Biology subjects

Bertola, A.

Publications and source records attributed to Bertola, A..

5 recordsLinked to original sources

bioRxiv2026

Competition against the intestinal microbiota selects for pathoadaptive traits in ESBL E. coli

The intestinal tract is a reservoir for Extended-Spectrum {beta}-Lactamase (ESBL)-producing Escherichia coli. Asymptomatic gut colonization by these pathobionts represents a major risk for extraintestinal infections. Despite clinical relevance, the genetic basis of gut colonization by ESBL E. coli remains poorly understood. Here, we determined how the microbiota shapes the fitness landscape of diverse ESBL E. coli strains, defining the functional requirements for intestinal colonization. In microbiota-depleted hosts, colonization relies mostly on metabolic functions. In contrast, in mice harbouring a microbiota, pathoadaptive functions associated with adhesion and biofilm formation are dominant determinants of E. coli fitness, together with accessory virulence functions. Consistent with these observations, experimental evolution in mice reveals convergent adaptation of ESBL E. coli to the presence of a complex microbiota through enhanced adhesion. These findings establish the microbiota as a major ecological driver of pathoadaptation in antibiotic-resistant pathobionts.

microbiology↗

bioRxiv2025

CSF1R regulates monocyte subset differentiation and intracellular metabolism.

Monocytes are key circulating effectors of vascular homeostasis, innate immunity and inflammation. Following their generation in mouse bone marrow, classical (Ly6Chigh) monocytes are mobilized into the blood circulation where they mature into non-classical (Ly6Clow) patrolling monocytes or are recruited into peripheral tissues where they differentiate into tissue resident or inflammatory macrophages. Monocytes and macrophages express CSF1R (CD115), the receptor for lineage-specific growth factors CSF1 and IL34. Here, we report that acute CSF1R blockade or genetic deletion negatively interferes with monocyte intracellular metabolism and reduces blood Ly6Clow monocytes in part by blunting differentiation of Ly6Chigh monocytes. Based upon lineage-specific deletion of GFPT1 (Glutamine-Fructose-6-Phosphate Transaminase 1), the hexosamine biosynthetic pathway (HBP) is identified as a novel regulator of CSF1R expression and monocyte subset diversity. Our findings provide new insights into the link between CSF1R signaling, metabolic regulation, and monocyte survival and differentiation.

immunology↗

bioRxiv2025

DMB labelling for detection and analysis of capsular polysaccharides

Bacterial capsules are major virulence factors enabling systemic infection by undermining innate and adaptive immunity. Capsular polysaccharides are also the antigen in some of the most successful antibacterial vaccines - including the pneumococcal, neisserial and Hib conjugate vaccines. However, it remains exceptionally challenging to study capsules, primarily due to their high chemical diversity and the limited methods available for their detection and analysis. We describe a robust biochemical method for detection and analysis of ABC transporter-dependent capsular polysaccharides, a major class of capsules that are associated with extraintestinal pathogenic Escherichia coli (ExPEC). The method involves release and fluorescent tagging of polysaccharides from the cell surface. Anion exchange chromatography of labelled samples reveals the presence, relative abundance, and length-distribution of these diverse polysaccharide antigens. The method provides a modern approach to detecting the capsule phenotype, bridging a critical gap left by the decline of serotyping assays. It will enhance our understanding of fundamental capsule biology and advance the development of capsule-targeting vaccines.

biochemistry↗

bioRxiv2024

CD226+ adipose tissue macrophages arise from MDP-derived monocytes and regulate lipid metabolism.

Macrophages are innate immune cells present in all tissues, in which they participate in immune responses and maintenance of tissue homeostasis. They develop either from embryonic precursors or from circulating monocytes, and their origin impacts their functions. We previously observed robust recruitment of monocytes to brown adipose tissue in which they could differentiation into two distinct macrophage subsets identifiable by CD206 or CD226 expression. In the present study, we investigated monocyte differentiation pathways in brown adipose tissue and the function of monocyte-derived macrophages. Fate mapping analysis revealed a low contribution of GMP- and a high contribution of MDP-derived monocytes to the CD226high macrophage subset. Importantly, adoptive transfer experiments demonstrate that MDP- but not GMP-derived monocytes are pre-conditioned to give rise to CD226high macrophages. We found that MDP-derived CD226high macrophages were also present in other tissues including peritoneal cavity, adrenal glands and all adipose depots. CD226high macrophages were regulated by both GM-CSF and CSF1R. Genetic depletion of CD226high macrophages caused increased BAT and plasma triglyceride content. We thus identify CD226high MDP-derived macrophages as a new myeloid cell type conserved across tissues and tied to lipid metabolism homeostasis.

immunology↗

bioRxiv2023

Phenotypic heterogeneity drives phage-bacteria coevolution in the intestinal tract

Phenotypic heterogeneity in bacteria can generate reversible resistance against various stressors, including predation by phages. This allows mixed populations of phenotypically resistant and sensitive bacteria to coexist with virulent phages. However, it remains unclear if these dynamics prevent the evolution of genetic resistance in bacteria and how they affect the evolution of phages. In this work, we focus on bistable alterations of the O-antigen (known as phase variation) in Salmonella Typhimurium (S.Tm) to study how heterogeneous phenotypic resistance affects phage-bacteria coevolution. Our findings reveal that phase variation allows a stable coexistence of S.Tm with a virulent T5-like phage in vitro. This coexistence is nevertheless short-lived when S.Tm and the phage interact within the intestinal tract of mice. In this context, the phage evolves to also infect phenotypically resistant S.Tm cells, incidentally altering infectivity on other Salmonella serovars. In return, the broader host range of the evolved phages drives the evolution of genetic resistance in S.Tm, which results in phage extinction. This work demonstrates that phenotypic heterogeneity profoundly influences the antagonistic coevolution of phages and bacteria, with outcomes intricately tied to the ecological context.

microbiology↗