Biology subjects

Patricio, D. d. O.

Publications and source records attributed to Patricio, D. d. O..

4 recordsLinked to original sources

bioRxiv2026

Mucin modulates phage infection dynamics and biofilm formation in enteropathogenic Yersinia enterocolitica

Mucosal barriers serve as a multifunctional interface and nutrient-rich habitat for diverse microbes, including bacteria and bacteriophages. Some phages can bind to mucin glycoproteins via carbohydrate-interacting modules and provide an additional layer of mucosal immunity by shielding the underlying epithelium from invading bacteria. However, the role of mucins in shaping phage-bacterium interactions remains poorly understood. We investigated the dynamics between highly pathogenic Yersinia enterocolitica serotype O:8 and its mucus-adherent phage fMtkYen801 under in vitro mucosal environment. We assessed how mucin supplementation, varying phage doses, nutrient and temperature conditions influence phage-bacterium dynamics and biofilm formation. We found that pre-exposure to mucins led to enhanced phage replication in the bacterial host, with a 2-log increase in phage titers, and high abundance of surviving bacteria. Interestingly, mucin glycoproteins also provided Y. enterocolitica a nutrient source and a chemical cue to modulate its growth and biofilm biogenesis. Genomic analysis of phage-resistant bacterial variants revealed mutations in virulence, quorum sensing, and antibiotic resistance genes in both mucin enrichment and control groups, suggesting potential fitness tradeoffs during resistance evolution. Collectively, these findings highlight the importance of mucosal surfaces as an important ecological driver of phage-host interactions in Y. enterocolitica, a significant enteric pathogen, and emphasize the need for investigating these dynamics under complex, physiologically relevant systems to inform better phage therapy strategies against mucosal bacterial infections.

microbiology↗

bioRxiv2025

Mucin-enriched environment shapes bacteriophage protection against Pseudomonas aeruginosa in airway epithelial cells

Mucin hypersecretion, a hallmark of chronic respiratory diseases (CRD), creates a complex microenvironment that reshapes host immunity and microbial behavior. However, its impact on bacteriophage therapy remains poorly understood. Here, we demonstrate that, despite reducing Pseudomonas aeruginosa internalization, exogenous mucin increases bacterial-induced cytotoxicity and inflammation in airway epithelial cells, while driving CRD-like transcriptional changes, including hypoxia and stress responses. Under bacterial culture, mucin selectively downregulates bacterial virulence factors without impairing growth. P. aeruginosa-infecting bacteriophage DMS3vir retains full lytic activity in mucin-rich conditions and, in synergy with mucin, enhances protection against cytotoxicity in epithelial cells. DMS3vir also reduces IL-8 gene expression without triggering antiviral responses. Furthermore, mucin supplementation shapes phage-resistant P. aeruginosa phenotypes, altering colony pigmentation, pyocyanin production, and motility, influencing virulence trade-offs. These findings uncover the dual role of mucins as modulators of infection and sensitizers to phage protection, paving the way for optimized, mucosa-adapted phage therapies in chronic lung diseases.

microbiology↗

bioRxiv2019

Flaviviruses exploit fine-tuning of the interferon response to promote replication

The establishment of a virus infection is the result of the pathogens ability to replicate in a hostile environment generated by the hosts immune system. Here, we found that ISG15 restricts Dengue and Zika viruses replication through the stabilisation of its binding partner USP18. ISG15 expression was necessary to control DV replication driven by both autocrine and paracrine type one interferon (IFN-I) signalling. Moreover, USP18 competes with NS5-mediated STAT2 degradation, a major mechanism for establishment of flavivirus infection. Strikingly, reconstitution of USP18 in ISG15-deficient cells was sufficient to restore the STAT2s stability and restrict virus growth, suggesting that the IFNAR-mediated ISG15 activity is also antiviral. Our results add a novel layer of complexity in the virus/host interaction interface and suggest that NS5 has a narrow window of opportunity to degrade STAT2, therefore suppressing hosts IFN-I mediated response and promoting virus replication. IMPORTANCEDisease is an emergent property that results from a microorganisms ability to replicate in a given host and the latters immune response. Here we describe how the immunoregulatory function of ISG15 (an interferon stimulated gene) affects Dengue and Zika virus replication by occupying a niche used by the virus non-structural protein 5 (NS5) to evade hosts immunity. In the absence of ISG15, NS5 efficiently degrades a main signalling hub of innate immunity (STAT2), leading to cell immune suppression and consequently virus growth. This sheds light into how flaviviruses intimately interact with the host immune system and could lead to a host-based therapy target.

immunology↗

bioRxiv2017

ISG15 induces IL-10 production in human monocytes and is a biomarker of disease severity during active tuberculosis

Interferon stimulated gene 15 (ISG15) deficiency in humans leads to severe interferonopathies and mycobacterial disease, the latter being previously associated to its extracellular cytokine-like activity. Here, we demonstrate a novel role for secreted ISG15 as an IL-10 inducer, unique to human primary monocytes. Employing ex vivo systems analysis of human transcriptome datasets, we observed a significant correlation of ISG15-induced monocyte IL-10 and lymphocyte IFN{gamma} balanced expression. This effect was associated with p38 MAPK and PI3K signalling in healthy volunteers. The specificity and MAPK/PI3K-dependence of ISG15-induced monocyte IL-10 production was confirmed in vitro using CRISPR/Cas9 knockout and pharmacological inhibitors. Moreover, this ISG15/IL10 axis was amplified in leprosy but disrupted in human active tuberculosis (TB) patients. Importantly, ISG15 strongly correlated with inflammation and disease severity during active TB. In conclusion, this study identifies a novel anti-inflammatory ISG15/IL-10 myeloid axis that is disrupted in active TB, revealing a potential biomarker for disease severity in this major human disease.

immunology↗