Whole-genome sequence analysis reveals evolution of antimicrobial resistance in a Ugandan colistin resistant Acinetobacter baumannii

Abstract

AbstractIn recent times, pan-drug resistant Acinetobacter baumannii have emerged and continue to spread among critically ill patients, this poses an urgent risk to global and local human health. This study sought to provide the first genomic analysis of a pan-drug resistant Acinetobacter baumannii from Uganda and Africa, and to tell a story of mobile genetic element-mediated antibiotic resistance evolution in the isolate. It was an in-silico study in which intrinsic and acquired antibiotic resistance genes, and/or chromosomal resistance mutations were identified using PATRIC, CARD, NDARO and ResFinder. Screening for insertion sequences was done using ISfinder. Also, plasmid screening, phylogenetic analysis and sequence typing were performed using PlasmidFinder, PATRIC and Gubbin, and MLST respectively.The isolate belonged to the Sequence type 136, belonging to Clonal complex 208 and Global complex 2. This isolate shared close homology with strains from Tanzania. Resistance in the isolate was chromosomally and mobile genetic element-mediated by Acinetobacter-derived cephalosporinases and carbapenem hydrolyzing class D β-lactamses, blaOXA-2, 51, 5 88, 317, blaADC-2, 25. Colistin resistance was associated with previously documented mutants, lpxA and lpxC. Other key resistance genes identified were: aph(3”)-lb, aph(6)-ld, aph(3’)-la, aac(3)-lld, aac(3)-lla, aph(3’)-l, aph(3”)-l, aph(6)-lc, aph(6)-ld, aac(3)-II, III, IV, VI, VIII, IX, X, macA, macB, tetA, tetB, tetR, dfrA, and those of the floR family. RSF1010 like IncQ broad-host-range plasmids and features of pACICU1, pACICU2, and p3ABAYE Acinetobacter baumannii plasmids namely partitioning proteins ParA and B were present. Insertion sequences present included IS3, IS5, IS66 and those of the ISLre2 families.The study described for the first time a pan-drug resistant Acinetobacter baumannii from Uganda, and told a story of mobile genetic element-mediated antibiotic resistance evolution in the isolate despite being limited by pan-drug resistance phenotypic data. It provides a basis to track trends in antibiotic resistance and identification of emerging resistance patterns in Acinetobacter baumannii in Uganda.