Biology subjects

Berti, V.

Publications and source records attributed to Berti, V..

3 recordsLinked to original sources

bioRxiv2026

Chromosomal integration of blaCTX-M redefines the evolutionary trajectory of antibiotic resistance in E. coli through lineage-structured expansion

The global CTX-M pandemic is considered a plasmid-driven phenomenon, yet chromosomal integration of blaCTX-M has been reported in various settings. Screening 451,174 publicly available E. coli genomes and retaining 2,269 CTX-M-E. coli long-read or hybrid assemblies, we found that 33.5% carried at least one chromosomally integrated blaCTX-M. Chromosomal integration was strongly structured by E. coli lineage and CTX-M variant, reaching 68.5% in ST38 and 43.9% in ST131. In the latter, integration rates varied between subclades with modelling, suggesting recent acceleration within the ST131-C2 subclade. Additional resistance genes were frequently co-integrated with blaCTX-M (33%), with architectures largely inherited from plasmid-borne structures. Integrations were mainly ISEcp1- or IS26-mediated (77.3% and 18.9%, respectively) and occurred across the entire E. coli chromosome without spared zones. blaCTX-M chromosomal integration is a widespread, lineage-structured component of the CTX-M pandemic, providing stable vertical inheritance that complements or may supplant plasmid-mediated dissemination in successful ESBL-E. coli clones.

microbiology↗

bioRxiv2025

Influence of iron uptake systems on cefiderocol activity in Escherichia coli: at the crossroads of antibiotic resistance and virulence

Cefiderocol (FDC) is a new siderophore-conjugated cephalosporin that enters the periplasm via iron transport systems. However, the specific contribution of individual iron uptake pathways to FDC activity remains unclear. We investigated the role of 12 iron acquisition systems using several Escherichia coli strain collections. FDC MICs were determined in iron-depleted and iron-supplemented media for E. coli mutants (Keio and pathogenic island [PAI]-deleted collections) and for clinical wild-type or TEM-producing E. coli (WT/TEM-Ec) and NDM-producing (NDM-Ec) isolates. The distribution of iron uptake genes was assessed in these isolates. In addition, fec operon prevalence and genomic location were investigated in E. coli genomes from EnteroBase and RefSeq databases. Among Keio and 536-PAI-deleted mutants, only {Delta}cirA and {Delta}fiu (enterobactin system) showed increased FDC MICs (8- and 3-fold, respectively), while {Delta}fecA and {Delta}fecB had lower MICs (3-fold decrease). The fec operon, a known extraintestinal virulence factor, was significantly more prevalent in isolates with FDC MICs above median than in those with MICs below (94% vs. 38% in WT/TEM-Ec; 100% vs. 0% in NDM-Ec). According to EUCAST breakpoints, 66.7% of fec-positive NDM-Ec were resistant to FDC while none of the fec-negative were. The fec operon was found in 46.5% of E. coli genomes, including virulent clones (ST131, 77%) and was mostly chromosome-borne (99%). Plasmid-borne fec closely resembled that of Enterobacter hormaechei, suggesting interspecies transfer. Our findings highlight the role of Fec in reducing FDC susceptibility and promoting resistance in NDM-producing E. coli. They challenge the virulence-resistance trade-off demonstrating the liaisons dangereuses between iron and antibiotics.

microbiology↗

bioRxiv2020

Mycobacterium tuberculosis micro-diversity promotes intra-macrophagic persistence and antibiotic tolerance

Mycobacterium tuberculosis (Mtb) genetic micro-diversity in clinical isolates may underline mycobacterial adaptive response during the course of tuberculosis (TB) and provide insights to anti-TB treatment response and emergence of resistance. Herein we followed within-host evolution of Mtb clinical isolates in a cohort of patients with delayed Mtb culture conversion. We captured the genetic diversity of both the initial and the last Mtb isolate obtained in each patient, by focusing on minor variants detected as unfixed single nucleotide polymorphisms (SNPs). To unmask antibiotic tolerant sub-populations, we exposed the last Mtb isolate to rifampicin (RIF) prior to whole genome sequencing analysis. We were able to detect unfixed SNPs within the Mtb isolates for 9/12 patients, and non-synonymous (ns) SNPs in 6/12 patients. Furthermore, RIF exposure revealed 8 additional unfixed nsSNP unlinked to drug resistance. To better understand the dynamics of Mtb micro-diversity during the course of TB, we investigated the variant composition of a persistent Mtb clinical isolate before and after controlled stress experiments chosen to mimic the course of TB disease. A minor variant, featuring a particular mycocerosates profile, became enriched during both RIF exposure and macrophage infection. The variant was associated with drug tolerance and intracellular persistence, consistent with the pharmacological modeling predicting increased risk of treatment failure. A thorough study of such variants, not necessarily linked to canonical drug-resistance and which may be able to promote anti-TB drug tolerance, may be crucial to prevent the subsequent emergence of resistance. Taken together, the present findings support the further exploration of Mtb micro-diversity as a promising tool to detect patients at risk of poorly responding to anti-TB treatment, ultimately allowing improved and personalized TB management. Author summaryTuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb), bacteria that are able to persist inside the patient for many months or years, thus requiring long antibiotic treatments. Here we focused on TB patients with delayed response to treatment and we performed genetic characterization of Mtb isolates to search for sub-populations that may tolerate anti-TB drugs. We found that Mtb cultured from 9/12 patients contained different sub-populations, and in vitro drug exposure revealed 8 other sub-populations, none related to known drug-resistance mechanisms. Furthermore, we characterized a Mtb variant isolated from a sub-population growing in the presence of rifampicin (RIF), a major anti-TB drug. We found that this variant featured a modified lipidic envelope, and that it was able to develop in the presence of RIF and inside human macrophage cells. We performed pharmacological modelling and found that this kind of variant may be related to a poor response to treatment. In conclusion, searching for particular Mtb sub-populations may help to detect patients at risk of treatment failure and provide additional guidance for TB management.

microbiology↗