FROMBCTOBA

Evolution and ecology of Bacillus anthracis: the transition from a soil organism to a mammalian pathogen

Coordinatore	UNIVERSITY OF BATH    more  Organization address address: CLAVERTON DOWN city: BATH postcode: BA2 7AY contact info Titolo: Ms. Nome: Hazel Cognome: Wallis Email: send email Telefono: 441225000000
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	280˙180 €
EC contributo	280˙180 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2010-IEF
Funding Scheme	MC-IEF
Anno di inizio	2011
Periodo (anno-mese-giorno)	2011-09-01   -   2013-08-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITY OF BATH  Organization address address: CLAVERTON DOWN city: BATH postcode: BA2 7AY contact info Titolo: Ms. Nome: Hazel Cognome: Wallis Email: send email Telefono: 441225000000	UK (BATH)	coordinator	280˙180.00

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 Obiettivo del progetto (Objective)

'Despite their importance, little is known about the origins of many emerging human pathogens and the way that invertebrates could shaped their evolution. Bacillus anthracis, the causative agent of anthrax, is closely related to the important insect associated pathogens B. cereus and B. thuringiensis. In B. anthracis, it has been proposed that the horizontal acquisition of the mammalian virulence regulon atxA created a dynamic tension with the insect virulence regulon plcR, which resulted in the functional inactivation of PlcR. The isolate of B. cereus G9241 caused an illness resembling inhalational anthrax and possesses functional versions of atxA and plcR. We hypothesize that this strain represents an early stage isolate recently derived from an insect pathogen in which the competition of the atxA and plcR regulons has yet to resolved. In this proposal we will address the contribution of AtxA and PlcR to gene regulation and virulence in this emerging B. anthracis-like strain. We will develop insect, soil amoeba and mammalian macrophage infection models and use these to compare the B. cereus type strain ATCC14579, B. anthracis Sterne and B. cereus G9241. Furthermore, we will directly address the impact of AtxA upon B. cereus G9241 by means of competition assays with a knockout mutant atxA and monitor reporter gene expression in the mutant and the parent strain in both insect and mammalian tissue culture conditions. Finally, we will conduct micro evolution studies by repeated challenge through the M. sexta host to elucidate the selection pressure acting on the competing AtxA and PlcR regulons in invertebrate infections. A deeper understanding of the molecular biology of B. anthracis virulence could afford novel strategies for future treatments or vaccination against anthrax. Also, the study of B. anthracis with insects and soil amoeba will also provide useful information for the management of anthrax contaminated sites.'

Introduzione (Teaser)

Often diseases emerge due to adaptation of pathogens to new hosts or environments. As a result, greater understanding of their biology, virulence and evolution would be useful for the design of effective treatment strategies.