Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: September 10, 2005
Publication Date: October 15, 2005
Citation: Halling, S.M., Jensen, A.E. 2005. Antibiotic sensitivities of Brucella to Macrolides and a Lincosamide: An Investigation of the Usual Suspects - 23S RNA and L4 and L22 [abstract]. 58th Brucellosis Research Conference. p. 89. Technical Abstract: One mechanism whereby bacteria become resistant to macrolide and lincosamide antibiotics is mutation of 23S rRNA or ribosomal proteins. Mutations in 23S rRNA can affect antibiotic binding; however, mutations of either ribosomal protein L4 or L22 can “widen” the peptide exit tunnel so bound antibiotics are unable to block nascent peptide transit through the exit tunnel. When antibiotic sensitivity of the OIE classical Brucella biovars and a dolphin, seal, and porpoise isolate was examined using the E test, vast differences were found to the macrolides erythromycin, clarithromycin, azithromycin, and the lincosamide clindamycin. The 23S dRNA sequences identified three polymorphic sites which split the Brucella into three groups: Brucella abortus biovars; B. suis biovars, except biovar 5, and B. canis; and B. melitensis and all the other Brucella including B. suis biovar 5. The B. melitensis and all other group shared two sites with the B. abortus group and one with B. suis group. Only one of the three polymorphic 23S dRNA sites (2610 E. coli numbering) occurred in the peptidyl transferase center, a locus which is highly conserved among bacteria. However, mutation of nt 2610 only slightly increased antibiotic resistance and did not correlate with differences in the levels antibiotic resistance among Brucella. The genes rplD and rplV, encoding ribosomal proteins L4 and L22, respectively, were sequenced. No differences were found among the putative L4 peptides. The putative L22 peptides had one to three copies of “Glycine-Arginine", greatly affecting their predicted folding and hence the width of the peptide exit tunnel. No simple correlation could be made between loci examined here and the differential resistance of Brucella to macrolides or clindamycin, suggesting that these loci along with efflux activities likely contribute to the differences observed in antibiotic resistance. Dendrograms based on 23S dRNA and L22 polymorphisms are similar to previously reported taxonomic relationships based on data such as genomic physical maps. Key words: Dendrogram, taxonomy, ribosome, ribosomal protein.