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. 2024 Aug 6:14:1447933.
doi: 10.3389/fcimb.2024.1447933. eCollection 2024.

FosA3 emerging in clinical carbapenemase-producing C. freundii

Vittoria Mattioni Marchetti  1 , Irene Venturelli  2 , Tiziana Cassetti  2 , Marianna Meschiari  3 , Roberta Migliavacca  1   4 , Ibrahim Bitar  5   6
Affiliations

FosA3 emerging in clinical carbapenemase-producing C. freundii

Vittoria Mattioni Marchetti et al. Front Cell Infect Microbiol. .

Abstract

Fosfomycin (FOS) is an effective antibiotic against multidrug-resistant Enterobacterales, but its effectiveness is reducing. Little is known on the current prevalence of FosA enzymes in low-risk pathogens, such as Citrobacter freundii. The aim of the study was the molecular characterization of a carbapenemase- and FosA-producing C. freundii collected in Italy. AK867, collected in 2023, showed an XDR profile, retaining susceptibility only to colistin. AK867 showed a FOS MIC >128 mg/L by ADM. Based on WGS, AK867 belonged to ST116 and owned a wide resistome, including fosA3, blaKPC-2, and blaVIM-1. fosA3 was carried by a conjugative pKPC-CAV1312 plasmid of 320,480 bp, on a novel composite transposon (12,907 bp). FosA3 transposon shared similarities with other fosA3-harboring pKPC-CAV1312 plasmids among Citrobacter spp. We report the first case of FosA3 production in clinical carbapenemase-producing C. freundii ST116. The incidence of FosA3 enzymes is increasing among Enterobacterales, affecting even low-virulence pathogens, as C. freundii.

Keywords: Citrobacter freundii; carbapenemases; fosA3 gene; fosfomycin; fosfomycin resistance.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Linear map of pfosA3_CFR867 (from 241,351 bp to 296,797 bp) against OW849528.1, MG387191.2, CP137481.1, CP110911.1, CP110891.1, and СР045556.1. Dark blue: HNH endonuclease; yellow: IS; red: AMR genes; light blue: Int1; green: mercury system locus. Light blue shadows refer to 100% identity; gray shadows refer to identity less than 100%.
Figure 2
Figure 2
BRIG circular map of pfosA3_CFR867 against MG387191.2 (turquoise), СР045556.1 (violet), OW849528.1 (yellow), CP110911.1 (green), CP110891.1 (light green), AP018570.2 (fuchsia), CP11611.1 (red), CP103368.1 (purple), CP119050.1 (pink), and CP137193.1 (jade green). At the outer curved segments, blue, fuchsia, yellow, red, light blue and green refer to replication (repA), HNH endonuclease, IS, AMR genes, Int1 and Tra system locus.
Figure 3
Figure 3
SNP-based phylogeny pictured using iTOL v6. Salmon circle grid: AMR genes. At the end of branches, red dots refer to CL3, light blue dots to CL2, and blue dots to CL1. On the squared grid (virulome), red = toxins; green = adhesion; yellow = metabolism; light green = siderophores; lilac = invasion; blue = chemotaxis.
See this image and copyright information in PMC

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