Sensitivity of elongation factor Tu (EF-Tu) from different bacterial species to the antibiotics efrotomycin, pulvomycin and MDL 62879

Abstract

The sensitivity of elongation factor Tu (EF-Tu) from different species of bacteria to the EF-Tu-binding antibiotics efrotomycin, pulvomycin and MDL 62879 was tested by measuring the effect of these antibiotics on cell-free protein synthesis systems. EF-Tu from four different Gram-negative species was sensitive to all three antibiotics. Among Gram-positive bacteria, EF-Tu of Baciiius subtiiis, Staphylococcus aureus and Enterococcus faecaiis was resistant to efrotomycin and less sensitive to pulvomycin than EF-Tu of Gram-negative bacteria. EF-Tus from streptococci were significantly less sensitive than EF-Tus from Gram-negative bacteria to both efrotomycin and pulvomycin. All of the EF-Tus were sensitive to MDL 62879. The same sensitivity pattern emerged from GDP exchange assays, performed with partially purified EF-Tu from different bacterial species and pure Escherichia coli EF-Ts. These results suggest that the site of action of MDL 62879 is more conserved among bacterial species than those of efrotomycin and pulvomycin. Heterogeneity of EF-Tus from different bacterial species was also reflected in differences in their apparent molecular masses estimated by SDS-PAGE. EF-Tus from the Gram-positive species had higher molecular masses than those from all but one of the Gram-negative species.

Antimicrobial Growth Promoters Used in Animal Feed: Effects of Less Well Known Antibiotics on Gram-Positive Bacteria

“…The product is inactive against gram-negative bacteria because it cannot penetrate the cell, although EF-Tu of gram-negative bacteria is inhibited by efrotomycin in cell-free systems (105). Some activity against Neisseria gonorrhoeae and Haemophilus influenzae has been demonstrated (138). Streptococcal species are relatively insensitive (138).…”

“…Some activity against Neisseria gonorrhoeae and Haemophilus influenzae has been demonstrated (138). Streptococcal species are relatively insensitive (138). Efrotomycin is inactive against staphylococci (105,138), some Lactobacillus species (138), certain enterococcal species (155), and some Bacillus species (138) due to the insensitivity of their EF-Tu to this antibiotic.…”

“…Streptococcal species are relatively insensitive (138). Efrotomycin is inactive against staphylococci (105,138), some Lactobacillus species (138), certain enterococcal species (155), and some Bacillus species (138) due to the insensitivity of their EF-Tu to this antibiotic. The susceptibility patterns of the various enterococcal species seem to be the inverse of those of bambermycin, with the species of the E. faecium group (E. faecium, E. durans, E. hirae, and E. mundtii) being susceptible and the other species being resistant (155).…”

“…Efrotomycin belongs to the kirromycin-like class of antibiotics and is produced by Nocardia lactamdurans. It is an N-methylhydroxypridone glycoside (59,66,138,232). The molecular structure consists of a central dihydrooxytetrahydrofurane ring, a pyridone ring system, and a goldimioc acid (168) Efrotomycin inhibits bacterial growth by the formation of a nondissociable ribosome elongation factor Tu (EF-Tu) complex (137,246).…”

Natural kirromycin resistance of elongation factor Tu from the kirrothricin producer Streptomyces cinnamoneus

“…The resulting SlOO fraction was mixed with NH4C1-washed E. coli ribosomes, prepared as described by Landini et al (1993), and assayed for polyU-directed polyphe synthesis, as described above.…”