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Ribosomal resistance in the gentamicin producer organism Micromonospora purpurea
Abstract:
The mechanism of resistance of the gentamicin-producing organism Micromonospora purpurea was analyzed. Determination of minimal inhibitory concentrations revealed high resistance to the 4,6-substituted deoxystreptamine aminoglycosides amikacin, gentamicin, kanamycin, netilmicin, sisomicin, and tobramycin and also to lividomycin A and hygromycin B, but susceptibility to streptomycin, dihydrostreptomycin, paromomycin, and neomycin during all phases of the growth cycle. The nonproducing, closely related Micromonospora melanosporea was susceptible to these compounds. In agreement with results from previous studies (R. Benveniste and J. Davies, Proc. Natl. Acad. Sci. U.S.A. 70:2276-2280, 1973), extracts from M. purpurea showed no activity of enzymes specifically modifying gentamicin. 70S ribosomes from M. purpurea but not from M. melanosporea were resistant to inhibition by gentamicin, kanamycin, tobramycin, and lividomycin in a polyuridylic acid-dependent polyphenylalanine synthesis system and susceptible to those compounds which were inhibitory in vivo. The former antibiotics were also unable to induce misreading. Subunit exchange experiments between M. purpurea and M. melanosporea showed that the main site for inhibition and induction of misreading is the 30S subunit (up to gentamicin concentrations of 10 micrograms/ml).
Insights
Micromonospora purpurea exhibits resistance to several aminoglycoside antibiotics due to its 30S ribosomal subunit. This resistance mechanism in gentamicin-producing bacteria is crucial for understanding antibiotic efficacy.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Micromonospora purpurea produces gentamicin, an important aminoglycoside antibiotic.
- Understanding antibiotic resistance mechanisms is critical in clinical and research settings.
Purpose of the Study:
- To elucidate the mechanism of aminoglycoside antibiotic resistance in Micromonospora purpurea.
- To compare resistance profiles between gentamicin-producing and non-producing Micromonospora species.
Main Methods:
- Determination of minimal inhibitory concentrations (MICs) for various aminoglycosides.
- Analysis of gentamicin-modifying enzyme activity in M. purpurea extracts.
- Testing the susceptibility of 70S ribosomes from M. purpurea and M. melanosporea to antibiotics.
- Conducting subunit exchange experiments between 30S and 50S ribosomal subunits.
Main Results:
- M. purpurea showed high resistance to several 4,6-substituted deoxystreptamine aminoglycosides, including gentamicin, amikacin, and tobramycin.
- Susceptibility was observed for streptomycin, paromomycin, and neomycin.
- Ribosomes from M. purpurea, specifically the 30S subunit, were resistant to gentamicin and related compounds, unlike those from M. melanosporea.
- Antibiotics did not induce misreading in the M. purpurea ribosomal system.
Conclusions:
- The primary mechanism of resistance in M. purpurea involves the 30S ribosomal subunit, conferring resistance to specific aminoglycosides.
- The absence of gentamicin-modifying enzymes suggests a ribosomal target-based resistance.
- This ribosomal resistance is specific to gentamicin-producing strains and does not affect susceptibility to all aminoglycosides.