsin, or by C.perfringens λ-protease. In vivo, the toxin appears to target the brain and kidneys, but relatively few cell lines are susceptible to the toxin, and most work has been carried out using Madin-Darby canine kidney (MDCK) cells. The binding of ε-toxin to MDCK cells and rat synaptosomal membranes is associated with the formation of a stable, high molecular weight complex. The crystal structure of ε-toxin reveals similarity to aerolysin from Aeromonas hydrophila, parasporin-2 from Bacillus thuringiensis and a lectin from Laetiporus sulphureus. Like these toxins, ε-toxin appears to form heptameric pores in target cell membranes. The exquisite specificity of the toxin for specific cell types suggests that it binds to a receptor found only on these cells.

© 2011 The Authors Journal compilation © 2011 FEBS.

FEBS J. 2011 Apr 23. doi: 10.1111/j.1742-4658.2011.08140.x. [Epub ahead of print]
PMID: 21518257 [PubMed - as supplied by publisher]