In the beginning of the XXI century, tuberculosis still causes three deaths every minute and 8 million people become infected each year. A possible explanation for the successful transmission of this disease relies on the aerial propagation from infected patients. Tuberculosis also affects a variety of mammals including cattle, but disease in humans and animals is caused by different species of the Mycobacterium genus: Mycobacterium tuberculosis and Mycobacterium bovis respectively. However, it is worthy to remember that bacteria responsible for tuberculosis in cattle are rarely transmitted to and between humans.
Inside the NEWTBVAC project research teams from Institut de Pharmacologie et de Biologie Structurale (CNRS/ Université Toulouse III Paul Sabatier) from Toulouse led by Christophe Guilhot, of the Institut Pasteur Paris led by Roland Brosch and the University of Zaragoza and are interested in understanding why bacteria from animal origin are not transmitted to the human population. These scientists have discovered three mutations affecting the virulence regulatory system PhoPR that are exclusively present in animal-adapted strains and some clinical isolates restricted to West Africa. These mutations severely affect the function of PhoPR and consequently M. bovis loss several PhoPR-dependent phenotypes that might impact on transmission of bovine strains to the human host.
This work led the scientists to propose a mechanism to explain the evolution of different Mycobacterium species and its adaptation to different hosts. Also, in understanding disease transmission it will be also possible to design novel intervention strategies that block propagation of mycobacterial diseases.
Significance
In 1901, when Robert Koch proposed that the bacilli causing human and bovine tuberculosis were not identical, this view caused much controversy. Now, 113 y later, we know that the bovine tuberculosis agent, M. bovis, together with other animal strains, forms a separate phylogenetic lineage apart from the human M. tuberculosis lineages, but the molecular reasons why bovine and animal strains only play minor roles in human tuberculosis epidemiology remain unknown. Herein, we show by genetic transfer and virulence experiments that specific mutations in a virulence regulator contribute to lower fitness and virulence of M. bovis and related strains for the human host, likely obstructing the capacity of causing overt disease needed for efficient human to- human transmission.
Read the whole publication in PNAS of 21 July 2014
Source: TBVI