Genomic Characterization of 16S rRNA Methyltransferase-Producing Enterobacterales Reveals the Emergence of Klebsiella pneumoniae ST6260 Harboring rmtF, rmtB, bla[sub.NDM-5], bla[sub.OXA-232] and bla[sub.SFO-1] Genes in a Cancer Hospital in Bulgaria

• Published in: Antibiotics (Basel) 2024-10, Vol.13 (10)
• Main Authors: Sabtcheva, Stefana, Stoikov, Ivan, Georgieva, Sylvia, Donchev, Deyan, Hodzhev, Yordan, Dobreva, Elina, Christova, Iva, Ivanov, Ivan N
• Format: Article
• Language: English
• Subjects: DNA sequencing; Drug resistance in microorganisms; Enterobacter; Enterobacteriaceae; Genetic aspects; Identification and classification; Methyltransferases; Nucleotide sequencing; Ribosomal RNA; Risk factors
• ISSN: 2079-6382; 2079-6382
• DOI: 10.3390/antibiotics13100950

Background: Acquired 16S rRNA methyltransferases (16S-RMTases) confer high-level resistance to aminoglycosides and are often associated with β-lactam and quinolone resistance determinants. Methods: Using PCR, whole-genome sequencing and conjugation experiments, we conducted a retrospective genomic surveillance study of 16S-RMTase-producing Enterobacterales , collected between 2006 and 2023, to explore transmission dynamics of methyltransferase and associated antibiotic resistance genes. Results: Among the 10,731 consecutive isolates, 150 (1.4%) from 13 species carried armA (92.7%), rmtB (4.7%), and rmtF + rmtB (2.7%) methyltransferase genes. The coexistence of extended-spectrum β-lactamase (bla [sub.CTX-M-3/15] , bla [sub.SHV-12] , bla [sub.SFO-1] ), carbapenemase (bla [sub.NDM-1/5] , bla [sub.VIM-1/4/86] , bla [sub.OXA-48] ), acquired AmpC (bla [sub.CMY-2/4/99] , bla [sub.DHA-1] , bla [sub.AAC-1] ), and plasmid-mediated quinolone resistance (qnrB , qnrS , aac(6′)-Ib-cr ) genes within these isolates was also detected. Methyltransferase genes were carried by different plasmids (IncL/M, IncA/C, IncR, IncFIB, and IncFII), suggesting diverse origins and sources of acquisition. armA was co-transferred with bla [sub.CTX-M-3/15] , bla [sub.NDM-1] , bla [sub.VIM-4/86] , bla [sub.OXA-48] , bla [sub.CMY-4] , aac(6′)-Ib-cr , qnrB , and qnrS , while rmtF1 was co-transferred with bla [sub.SFO-1] , highlighting the multidrug-resistant nature of these plasmids. Long-read sequencing of ST6260 K. pneumoniae isolates revealed a novel resistance association, with rmtB1 and bla [sub.NDM-5] on the chromosome, bla [sub.OXA-232] on a conjugative ColKP3 plasmid, and rmtF1 with bla [sub.SFO-1] on self-transmissible IncFIB and IncFII plasmids. Conclusions: The genetic plasticity of plasmids carrying methyltransferase genes suggests their potential to acquire additional resistance genes, turning 16S-RMTase-producing Enterobacterales into a persistent public health threat.