Biology subjects

Buffoni, M.

Publications and source records attributed to Buffoni, M..

3 recordsLinked to original sources

bioRxiv2026

Post-transfer instability, not initial transfer, limits dissemination of IncI1-blaCTX-M-1 plasmids between chicken and human Escherichia coli.

Plasmids are key vectors in the dissemination of antibiotic resistance genes. Within Escherichia coli, IncI1 plasmids carrying blaCTX-M-1 significantly contribute to extended-spectrum beta-lactamase (ESBL) resistance. To investigate their zoonotic dissemination potential, we compared the conjugative transfer rates, post-transfer stability, and short-term evolution of two IncI1-blaCTX-M-1 plasmids transferred from their original chicken E. coli host to a panel of chicken and human E. coli. In vitro conjugation assays revealed that transfer rates were not affected by recipient host origin or temperature and were primarily governed by recipient genotype. However, post-transfer plasmid loss rates were host-dependent, with four-fold higher loss rates in human than chicken-derived transconjugants. The total number of mutations accumulated post-acquisition was determined by the identity of the specific plasmid rather than the host origin, with each plasmid following a distinct evolutionary trajectory involving convergent parallel deletions. Specifically, one trajectory involved the loss of genes associated with plasmid stability, observed more frequently in human than in chicken strains, while the other involved the loss of part of the conjugation machinery. Our findings show that, although these plasmids transfer easily between bacteria from chicken to human hosts, they are less stable in their new host environment, which may restrict their overall spread. A comprehensive One Health risk assessment must consider these critical downstream dynamics of plasmid stability and host-specific evolution.

microbiology↗

bioRxiv2025

Characterization of genetically novel chimeric plasmids from Salmonella Heidelberg conferring multi-drug resistance and increased pathogenicity

Salmonella enterica serotype Heidelberg (S. Heidelberg) is a significant cause of human salmonellosis, with resistance to extended-spectrum cephalosporins posing challenges for clinical management. In this study, we genetically and functionally characterized six plasmids isolated from distinct PFGE-types of S. Heidelberg previously reported in The Netherlands, revealing a chimeric IncC-I1a plasmid that shares similarities with the epidemic pESI plasmid identified in emergent S. Infantis isolates. Our analysis showed the accumulation of genetic determinants conferring resistance to antibiotics (blaCMY-2, tetA and sul2) and heavy metals (mer operon), as well as enhanced pathogenicity (Yersinia high-pathogenicity island). All these elements are located on a stable non-conjugative but likely mobilizable plasmid backbone that imposes only a marginal fitness cost on its bacterial host. This convergence of multidrug resistance and pathogenicity likely enhances bacterial adaptability and virulence, undermining control strategies based solely on reducing selective pressure. The emergence and dissemination of such hybrid plasmids represent an increasing threat to both public and animal health, analogous to that posed by pESI-like plasmids, and underscore the urgent need for integrated genomic surveillance and risk assessment, as their continued expansion could complicate antimicrobial therapy and containment efforts during Salmonella outbreaks.

microbiology↗

bioRxiv2020

Allele-specific collateral and fitness effects determine the dynamics of fluoroquinolone-resistance evolution

Collateral sensitivity (CS), which arises when resistance to one antibiotic increases sensitivity towards other antibiotics, offers novel treatment opportunities to constrain or reverse the evolution of antibiotic-resistance. The applicability of CS-informed treatments remains uncertain, in part because we lack an understanding of the generality of CS effects for different resistance mutations, singly or in combination. Here we address this issue in the Gram-positive pathogen Streptococcus pneumoniae by measuring collateral and fitness effects of clinically relevant gyrA and parC alleles, and their combinations, that confer resistance to fluoroquinolones. We integrated these results in a mathematical model which allowed us to evaluate how different in silico combination treatments impact the dynamics of resistance evolution. We identified common and conserved CS effects of different gyrA and parC alleles; however, the spectrum of collateral effects was unique for each allele or allelic pair. This indicated that allelic identity can impact the evolutionary dynamics of resistance evolution during monotreatment and combination treatment. Our model simulations, which included the experimentally derived antibiotic susceptibilities and fitness effects, and antibiotic specific pharmacodynamics, revealed that both collateral and fitness effects impact the population dynamics of resistance evolution. Overall, we provide evidence that allelic identity and interactions can have a pronounced impact on collateral effects to different antibiotics and suggest that these need to be considered in models examining CS-based therapies. SignificanceA promising strategy to overcome the evolution of antibiotic resistant bacteria is to use collateral sensitivity-informed antibiotic treatments that rely on cycling or mixing of antibiotics, such that that resistance towards one antibiotic confers increased sensitivity to the other. Here, focusing on multi-step fluoroquinolone resistance in Streptococcus pneumoniae, we show that antibiotic-resistance induces diverse collateral responses whose magnitude and direction are determined by allelic identity. Using mathematical simulations, we show that these effects can be exploited via combination treatment regimens to suppress the de novo emergence of resistance during treatment.

microbiology↗