Novel sequence type of carbapenem-resistant Acinetobacter pittii ST1451 with enhanced virulence isolated from septicaemic neonates in India

Abstract

Abstract Background The clinical relevance of Acinetobacter pittii is increasing, but reports of this organism causing neonatal sepsis are rare. Objectives To understand the mechanisms of resistance and virulence of A. pittii isolated from neonatal blood belonging to a novel sequence type. Materials and methods Antibiotic susceptibility, MLST, WGS, phylogenomic comparison with a global collection of carbapenemase-harbouring A. pittii were done. To study the pathogenic potential of novel A. pittii, in vitro and in vivo assays were carried out. Results and discussion Two novel multidrug-resistant A. pittii from neonatal blood belonging to a novel sequence type 1451 (ST1451) were isolated. WGS revealed that the isolates were almost similar (147 SNP distant) and harbouring two carbapenem resistance genes blaNDM-1 with upstream ISAba125 and downstream bleMBL along with blaOXA-58 with upstream ISAba3. Other resistance genes included blaADC-25, blaOXA-533, aph(3″)-Ib, aph(3′)-VIa, aph(6)-Id, aac(3)-IId, mph(E), msr(E), sul2 and tet(39), different efflux pump genes and amino acid substitutions within GyrA (Ser81Leu) and ParC (Ser84Leu; Glu88Ala) were detected among the isolates. The study genomes were closely related to four strains belonging to ST119. The isolates showed biofilm production, serum resistance, growth under iron limiting condition, surface-associated motility and adherence to host cell. Isolates induced cytokine production in the host cell and showed mice mortality. Discussion and conclusions This study is the first report of the presence of blaNDM-1 in A. pittii from India along with another carbapenemase blaOXA-58. Emergence of highly virulent, multidrug-resistant A. pittii with attributes similar to A. baumannii calls for surveillance to identify the novel strains and their pathogenic and resistance potential.