Expression of ppsD, a gene involved in synthesis of Mycobacterium tuberculosis virulence factor PDIM, reflects treatment response in pulmonary tuberculosis patients

Abstract

Drug resistant tuberculosis (TB) cases are primarily driven by transmission, however, treatment failure and acquisition of drug resistance are still significant issues in drug sensitive TB cases. Study of gene expression in Mycobacterium tuberculosis (Mtb) isolated from poor outcome patients may offer clues towards prediction of treatment response. In the current study, expression of five non-drug target genes (ppsD, embC, Rv1457c, Rv1687c and recB) previously identified to be associated with drug resistance was studied in clinical isolates from patients with different treatment outcomes to examine its correlation to treatment response and acquisition of drug resistance in Mtb. Our results show that expression of ppsD, a gene involved in synthesis of cell wall lipid PDIM, was significantly increased in patients who developed drug resistance during treatment and patients who were drug resistant at diagnosis. On the other hand in longitudinal isolates collected during treatment, ppsD expression decreased consistently in patients who responded to treatment and became culture negative, while it increased in patients who did not respond to treatment as indicated by their culture positive status towards the end of treatment. These results demonstrate that ppsD expression reflects treatment response in TB patients and hence can be potentially used as a marker for predicting treatment response. Additional longitudinal studies with a larger cohort of patients are required to establish application of ppsD expression as a marker of treatment response.