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The number of deaths caused by antimicrobial resistance was estimated at 1.27 million worldwide in 2019 (1), mainly attributed to 6 bacterial species: Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus [...]

Cefiderocol (FDC), a siderophore-cephalosporin conjugate, is the newest option for treating infection with carbapenem-resistant gram-negative bacteria. We identified a novel mechanism contributing to decreased FDC susceptibility in Klebsiella pneumoniae clinical isolates. The mechanism involves 2 coresident plasmids: pKpQIL, carrying variants of blaKPC carbapenemase gene, and pKPN, carrying the ferric citrate transport (FEC) system. We observed increasing FDC MICs in an Escherichia coli model system carrying different natural pKpQIL plasmids, encoding different K. pneumoniae carbapenemase (KPC) variants, in combination with a conjugative low copy number vector carrying the fec gene cluster from pKPN. We observed transcriptional repression of fiu, cirA, fepA, and fhuA siderophore receptor genes in blaKPC-fec-E. coli cells treated with ferric citrate. Screening of 27,793 K. pneumoniae whole-genome sequences revealed that the fec cluster occurs frequently in some globally distributed different KPC-producing K. pneumoniae clones (sequence types 258, 14, 45, and 512), contributing to reduced FDC susceptibility. [ABSTRACT FROM AUTHOR]

Introduction: The Providencia genus is assuming greater clinical relevance among infections caused by Enterobacterales also because of its intrinsic and acquired resistance to last-resort antibiotics. However, despite having been known and studied for over 50 years, genomics and taxonomy of the Providencia genus are currently undergoing a deep rearrangement. In this study we aim to outline and characterized the P. stuartii species. Methods: We retrieved from the GenBank database all genomes labelled as Providencia and performed a comprehensive genome-based species definition founded on average nucleotide identity (ANI) and on alignment-free approaches. Results: After defining the genomes assuredly identifiable as P. stuartii , we devised a MultiLocus Sequence Typing (MLST) and a core-genome MLST (cgMLST) schemes, based on 7 and 2,296 loci respectively. Discussion: This work hence provides a framework for understanding the role of P. stuartii and of other members of this genus, which should be considered as emerging multidrug-resistant pathogens. [ABSTRACT FROM AUTHOR]