Biology subjects

Dahyot, S.

Publications and source records attributed to Dahyot, S..

3 recordsLinked to original sources

bioRxiv2026

Multi-omics profiling reveals convergent adaptation of urinary Pseudomonas aeruginosa isolates

Pseudomonas aeruginosa is a major opportunistic pathogen, responsible for healthcare-associated urinary tract infections. Its metabolic flexibility and genomic plasticity promote its survival and adaptation in complex environments. Here, we conducted an in-depth analysis of three pairs of sequential P. aeruginosa urinary isolates, named "early" and "late", from three patients to investigate metabolic and phenotypic changes during urinary tract adaptation. An integrated multi-omics approach combining RNA sequencing and metabolomics was performed on isolates grown in human urine (HU) and trypticase soy (TS) medium, and compared with previously published proteomics data. Late isolates showed down-regulation of genes encoding type VI secretion system in both media, while oxidative phosphorylation associated-genes were up-regulated in HU. These late isolates also displayed significant down-regulation of amino-acid metabolism suggesting an increased use of carbon sources available in urine. As previously observed in proteomics, siderophore- and iron-related genes were significantly down-regulated for all late isolates in HU but not in TS, supporting convergent adaptation to the low-iron urinary environment. Metabolomic profiles of HU supernatants from late isolates clustered together, showing common metabolite production in HU. The differential metabolic profile between early and late isolates included phosphatidylcholines, acylcarnitines, biogenic amines and amino-acids, highlighting their importance in urinary adaptation. While long-term survival in HU and TS was similar between isolates, biofilm formation was reduced or lost in late isolates in line with the down-regulation of biofilm-related genes. These findings highlight the transcriptomic and metabolic reprogramming as well as the phenotypic changes occurring during P. aeruginosa adaptation to the urinary tract. ImportancePseudomonas aeruginosa is a major opportunistic bacterial pathogen responsible for healthcare difficult-to-treat urinary tract infections. Understanding how this bacterium adapts and persists in the human urinary tract is essential for improving the management of persistent infections. Through an integrated analysis of six sequential clinical isolates from three patients, this study shows that P. aeruginosa undergoes coordinated metabolic and phenotypic changes that promote survival in the urinary environment. During adaptation, the bacterium reduces traits involved in bacterial competition and biofilm formation while reprogramming its metabolism to the nutrients available in urine. These changes emerged independently in different patients, revealing convergent adaptation to this challenging environment. By identifying biological processes consistently associated with urinary tract persistence, this work provides new insight into the mechanisms that support long-term colonization and highlights adaptive metabolic pathways that may represent future targets for therapeutic intervention.

microbiology↗

bioRxiv2025

Characterization of Staphylococcus lugdunensis biofilm reveals key differences according to clonal lineage and iron availability

To understand the mechanisms involved in the evolutionary success of Staphyloccocus lugdunensis clones, we compared the biofilm-forming ability of representative strains of the seven clonal complexes (CCs) in rich and iron-restricted conditions, and characterized the extracellular matrix (ECM) of two highly biofilm-forming strains under each condition. Over 90% of the 49 S. lugdunensis strains produced biofilm in both conditions, with a level of production depending on the iron availability and clonal lineage. Two behaviors were observed: a significantly higher production in rich medium than in iron-restricted medium for CC1, CC2, and some CC3 strains, and the opposite phenomenon for CC6 ones. Analysis of the ECM of two representative strains using confocal microscopy showed that biofilm of the CC3 strain in rich medium contained similar amounts of proteins, eDNA and polysaccharides while that of CC6 strain was predominantly proteinaceous. Under iron-restricted conditions, biofilm structure and composition of both strains completely differed from those obtained in rich conditions. The proteomic analysis of their biofilm ECM by liquid chromatography coupled to tandem mass spectrometry identified 321 proteins common to both strains, mainly intracellular and in particular ribosomal. Of note, 202 proteins differed between the strains in terms of abundance, with a higher proportion of membrane proteins in the CC3 strain. This study performed on a large cohort of strains shows that S. lugdunensis biofilm-forming capacity is strongly associated with CC and iron availability. This analysis of biofilm-associated proteins in S. lugdunensis opens the way to propose new molecular targets for anti-biofilm strategies. IMPORTANCEThe ability of S. lugdunensis to produce biofilm is considered as a critical virulence factor. As biofilm is strongly associated with persistence and difficult-to-treat infections, characterizing biofilm production and composition, particularly in iron-deficient environments encountered during infection, can provide a better understanding of therapeutic failures. Our work is the first to be carried out on such a large collection of S. lugdunensis clinical strains. It shows that this species is a strong biofilm producer, even in an iron-deficient environment, and that the composition of its matrix varies according to both genetic background of the strain and environmental conditions. Moreover, investigating the biofilms protein matrix of two S. lugdunensis strains provides insights into identification of potential targets for biofilm eradication.

microbiology↗

bioRxiv2023

Are Escherichia coli causing recurrent cystitis just ordinary Uropathogenic E. coli (UPEC) strains?

Specific determinants associated with Uropathogenic Escherichia coli (UPEC) causing recurrent cystitis are still poorly characterized. The aims of this study were (i) to describe genomic and phenotypic traits associated with recurrence using a large collection of recurrent and paired sporadic UPEC isolates, and (ii) to explore within-host genomic adaptation associated with recurrence using series of 2 to 5 sequential UPEC isolates. Whole genome comparative analyses between 24 recurrent cystitis isolates (RCIs) and 24 phylogenetically paired sporadic cystitis isolates (SCIs) suggested a lower prevalence of putative mobile genetic elements (MGE) in RCIs, such as plasmids and prophages. The intra-patient evolution of the 24 RCI series over time was characterized by SNP occurrence in genes involved in metabolism or membrane transport, and by plasmid loss in 5 out of the 24 RCI series. Genomic evolution occurred early in the course of recurrence, suggesting rapid adaptation to strong selection pressure in the urinary tract. However, RCIs did not exhibit specific virulence factor determinants and could not be distinguished from SCIs by their fitness, biofilm formation, or ability to invade HTB-9 bladder epithelial cells. Taken together, these results suggest a rapid but not convergent adaptation of RCIs that involves both strain- and host-specific characteristics. Author summaryThe recurrence of cystitis is a frequent but poorly understood phenomenon. There are currently many hypotheses trying to explain recurrence, but data on large collections of well-characterized clinical isolates are lacking. In order to identify specific recurrence-associated markers, we conducted a large genomic and phenotypic study involving 48 well-characterized cystitis isolates: 24 recurrent cystitis isolates (RCIs) and 24 pairs of isolates causing sporadic cystitis (SCIs). Moreover, we were able to explore intra-host overtime RCI evolution, by analyzing up to 5 sequential UPEC isolates per RCI series. Our results suggest that RCI rapidly adapt to their host through mobile genetic elements loss and SNP accumulation in genes involved in metabolism and membrane transport. However, no convergent genomic nor phenotypic evolution was observed between isolates collected from distinct patients. Taken together, these results suggest a host-shaped evolution of RCIs, highlighting a need for future studies focused on the host-pathogen relationships.

microbiology↗