ROLE OF PII PROTEIN ON THE METABOLISM OF M. tuberculosis: MODULATION OF ACYL-COA ACTIVITY

HUERGO L; ENSINCK D; DIACOVICH L; GAGO GABRIELA; GRAMAJO H; EDILEUSA C.M. GERHARDT

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias - LIII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2017

Sociedades de Biociencias - LIII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB)

PII proteins are a family of signal transduction proteins which play a key role in the regulation of nitrogen metabolism. Recently, it has been suggested that the range of metabolic pathways regulated by them may be greater than described in the literature. In Azospirillum brasilense, Escherichia coli and chloroplasts of Arabidopsis thalianaPII proteins are able to interact with the acetyl-CoA carboxylase complex and therefore to inhibit its activity. Those results led to the proposal that PII-BCCP interaction would be conserved throughoutother organisms.This interaction has not been previously studied in actinomicetes.In general, these bacteria codify for several acyl-CoA carboxylases(ACCase) but only one PII protein. Unlike other organisms their ACCases are able to carboxylate other short chain acyl-CoA substrates apart from acetyl-CoA. From the analysis of the M. tuberculosis genome, it can be predicted up to six putative ACCases, some of which are essential for the pathogen. In this works we evaluated the possible interaction between the PII protein and the AccA3 α subunit of an ACCasa complex from M. tuberculosis and analyzed the effect of PII protein in the bacteria physiology. We proved the ability of PII to bind AccA3 by the co-purification of the proteins from a cell extract of M. Smegmatis which overexpresses PII. The ACCase activity, studied by measuring the incorporation of radiolabelled bicarbonate, was modulated in presence of PII. Finally, it has been observed an increase on the M. smegmatis survival after being internalized by macrophages when overexpressing PII. According to these results PII would be also involved in the regulation of carbon metabolism, which could be of relevance in different stages of the infection process.