First report of New Delhi metallo-β-lactamase-6 (blaNDM-6) gene in Africa identified in a carbapenem-resistant Acinetobacter baumannii clinical isolate

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Background Carbapenem-resistant Acinetobacter baumannii (CRAB) is recognized by the WHO as a critical-priority pathogen reflecting the urgent need for new treatments and interventions due to its extensive antimicrobial resistance and association with high mortality, particularly in healthcare settings. A key resistance mechanism is the production of New Delhi metallo-β-lactamase (NDM) enzymes, which confer resistance to nearly all β-lactam antibiotics, with mortality rates reported to exceed 40% in some studies. Since the first description of bla NDM-1 in 2008, several other variants have emerged. This includes bla NDM-6 , which exhibits enhanced zinc-binding affinity and enzymatic stability with a potential to circumvent emerging metallo-β-lactamase inhibitors. Although bla NDM-6 has been reported in various bacterial species globally, it remains rare with no previous report in Africa. Methods In this study, an Acinetobacter baumannii isolate cultured from a purulent open septic ulcer on the right breast in a 58-year-old female patient in Kenya was characterized. Bacterial identification and antimicrobial susceptibility testing were conducted using the VITEK 2 system with minimum inhibitory concentrations (MICs) interpreted according to CLSI guidelines 32 nd Edition and whole genome sequencing performed using Illumina and Oxford Nanopore Technology. Genome assembly was performed from long reads using Autocycler and polished with short reads using Polypolish. This was followed by strain typing with MLST, plasmid replicon typing with using BLASTn against AcinetobacterPlasmidTyping database, screening of antibiotic resistance gene (ARGs) using AbritAMR, comparative plasmid analysis with Proksee and functional annotation with Bakta. Results The isolate exhibited resistance to meropenem and displayed a multi-drug resistant (MDR) phenotype showing additional resistance to piperacillin, ticarcillin-clavulanic acid, cefepime, ceftriaxone and levofloxacin. It belongs to sequence type ST52, a rare sequence type globally. The isolate carried four plasmids, two of which are resistance plasmids. The isolate also harbored chromosomal intrinsic resistance genes typical within this lineage, however, additional plasmid-encoded ARGs conferring resistance to multiple antibiotic classes including carbapenem were identified, making it multidrug-resistant. The bla NDM-6 was identified in one of the plasmids with r3-T3 replicon type. Genomic analysis revealed bla NDM-6 was embedded within a Tn 125 -like structure flanked by IS Aba125 elements, consistent with previously described genetic contexts for bla NDM variants in A. baumannii and bla NDM-6 genes in all host species. Conclusion This study presents the first report of bla NDM-6 in Africa. The detection in a rare lineage suggests an independent acquisition via plasmids. Further, it highlights an ongoing evolution of historically susceptible A. baumannii lineages into multidrug-resistant threats. This emphasizes the need for enhanced genomic surveillance in LMICs to monitor the emergence and dissemination of resistance determinants.

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