Real-time sequencing to decipher the molecular mechanism of resistance of a clinical pan-drug-resistant Acinetobacter baumannii isolate from Marseille, France

Abstract

We compare the whole-genome sequences of two multidrug-resistant clinical Acinetobacter baumannii isolates recovered in the same patient before (ABIsac_ColiS susceptible to colistin and rifampin only) and after (ABIsac_ColiR resistant to colistin and rifampin) treatment with colistin and rifampin. We decipher all the molecular mechanisms of antibiotic resistance, and we found mutations in the rpoB gene and in the PmrAB two-component system explaining resistance to rifampin and colistin in ABIsac_ColiR, respectively.

Fig 1

Mauve alignment of A. baumannii ABIsac_ColiS and ABIsac_ColiR genomes.

Fig 2

Circular representation of A. baumannii ABIsac_ColiR and ABIsac_ColiS chromosomes and antibiotic resistance determinants. The transposon AbaR4 island and class 1 integron were identical in the chromosomes of both strains, whereas pmrA, pmrB, and rpoB mutations were found only in the ABIsac_ColiR chromosome. The genes and the proteins they encode follow: comM, competence protein ComM disrupted/Mg²⁺ chelatase-like protein; tnpA, transposase protein A; tnpB, transposase protein B; tniC, transposition helper protein C; tniD, probable transposition protein; ORF_6, hypothetical protein; ORF_7, hypothetical protein; uspA, universal stress protein; suldelta, sul1delta fusion protein/sulfate permease interrupted by Tn2006; Ab_IS4, IS4 family transposase ORF 1; yeeA, DNA methylase; ORF_12, hypothetical protein; bla_OXA-23, OXA-23 carbapenemase; Ab_IS4, IS4 family transposase ORF 1; suldelta, sul1delta fusion protein/sulfate permease, interrupted by Tn2006; ORF_15, hypothetical protein; comM, competence protein ComM disrupted/Mg²⁺ chelatase-like protein; araC, transcriptional regulator of the AraC family; tnpR, transposon Tn21 resolvase; intI1, IntI1 integrase; aadB, aminoglycoside-2′-adenylyltransferase; aadA2, aminoglycoside adenyltransferase A2; emrE, ethidium bromide-methyl viologen resistance protein EmrE; sul1, dihydropteroate synthase; GCN-5, GCN5-like N-acetyltransferase; tniB, nucleoside triphosphate (NTP)-binding protein; istB, transposon NTP-binding protein; istA, transposase IstA protein; pcaR, regulon regulatory protein; ORF-1373, 4-hydroxybenzoate 3-monooxygenase.