Biology subjects

Nuccio, S.-P.

Publications and source records attributed to Nuccio, S.-P..

6 recordsLinked to original sources

bioRxiv2026

Targeting catecholate siderophore systems enables precision depletion of gut enterobacteria during colitis

Adherent-invasive Escherichia coli (AIEC) is frequently isolated from the dysbiotic gut microbiome in inflammatory bowel disease and is implicated in disease progression, highlighting its potential as a therapeutic target. Here we show that iron acquisition is essential for AIEC colonization of the inflamed gut. Mechanistically, four catecholate siderophore receptors act redundantly to support AIEC growth under iron-limited conditions and during colitis. Immunization of colitis-prone Il10-/- mice against catecholate siderophores reduced intestinal AIEC colonization, particularly its association with the mucosa, while largely preserving overall gut microbiome composition. Longitudinal metagenomic profiling identified immunization-associated shifts in Akkermansiaceae and Lactobacillaceae, and experiments in gnotobiotic Il10-/- mice demonstrated that Limosilactobacillus reuteri, a member of the Lactobacillaceae, limited AIEC colonization, whereas Akkermansiaceae exacerbated disease. Our findings establish catecholate siderophore-mediated iron acquisition as a therapeutic target in AIEC and provide proof-of-principle that virulence-targeted immunization can selectively antagonize a disease-associated bacterium while preserving the gut microbiota

microbiology↗

bioRxiv2025

Commensal Escherichia coli colonization triggers Peyer's patch development

The gut microbiota plays a pivotal role in shaping mucosal immunity, yet the specific microbes contributing to lymphoid tissue development remain poorly defined. Here, we identify Escherichia coli, a pioneer commensal bacterium, as a key driver of naive B cell accumulation in gut Peyers patches and lamina propria via a CXCR2-dependent mechanism. We show that E. coli promotes B cell recruitment through the production of curli amyloid fibers, which signal via Toll-like receptor 2 (TLR2). Notably, this effect extends beyond the neonatal period, revealing a broader temporal window for microbial modulation of mucosal immune development. These findings reveal a previously unrecognized role for a defined gut commensal bacterium and its molecular products in orchestrating the formation of gut-associated lymphoid tissue and B cell recruitment.

microbiology↗

bioRxiv2024

PgtE protease enables virulent Salmonella to evade C3-mediated serum and neutrophil killing

Non-typhoidal Salmonella serovars, such as Salmonella enterica serovar Typhimurium (STm), are a leading cause of inflammatory diarrhea in otherwise healthy individuals. Among children, the elderly, and immunocompromised individuals, STm can spread to systemic sites and cause potentially lethal bacteremia. Phagocytic cells and the immune complement system are pivotal to preventing the dissemination of STm. PgtE, an STm outer membrane protease, has been previously described to cleave over a dozen mammalian protein substrates in vitro, including complement protein C3. However, these activities have mostly been observed with mutant, avirulent strains with a truncated O-antigen that renders bacteria sensitive to complement killing. Here, we report that virulent STm utilizes PgtE to evade complement-mediated killing in vivo. The wild-type pathogen increases pgtE expression and PgtE proteolytic function within macrophages and in macrophage-like in vitro growth conditions, concomitant with physiologic O-antigen shortening in these environments. Furthermore, we found that wild-type STms resistance to complement-mediated serum and neutrophil killing is PgtE-dependent. We propose that PgtE promotes the systemic spread of STm by acting as a second line of defense against complement when STm escapes from a macrophage.

microbiology↗

bioRxiv2021

CCL28 modulates neutrophil responses and impacts the trajectory of mucosal infections

