Comparative genomics of carbapenemase-producing Morganella spp.

Background Morganella are opportunistic pathogens involved in various infections. In Morganella, intrinsic resistance to multiple antibiotics including colistin combined with the emergence of carbapenemase-producers (CP) strongly limits the antimicrobial armamentarium. Methods From 2013 to 2021, 172 highly drug-resistant (XDR) Morganella isolates from 8 European countries and Canada, two reference strains from the Pasteur Institute collection and two susceptible isolates were characterized by WGS, antimicrobial susceptibility testing and biochemical tests. Complete genomes from Genbank (n=103) were included for genomic analysis. Intrinsic resistance mechanism to polymyxins was deciphered by combining genetic analysis with mass spectrometry on the lipid A. Findings Morganella could be separated into 4 species named M. psychrotolerans, M. sibonii, M. morganii and a new species represented by a unique strain. Morganella morganii included two subspecies: M. morganii subsp. morganii (the most prevalent) and M. morganii subsp. intermedius. Intrinsic resistance to tetracycline and conservation of metabolic pathways correlated this refined taxonomy. CP were mostly identified among five high-risk clones of M. morganii subsp. morganii. A single nucleotide polymorphism (SNP) cut-off of 100 was used to decipher outbreaks involving this species. Cefepime-zidebactam and ceftazidime-avibactam were the most potent antimicrobials towards the 172 XDR Morganella spp. isolates of our collection (including 145 CP) except for metallo-beta-lactamase-producers. The intrinsic resistance to polymyxins corresponds to the addition of L-Ara4N on the lipid A. Interpretation This global characterization of the widest collection of XDR Morganella spp. highlighted the need to clarify the taxonomy, deciphered intrinsic resistance mechanisms and paved the way for further genomic comparisons. ### Competing Interest Statement The authors have declared no competing interest.