Journal of Microbial & Biochemical Technology

Expired nitric oxide and sputum mycobacterial lipid bodies indicate that pulmonary NO is a double edged sword in tuberculosis

3^rd World Congress and Expo on Applied Microbiology

November 07-09, 2016 Dubai, UAE

Baye Gelaw, Natalie J Garton, Gashaw Mesele, Tadya Abeje, Salie Aylew, Pranabashis Haldar, Abraham Assefa and Michael R Barer

University of Gondar, Ethiopia
University of Leicester, UK
Armauer Hansen Research Institute, Ethiopia

Posters & Accepted Abstracts: J Microb Biochem Technol

Abstract:

Background & Aim: The variable occurrence of lipid body rich (fat) and poorly replicating (lazy) Mycobacterium tuberculosis bacilli in sputum necessitates an explanation of the environmental signals responsible for these phenotypes. Lipid body rich and poorly replicating Mycobacterium tuberculosis bacilli occur at different frequencies in sputum. In vitro, NO stimulates lipid body (LB) accumulation in M. tuberculosis via the dormancy-associated regulon [DosR (DevR)]. We hypothesized that the percentage of lipid body-positive acid fast bacilli (%LB+AFB) in sputum correlates with fractional expired NO (FeNO) and that greater LB responses to NO might be associated with poorer responses to chemotherapy. Methods: In Gondar, Ethiopia, 73 patients with smear positive tuberculosis were recruited and assessed for sputum %LB+AFB, FeNO and HIV status. Weight gain was determined at 7 months in 9 patients as a measure of treatment response. Results: %LB+AFB in patientsâ?? sputum significantly associated with Log10 FeNO concentration (p<0.001) with a linear relationship (r2=0.209, p<0.001). Weight gain showed a negative linear association with %LB+AFB at both 2 (r2=0.196) and 7 months (r2=0.445) of treatment. Stronger correlations of Log10 FeNO concentration with %LB+AFB were apparent after stratification for HIV status with a shallower negative gradient for HIV positives.\ Conclusions: M. tuberculosis LB frequencies in sputum are significantly associated with patient FeNO levels in a manner consistent with bacterial DosR activation by NO in the lung. DosR activation is associated with antibiotic tolerance and may compromise treatment response while bactericidal effects of NO should be beneficial. We suggest that NO is a double-edged sword enabling mycobacterial clearance at high levels but provoking antibiotic tolerance when sub-lethal.

Biography :

Email: tedybayegelaw@gmail.com