Biology subjects

Biarnes, M.

Publications and source records attributed to Biarnes, M..

3 recordsLinked to original sources

bioRxiv2026

In vitro efficacy of synthetic antimicrobial peptide SET-M33 against poultry isolates with diverse antimicrobial resistance phenotypes

Antimicrobial resistance is an impactful One Health issue. One of its drivers is the extensive use of antibiotics in both human and animal production systems, and despite regulatory restrictions on antibiotic use in poultry farming, antimicrobial resistance remains a major challenge. Consequently, animals are at higher risk of harder-to-treat diseases and play a role as resistance reservoirs, highlighting the need for alternative antimicrobial strategies. Towards this end, antimicrobial peptides (AMPs) have emerged as promising candidates due to their broad-spectrum activity and lower propensity to induce resistance. However, the effectiveness of AMPs against poultry pathogens, and in particular multi drug-resistant strains, is largely unclear. To tackle this question, we evaluated the synthetic AMP SET-M33 against four species of clinically relevant pathogens in poultry, namely Escherichia coli, Salmonella enterica, Enterococcus faecalis and Enterococcus cecorum. Using a panel of 141 field isolates, we found that SET-M33 broadly inhibited bacterial growth at low micromolar concentrations (median MICs of 2.5 M and 5 M for Gram-negative and Gram-positive strains, respectively), including in multi drug-resistant isolates. To examine the potential impact of SET-M33 on the host, we established a new in vitro co-cultivation system using chicken intestinal organoids. We found that SET-M33 retains its antimicrobial activity in organoid-microbe co-cultures at concentrations that preserved host viability. These findings demonstrate the potential of SET-M33 as a new antimicrobial agent against pathogens in poultry.

microbiology↗

bioRxiv2026

Antibody maturation in germinal centers selects mutants based on BCR-antigen bond mechanical resistance

Antibody maturation in germinal centers (GCs) is traditionally viewed as a process that enhances antigen-binding affinity of B cell receptors (BCR). However, recent studies challenge this paradigm, revealing no systematic antibody affinity improvement during GC selection. Here, we investigate whether mechanical resistance of antibody-antigen bonds, rather than affinity, is the selective parameter driving GC maturation. Using biolayer interferometry measurements for assessing affinity and laminar flow chamber for mechanical resistance, we analyzed three lineages of mouse antibodies generated after immunization with ovalbumin. While affinity changes were heterogeneous, ranging from gains to losses across lineages, mechanical resistance consistently increased after maturation. Bond lifetimes under physiological forces (10-70 pN) converged to similar values across lineages, suggesting a selective pressure for mechanical stability. Functionally, NK cell activation in a surrogate in vitro ADCC assay correlated with bond lifetimes under force, but not with affinity. This indicates that lymphocytes are sensitive to the mechanical stability of antibody-antigen interactions, which may underlie GC selection. Our findings reconcile antibody maturation with the idea of enhanced binding, while aligning with the role of mechanical forces in B cell signaling and antigen uptake. These insights provide a framework for understanding GC biology and may inform the design of therapeutic antibodies.

immunology↗

bioRxiv2025

Bivalency of natalizumab promotes inhibition of dynamic VLA-4 adhesion beyond affinity gain

Natalizumab, a monoclonal IgG4 antibody used in the treatment of multiple sclerosis (MS), inhibits VLA-4 binding to VCAM-1, thereby reducing leukocyte recruitment to inflamed tissues. The intricate mechanisms underlying these effects remain unclear, particularly concerning the heavy-chain shuffling of IgG4. We conducted an in vitro study to quantify the impact of bivalent IgG and monovalent Fab forms of natalizumab on the capture and migration of human primary memory T lymphocytes under shear stress, using VCAM-1 and SDF-1-coated surfaces. IgG natalizumab at concentrations near its cell surface EC50 showed significant of capture and resistance of adherent cells to shear stress, whereas significantly higher doses of Fab natalizumab, up to 100-fold greater than its cell surface EC50, were needed to achieve similar effects. These findings highlight that receptor occupancy alone may not adequately predict the functional outcomes of inhibitor antibodies. For optimal therapeutic effect, inhibition of cell-surface adhesion may require specific kinetic and geometric binding properties of antibodies.

immunology↗