Interactions between Viomycin Resistance and Streptomycin Resistance on Ribosomes of Mycobacterium smegmatis

Abstract

We have investigated the mechanism of the expression of resistance to high levels of viomycin and coresistance to streptomycin in a mutant strain of Mycobacterium smegmatis ATCC 14468 (AC-13) which was obtained by serial transfers of parental cells to media containing increasing concentrations of viomycin. It was shown previously that resistance to viomycin by strain AC-13 was due to an alteration in the 50 S ribosomal subunit (20). However, genetic analysis has shown that mutation in 50 S subunits alone gave only low level resistance to viomycin. When a streptomycin resistant mutation (caused by an alteration in the 30 S subunit) was introduced into the low level viomycin resistant recombinant strains, most of them were highly resistant to viomycin. Some recombinants were resistant to intermediate levels of viomycin, and the remainder were not affected by the introduction of the strr allele.Studies with in vitro cell-free systems have shown that streptomycin resistant 30 S ribosomal subunits obtained from a high level viomycin resistant recombinant were able to modify the levels of resistance to viomycin expressed by the 50 S ribosomal subunit. These findings provide additional evidence concerning the functional relationship between 30 S and 50 S ribosomal components in ribosomes.

Molecular analysis of kanamycin and viomycin resistance in Mycobacterium smegmatis by use of the conjugation system

“…Strains E, M, A, and O-1 were isolated from ATCC 14468 by Yamada et al by resistance to viomycin, but they showed pleiotropic drugresistant phenotypes (27). The mutational sites for the resistance to kanamycin, viomycin, and streptomycin of these mutants have been characterized as being on the ribosomal subunits (14,15,27). Strains AC21, AC22, and AC23 were isolated by resistance to kanamycin but showed divergent levels of resistance.…”

The translocation inhibitor tuberactinomycin binds to nucleic acids and blocks the in vitro assembly of 50S subunits

“…The altered ribosomes were cross-resistant to streptomycin and kanamycin. These stu-dies suggested that the expression of high level resistance to viomycin can be generated only by a combination of several alterations of the ribosomal constituents (8)(9)(10).…”

Interaction between 30 S Ribosomal Components in a Viomycin Resistant Mutant of Mycobacterium smegmatis

“…Biochemical data suggested that the vicC mutation may not be ribosomal ( Table 4) in spite of the location of vicC close to argB where several of the mycobacterial ribosomal genes are located (2). It seems likely that vicC also determines a ribosomal component, but the level of resistance was too low to be detected in our cell free amino acid incorporation system.…”

“…We have found that resistance to viomycin as a result of changes in the 50 S ribosomal subunit was also influenced by the addition of mutations to 30 S ribosomal genes including str (2). Thus, the mechanism of viomycin resistance is complicated and investigations of the mechanism of viomycin resistance will provide us with information on the structure and function of mycobacterial ribosomes.…”