Abstract
Enzymatic modification is a prevalent mechanism by which bacteria defeat the action of antibiotics. Aminoglycosides are often inactivated by aminoglycoside modifying enzymes encoded by genes present in the chromosome, plasmids, and other genetic elements. The AAC(6′)-Ib (aminoglycoside 6′-N-acetyltransferase type Ib) is an enzyme of clinical importance found in a wide variety of gram-negative pathogens. The AAC(6′)-Ib enzyme is of interest not only because of his ubiquity but also because of other characteristics, it presents significant microheterogeneity at the N-termini and the aac(6′)-Ib gene is often present in integrons, transposons, plasmids, genomic islands, and other genetic structures. Excluding the highly heterogeneous N-termini, there are 45 non-identical AAC(6′)-Ib related entries in the NCBI database, 32 of which have identical name in spite of not having identical amino acid sequence. While some variants conserved similar properties, others show dramatic differences in specificity, including the case of AAC(6′)-Ib-cr that mediates acetylation of ciprofloxacin representing a rare case where a resistance enzyme acquires the ability to utilize an antibiotic of a different class as substrate. Efforts to utilize antisense technologies to turn off expression of the gene or to identify enzymatic inhibitors to induce phenotypic conversion to susceptibility are under way.
Highlights
Enzymatic modification is a prevalent mechanism by which bacteria defeat the action of antibiotics
The action of aminoglycosides is characterized by interactions between the antibiotic molecule and the 16S rRNA
For all aminoglycosides the effect of this interaction is a change of conformation of the decoding A site producing one that resembles the closed state induced by interaction between cognate tRNA and mRNA, it must be noted that not all aminoglycosides seem to bind the same sites of the 16S rRNA
Summary
ADC80806 aac(6 )-Ib pRYC103T24::class 1 integron In4-like, pKSP212::class 1 integron. ADC80825 aac(6 )-Ib aac(6 )-Ib p1658/97::class 1 integron, class 1 integron (Chromosome), class 1 integron, plasmid In238a pRYC103T24::class 1 integron. YP_002286969, ZP_16459764 (genomic scaffold), ZP_19016755 (contig), ACI63027, EGB78408 (contig), EKV58524 (contig). YP_005525242, YP_006289231, YP_006848983, ZP_11603605 (contig), ZP_16142456 (contig), ZP_16146111 (contig), EGK45756 (seq0044), AEP05746, AFI94936, EKE64317 (contig), EKE64588 (contig), AFU38752. Aac(6 )-Ib aac(6 )-Ib aac(6 )-Ib aac(6 )-Ib aac(6 )-Ib9 aac(6 )-Ib-cr aac(6 )-Ib-cr aac(6 )-Ib-cr aac(6 )-Ib-cr aac(6 )-Ib-cr aac(6 )-Ib. Genetic localization pEC-IMP::class 1 integron, pEC-IMPQ::class 1 integron, pb1004::class 1 integron, class 1 integron Class 1 integron Class 1 integron pKPI-6::class 1 integron Class 1 integron Class 1 integron pEK516, pEK499, pEC_L8, pUUH239.2. PHS1387::class 1 integron Class 1 integron pC15-1a, pKP96::class 1 integron, pNDM-MAR, pGUE-NDM, pKDO1, pHe96, pKas, pECZ6-1::class 1 integron, Class 1 integron, pLC108::class 1 integron, pJIE101, pKOX_R1::class 1 integron, class 1 integorn, Species En. cloacae, Salmonella enterica subsp.
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