The chemokine CCL28 is highly expressed in mucosal tissues, but its role during infection is not well understood. Here we show that CCL28 promotes neutrophil accumulation to the gut of mice infected with Salmonella and to the lung of mice infected with Acinetobacter. Neutrophils isolated from the infected mucosa expressed the CCL28 receptors CCR3 and, to a lesser extent, CCR10, on their surface. The functional consequences of CCL28 deficiency were different between the two infections, as Ccl28-/- mice were highly susceptible to Salmonella gut infection, but highly resistant to otherwise lethal Acinetobacter lung infection. In vitro, unstimulated neutrophils harbored pre-formed intracellular CCR3 that was rapidly mobilized to the cell surface following phagocytosis or inflammatory stimuli. Moreover, CCL28 stimulation enhanced neutrophil antimicrobial activity, production of reactive oxygen species, and formation of extracellular traps, all processes that were largely dependent on CCR3. Consistent with the different outcomes in the two infection models, neutrophil stimulation with CCL28 boosted the killing of Salmonella but not of Acinetobacter. CCL28 thus plays a critical role in the immune response to mucosal pathogens by increasing neutrophil accumulation and activation, which can enhance pathogen clearance but also exacerbate disease depending on the mucosal site and the infectious agent.

immunology↗

bioRxiv2020

Siderophore-mediated zinc acquisition enhances enterobacterial colonization of the inflamed gut.

Zinc is an essential cofactor for bacterial metabolism, and many Enterobacteriaceae express the zinc transporters ZnuABC and ZupT to acquire this metal in the host. Unexpectedly, the probiotic bacterium Escherichia coli Nissle 1917 exhibited appreciable growth in zinc-limited media even when these transporters were deleted. By utilizing in vitro and in vivo studies, as well as native spray metal infusion mass spectrometry and ion identity molecular networking, we discovered that Nissle utilizes yersiniabactin as a zincophore. Indeed, yersiniabactin enables Nissle to scavenge zinc in zinc-limited media, to resist calprotectin-mediated zinc sequestration, and to thrive in the inflamed gut. Moreover, we discovered that yersiniabactins affinity for iron or zinc changes in a pH-dependent manner, with higher affinity for zinc as the pH increased. Altogether, we demonstrate that siderophore metal affinity can be influenced by the local environment and reveal a mechanism of zinc acquisition available to many commensal and pathogenic Enterobacteriaceae.

microbiology↗

bioRxiv2019

Systematic analyses of factors required for adhesion of Salmonella enterica serovar Typhimurium to corn salad (Valerianella locusta)

Salmonella enterica is a foodborne pathogen leading to gastroenteritis and is commonly acquired by consumption of contaminated food of animal origin. However, numbers of outbreaks linked to the consumption of fresh or minimally processed food of non-animal origin are increasing. New infection routes of S. enterica by vegetables, fruits, nuts and herbs have to be considered. This leads to special interest in S. enterica interactions with leafy products, e.g. salads, that are consumed unprocessed. The attachment of S. enterica to salad is a crucial step in contamination, but little is known about the bacterial factors required and mechanisms of adhesion. S. enterica possesses a complex set of adhesive structures whose functions are only partly understood. Potentially, S. enterica may deploy multiple adhesive strategies for adhering to various salad species, and other vegetables. Here, we systematically analyzed the contribution of the complete adhesiome, of LPS, and of flagella-mediated motility of S. enterica serovar Typhimurium (STM) in adhesion to corn salad. We deployed a reductionist, synthetic approach to identify factors involved in the surface binding of STM to leaves of corn salad with particular regard to the expression of all known adhesive structures using the Tet-on system. This work reveals the contribution of Saf fimbriae, type 1 secretion system-secreted BapA, an intact LPS, and flagella-mediated motility of STM in adhesion to corn salad leaves. Importance Human gastrointestinal pathogens are often transmitted by animal products, but recent outbreaks show increasing importance of vegetables as source of infection by pathogenic E. coli or Salmonella enterica. The mechanisms of binding of S. enterica to vegetables such as salad are only poorly understood. We established an experimental model system to systematically investigate the role of adhesive structures of S. enterica serovar Typhimurium in binding to corn salad leaves. The contributions of all members of the complex adhesiome, flagella, and O-antigen were evaluated. We identified that Saf fimbriae, type 1 secretion system-secreted BapA, an intact LPS, and flagella-mediated motility contribute to adhesion of Salmonella to corn salad leaves. These results will enable future investigations on factors contributing to contamination of vegetables under agricultural conditions.

microbiology↗