Low Dose Aerosol Fitness at the Innate Phase of Murine Infection Better Predicts Virulence amongst Clinical Strains of Mycobacterium tuberculosis
Cáceres, Neus (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Llopis, Isaac (Universitat Politècnica de Catalunya. Escola Superior d'Agricultura de Barcelona)
Marzo, Elena (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Prats, Clara (Universitat Politècnica de Catalunya. Escola Superior d'Agricultura de Barcelona)
Vilaplana, Cristina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
de Viedma, Dario Garcia (Hospital General Universitario Gregorio Marañón)
Samper, Sofía (Hospital Universitario Miguel Servet (Saragossa))
Lopez, Daniel (Universitat Politècnica de Catalunya. Escola Superior d'Agricultura de Barcelona)
Cardona, Pere-Joan (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Universitat Autònoma de Barcelona

Date:	2012
Abstract:	Evaluation of a quick and easy model to determine the intrinsic ability of clinical strains to generate active TB has been set by assuming that this is linked to the fitness of Mycobacterium tuberculosis strain at the innate phase of the infection. Thus, the higher the bacillary load, the greater the possibility of inducting liquefaction, and thus active TB, once the adaptive response is set. The virulence of seven clinical Mycobacterium tuberculosis strains isolated in Spain was tested by determining the bacillary concentration in the spleen and lung of mice at weeks 0, 1 and 2 after intravenous (IV) inoculation of 10 4 CFU, and by determining the growth in vitro until the stationary phase had been reached. Cord distribution automated analysis showed two clear patterns related to the high and low fitness in the lung after IV infection. This pattern was not seen in the in vitro fitness tests, which clearly favored the reference strain (H37Rv). Subsequent determination using a more physiological low-dose aerosol (AER) inoculation with 10 2 CFU showed a third pattern in which the three best values coincided with the highest dissemination capacity according to epidemiological data. The fitness obtained after low dose aerosol administration in the presence of the innate immune response is the most predictive factor for determining the virulence of clinical strains. This gives support to a mechanism of the induction of active TB derived from the dynamic hypothesis of latent tuberculosis infection.
Note:	Altres ajuts: The research leading to these results has received funding from the European Community's 7th Framework Programme HEALTH-2007-2.3.2-2 (FP7/2007-2013: TOPLATENT-TB project under grant agreement 200999). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PloS one, Vol. 7 (january 2012) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0029010
PMID: 22235258

9 p, 674.3 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles