Understanding Communication Signals during Mycobacterial Latency through Predicted Genome-Wide Protein Interactions and Boolean Modeling

About 90% of the people infected with Mycobacterium tuberculosis carry latent bacteria that are believed to get activated upon immune suppression. One of the fundamental challenges in the control of tuberculosis is therefore to understand molecular mechanisms involved in the onset of latency and/or reactivation. We have attempted to address this problem at the systems level by a combination of predicted functional protein∶protein interactions, integration of functional interactions with large scale gene expression studies, predicted transcription regulatory network and finally simulations with a Boolean model of the network. Initially a prediction for genome-wide protein functional linkages was obtained based on genome-context methods using a Support Vector Machine. This set of protein functional linkages along with gene expression data of the available models of latency was employed to identify proteins involved in mediating switch signals during dormancy. We show that genes that are up and down regulated during dormancy are not only coordinately regulated under dormancy-like conditions but also under a variety of other experimental conditions. Their synchronized regulation indicates that they form a tightly regulated gene cluster and might form a latency-regulon. Conservation of these genes across bacterial species suggests a unique evolutionary history that might be associated with M. tuberculosis dormancy. Finally, simulations with a Boolean model based on the regulatory network with logical relationships derived from gene expression data reveals a bistable switch suggesting alternating latent and actively growing states. Our analysis based on the interaction network therefore reveals a potential model of M. tuberculosis latency

Integral Prospection of Andean Microbial Ecosystem Project

When microbial ecosystems first started to be reported 10 years ago, nobody reallyhad a notion of the relevance they would have in the Central Andean region.Consequently, the heritage of the microbialites reported in El Peinado, LagunaNegra, Laguna Pozo Bravo, Laguna La Brava, etc. promises to position the Andes asreservoirs of the most relevant modern microbialites on the planet (Table 17.1,Fig. 17.1). Furthermore, the number of different ecosystems is worth paying closeattention to, as it gives rise to questions such as: What favors the development ofthese ecosystems? What are the conditions that influence the precipitation of a carbonaceousor a gypsum system at such a short distance and under similar environmentalconditions, such as at the Atacama salt flat? Why are oncolites distributed so? Untilnow, it has been possible only to survey the systems and to carry out more in-depthstudies in some of them to try to achieve their preservation. Throughout the prospection of the Andean microbial ecosystems (AMEs), some shared characteristics have beenfound from the geological, physical, and chemical points of view [(1) active volcanicincidence: all of the microbial ecosystems that have been found are in some way connectedto areas where active volcanoes are present; (2) underground water input;(3) mixed zones with different salinities: underground low-conductivitywater andsalar thalassic water; (4) two kinds of microbialites found: oncolites (at LagunaNegra, Tres Quebradas, Las Quinoas, etc.) or domes with thrombolites at the bottomand stromatolites at the top surface (at La Brava, Pozo Bravo, Ojos Bravos, and ElPeinado)] and from the biological point of view [(5) predominance of diatoms, themain component in all studied systems; (6) predominance of anaerobic over aerobicphotosynthetic microorganisms; (7) microbial rhodopsin as the main system for producing adenosine triphosphate (ATP); (8) arsenicresistance and bioenergetic mechanisms;and (9) predominance of Carbon fixation pathways other than the Calvincycle]. The biological aspects of these are being studied thoroughly in our lab and arebriefly discussed below.Fil: Farias, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; ArgentinaFil: Villafañe, Patricio Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; ArgentinaFil: Lencina, Agustina Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Catamarca. Universidad Nacional de Catamarca. Centro de Investigaciones y Transferencia de Catamarca; Argentin