Identification of putative biomarkers for the serodiagnosis of drug-resistant Mycobacterium tuberculosis

Serum from patients infected with drug-resistant or drug-susceptible M. tuberculosis strains and healthy controls was subjected to two-dimensional gel electrophoresis using a western blot approach. This procedure identified nine immunoreactive proteins, which were subjected to MALDI-TOF-MS analysis. Six recombinant proteins, namely rRv2031c, rRv0444c, rRv2145c, rRv3692, rRv0859c, and rRv3040, were expressed and used to determine the immuno-reactivity of 100 serum samples. Antibody reactivity against rRv2031c, rRv3692, and rRv0444c was consistently observed. Among them, the best sensitivity and specificity of rRv3692 were 37% and 95% respectively. Furthermore, when rRv2031c and rRv3692 or rRv2031c, rRv3692, and rRv0444c were combined in 2:1 or equal amounts, the assay sensitivity and specificity were improved to 56.7% and 100% respectively.These results suggest that Rv2031c, Rv3692, and Rv0444c are possible candidate biomarkers for effective use in the serodiagnosis of drug-resistant tuberculosis infections, and a combined formula of these antigens should be considered when designing a subunit assay kit.More than one-third of the world's population is infected with tubercle bacilli. Poor adherence to tuberculosis (TB) control programs, the subsequent emergence of drug-resistant strains and the widespread prevalence of HIV have contributed to the resurgence of this disease [1]. Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis present serious threats to global TB control efforts. The World Health Organization estimated that the number of new MDR-TB cases in 2004 was 425, 000, and 60% of these cases were located in China, India, and the Russian Federation [2,3].Most TB-associated deaths are preventable with early diagnosis and treatment [4], and it has been suggested that a quick and accurate tool for early TB diagnosis could save up to 625, 000 lives each year [5]. Currently, optimal diagnostics for TB are a demanding task and new p