bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.06.13.659522

Emergence of Dual β-lactam and Colistin Resistance via blaFRI-8 and mcr10.2 co-carriage on an IncFII Family Plasmid in Enterobacter vonholyi

Kovarova, A.·Ryan, K.·Tumeo, A.·McDonagh, F.·Clarke, C.·Cormican, M.·Miliotis, G.
View original source ↗Export metadata ↓

Abstract

ObjectivesEnterobacter vonholyi isolate E323169 represents a rare case of co-carriage of the antimicrobial resistance genes (ARGs) blaFRI-8, mcr-10.2. isolated from a clinical rectal swab. E323169 is one of only 12 available E. vonholyi genomes. To date, and across over two million pathogenic genomes scanned, only three harbour blaFRI-8 and two encode mcr-10.2, yet none exhibit both genes together. This study analyzes the genomic, phenotypic and epidemiological importance of this rare co-occurrence. MethodsSpecies-ID for E323169 was assigned by MALDI-TOF and then re-assigned and confirmed using a multifactorial genomic workflow. Antimicrobial susceptibilities were determined by MIC assay. The genome of E323169 was sequenced on an Illumina-NextSeq-1000, assembled, and annotated for ARGs, virulence factors, and plasmid replicons detection. Comparative phylogenomics used 12 E. vonholyi RefSeq assemblies, and NCBI metadata were analysed for plasmid distributions of blaFRI-8 and mcr-10.2. ResultsE323169 carried six ARGs: four chromosomally encoded (blaACT-91, fosA, oqxA10, oqxB9) and two plasmid-borne (blaFRI-8 and mcr-10.2) co-located on IncFII(p14)_1_p14 replicon. Additional plasmid replicons: Col(MG828)_1 and ColRNAI_1 were also identified. By mining the NCBI Pathogen Detection pipeline, we identified blaFRI-8 on IncFII replicon in E. asburiae JBIWA002, and mcr-10.2 on a multi-replicon (IncFIB/IncFII) plasmid in E. kobei 11778-yvys. ConclusionThis report documents the first E. vonholyi isolate co-harboring blaFRI-8 and mcr-10.2 on a single IncFII family plasmid, showing the widening host range of plasmid-mediated resistance to carbapenems/colistin. No prior similar co-occurrences reported, underscoring its rarity. These findings highlight the urgent need for enhanced clinical screening and genomic surveillance to curb the spread.

Source connections

Explore related subjects

microbiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Kovarova, A., Ryan, K., Tumeo, A., McDonagh, F., Clarke, C., Cormican, M., Miliotis, G.. 2025-06-14. Emergence of Dual β-lactam and Colistin Resistance via blaFRI-8 and mcr10.2 co-carriage on an IncFII Family Plasmid in Enterobacter vonholyi. https://doi.org/10.1101/2025.06.13.659522

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Cryo-EM Structure of Mycobacteriophage D29 Reveals a Specialized Portal-Capsid Junction and a Unique 13-Subunit Baseplate Collar

Mycobacteriophages are promising agents against drug-resistant mycobacterial infections, yet their structural organization and host-recognition mechanisms remain poorly understood. Here, we determined cryo-EM structures of the capsid, connector, tail tube, and baseplate of the lytic, broad-host-range mycobacteriophage D29, revealing a near-complete virion architecture. At the capsid-portal interface, five copies of the previously uncharacterized protein gp19.1 bridge adjacent capsid subunits around the dodecameric portal, potentially reinforcing the symmetry-mismatched vertex. At the baseplate, 13 copies of gp6 assemble into a collar surrounding the sixfold-symmetric gp23-gp27 core. Remarkably, this 6:13 symmetry mismatch is accommodated through six distinct gp6- gp27 interfaces involving 12 gp6 subunits, leaving one subunit largely disengaged from the core. This asymmetric organization produces a tilted, outward-flaring collar that presents an extensive surface with the potential to engage the host cell. Whole-cell binding and plaque-competition assays further implicate the gp6 collar and the flexible trimeric central fiber gp31 in host recognition. Together, these findings reveal distinct structural adaptations at symmetry-mismatched interfaces and provide a structural framework for understanding mycobacteriophage assembly and host engagement.

microbiology↗
bioRxiv2026

A Luciferase Reporter of Ester Prodrug Delivery to the Cytosol of Intracellular Mycobacteria

The bacterial cell envelope restricts access to cytoplasmic targets and is a principal reason that otherwise potent antibacterial compounds fail in cells. Masking an anionic carboxylic acid as an ester is a common way to cross that barrier, but the strategy succeeds only if the target organism also hydrolyzes the ester once the compound arrives. These two requirements, permeation and intracellular unmasking, are rarely measured together in live bacterial cells, and existing reporters cannot specify where unmasking occurred. Here we describe a bioluminescent platform that resolves both steps in real time in live mycobacteria using carboxylate esters of D-luciferin. Luciferase requires that an ester both reach the bacterial cytoplasm and be hydrolyzed there, which makes light a compartment-specific readout of productive delivery. Across a series of alkyl esters in Mycobacterium smegmatis, chain length governed permeation while branching adjacent to the carbonyl governed esterase processing, indicating that the two parameters can be tuned independently. The n-butyl ester gave the strongest signal in broth, in infected macrophages, and in the pathogen Mycobacterium avium, whereas the tert-butyl ester was inert in Mycobacterium avium and unmasking of the whole series was attenuated at phagosomal pH. Ester activation is therefore both species- and compartment-dependent, and masking groups are best selected in the organism and environment in which they must act.

microbiology↗
bioRxiv2026

Flexible phosphorus allocation to the phosphoproteome underpins diatom regulatory adaptations to fluctuating phosphate supply

Diatoms are major drivers of marine phosphorus (P) cycling and are highly adapted to cope with variable P supply. P-starved diatoms can sense increases in P availability within seconds, accumulating this limiting resource through luxury polyphosphate (polyP) storage. Yet, how diatoms coordinate such responses is unknown. Protein phosphorylation is a core mechanism for environmental signal transduction in eukaryotes, but how cells balance investment in protein phosphorylation against competing physiological demands during P limitation is poorly understood. Here, we characterise system-wide remodelling of the Phaeodactylum tricornutum phosphoproteome in response to P deficiency and subsequent resupply. We identify widespread proteome dephosphorylation across 44% of phosphosites, revealing a previously unrecognised P-sparing strategy in marine phytoplankton. Following P resupply, diatoms orchestrate extensive phosphoproteome reprogramming within minutes. We characterise previously unrecognized components for early recovery from P limitation, including a novel environmentally prevalent intracellular H+/phosphate transporter strongly conserved in diverse diatoms. We also identify a vacuolar Ca2+-dependent protein kinase (CDPK) associated with polyP-storage granules. Mutant and inhibitor analyses demonstrate a role for Ca2+- and CDPK-signalling in the regulation of luxury polyP accumulation. Our findings reveal that recovery from P starvation is mediated by rapid phosphoregulatory control of intracellular P trafficking, organellar ATP generation coupled with luxury P storage, enabling diatoms to exploit newly available P and thrive in fluctuating P regimes. Collectively, our study uncovers the phosphoproteome as a flexible intracellular P reservoir and establishes mechanistic links between intracellular P budgeting, signalling and the marine P cycle.

microbiology↗