OVERPRODUCTION OF MYCOBACTERIAL RIBOSOMAL-PROTEIN S13 INDUCES CATALASE PEROXIDASE-ACTIVITY AND HYPERSENSITIVITY TO ISONIAZID IN MYCOBACTERIUM-SMEGMATIS

A Bacillus Calmette Guerlin (BCG) DNA fragment was identified which co nferred hypersensitivity to isoniazid (INH) upon Mycobacterium smegmat is (Ms) when present on a multicopy plasmid. The gene cluster present on this fragment contains the genes encoding ribosomal proteins L36 (r pmJ), S13 (rpsM), S11 (rpsK) and S4 (rpsD), as well as the gene encodi ng initiation factor-1 (infA), an open reading frame of unknown functi on (ORFX) and a putative promoter region. The rpsM gene, from either B CG or Ms is necessary and sufficient to produce the INH-hypersensitive phenotype in Ms, but the gene cluster has no effect on INH sensitivit y when introduced into BCG on a multicopy plasmid. The presence of rps M on a multicopy plasmid also causes an increase in catalase/peroxidas e (Kat/Prx) activity in Ms. The overproduction of S13 may induce a str ess response, resulting in increased expression of katG (encoding Kat/ Prx) in Ms, thereby causing hypersensitivity to INH.