THE PYRUVATE DEHYDROGENASE E1 SUBUNIT RV2241 (ACEE) OF MYCOBACTERIUM TUBERCULOSIS IS DIFFERENTIALLY EXPRESSED IN LOCAL CLINICAL ISOLATES AND IS IMMUNOGENIC IN PULMONARY TUBERCULOSIS PATIENTS.

PABLO SCHIERLOH; LAURA KLEPP; GARCÍA M; CAMILA VAZQUEZ; ROXANA VALERIA ROCHA; FEDERICO BLANCO; BEATRIZ LÓPEZ; VIVIANA RITACCO; MARÍA DEL CARMEN SASIAIN; FABIANA BIGI

Mar del Plata

Congreso; SAIC-SAI 2014; 2014

SAIC-SAI

Mycobacterium tuberculosis (Mtb), formerly regarded as highly conserved specie, displays a considerable degree of genetic variability that can influence the outcome of the disease as well as the innate and adaptive immune response. By proteomic approaches we searched for proteins that were differentially expressed between two local clinical isolates, one from Latin-American-Mediterranean (LAM) and other from Haarlem (H) lineages. In order to analyze the immunogenic ability of differentially expressed proteins, we cloned and produced recombinant fusion proteins and tested specific antibody and cell mediated immune responses in TB patient samples (n=40). Besides, we applied a battery of immunoinformatic tools in order to contrast our experimental results. We identified seven differentially expressed proteins that were confirmed at transcriptional level. Four of these proteins were successfully cloned: Rv2241, Rv0009, Rv0407 and Rv2624c. We found that all these proteins are able to induce humoral and T-cell mediated IFN-γ (IGRA) responses in patients with drug-sensitive and drug-resistant tuberculosis. However, ROC analysis indicates that only anti-Rv2241 serological response exhibits considerable potential as TB biomarker (Area under ROC≥85%, p