Effect of Subinhibitory Concentrations of Antibiotics and Disinfectants on IS<i>Aba</i>-Mediated Inactivation of Lipooligosaccharide Biosynthesis Genes in <i>Acinetobacter baumannii</i>
Inactivation of the lipooligosaccharide (LOS) biosynthesis genes <i>lpxA</i>, <i>lpxC</i> and <i>lpxD</i> by IS<i>Aba</i> insertion elements results in high-level resistance to colistin in <i>A. baumannii</i>. In the present study, we quant...
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| Format: | Book |
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MDPI AG,
2021-10-01T00:00:00Z.
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| Summary: | Inactivation of the lipooligosaccharide (LOS) biosynthesis genes <i>lpxA</i>, <i>lpxC</i> and <i>lpxD</i> by IS<i>Aba</i> insertion elements results in high-level resistance to colistin in <i>A. baumannii</i>. In the present study, we quantify the rate of spontaneous insertional inactivation of LOS biosynthesis genes by IS<i>Aba</i> elements in the ATCC 19606-type strain and two multidrug clinical isolates. Using insertional inactivation of <i>lpxC</i> by IS<i>Aba</i>11 in the ATCC 19606 strain as a model, we determine the effect of several subinhibitory concentrations of the antibiotics, namely tetracycline, ciprofloxacin, meropenem, kanamycin and rifampicin, as well as the disinfectants ethanol and chlorhexidine on IS<i>Aba</i>11 insertion frequencies. Notably, subinhibitory concentrations of tetracycline significantly increased IS<i>Aba</i>11 insertion, and rifampicin completely inhibited the emergence of colistin resistance due to IS<i>Aba</i>11 inactivation of <i>lpxC</i>. Sequencing of IS<i>Aba</i>11 insertion sites within the <i>lpxC</i> gene demonstrated that insertions clustered between nucleotides 382 and 618 (58.3% of unique insertions detected), indicating that this may be a hotspot for IS<i>Aba</i>11 insertion. The alignment of insertion sites revealed a semi-conserved AT-rich consensus sequence upstream of the IS<i>Aba</i>11 insertion site, suggesting that IS<i>Aba</i>11 insertion sites may be sequence-dependent. This study explores previously uncharacterized aspects regarding the acquisition of colistin resistance through insertional activation in LOS biosynthesis genes in <i>A. baumannii</i>. |
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| Item Description: | 10.3390/antibiotics10101259 2079-6382 |