Relationship between pyrazinamide resistance, loss of pyrazinamidase activity, and mutations in the pncA locus in multidrug-resistant clinical isolates of Mycobacterium tuberculosis

M Mestdagh; P A Fonteyne; L Realini; R Rossau; G Jannes; W Mijs; K A De Smet; F Portaels; E Van den Eeckhout

doi:10.1128/AAC.43.9.2317

Relationship between pyrazinamide resistance, loss of pyrazinamidase activity, and mutations in the pncA locus in multidrug-resistant clinical isolates of Mycobacterium tuberculosis

Antimicrob Agents Chemother. 1999 Sep;43(9):2317-9. doi: 10.1128/AAC.43.9.2317.

Authors

M Mestdagh¹, P A Fonteyne, L Realini, R Rossau, G Jannes, W Mijs, K A De Smet, F Portaels, E Van den Eeckhout

Affiliation

¹ Laboratory for Pharmaceutical Biotechnology, FFW, University of Ghent, 9000 Ghent, Belgium.

Abstract

Sixty-two Mycobacterium tuberculosis isolates were tested for pyrazinamidase activity, and their pyrazinamide susceptibility was determined by the radiometric method. Sequencing of pncA genes in the 23 resistant strains revealed mutations in 16 pyrazinamidase-negative strains, 11 of which had not been previously described. Six isolates containing wild-type pncA might possess alternative resistance mechanisms.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amidohydrolases / genetics
Amidohydrolases / metabolism*
Antitubercular Agents / pharmacology*
Drug Resistance, Multiple
Gene Expression Regulation, Enzymologic
Mutation
Mycobacterium tuberculosis / classification
Mycobacterium tuberculosis / drug effects*
Mycobacterium tuberculosis / enzymology*
Mycobacterium tuberculosis / isolation & purification
Pyrazinamide / pharmacology*

Substances

Antitubercular Agents
Pyrazinamide
Amidohydrolases
pyrazinamide deamidase