Biology subjects

Vidal, R. M.

Publications and source records attributed to Vidal, R. M..

5 recordsLinked to original sources

bioRxiv2024

NSP4 mutation T492I drives rapid evolution of SARS-CoV-2 toward Omicron

T492I, a mutation encountered in SARS-CoV-2 nonstructural protein 4 (NSP4), enhances viral replication and alters nonstructural protein cleavage, causing potential evolutionary impacts. Through comprehensive comparative analyses based on evolve-and-resequence experiments of SARS-CoV-2 wild-type and Delta strains with or without T492I, we demonstrate that NSP4 T492I not only increases the mutation rate, but also accelerates the emergence of many mutations characteristic for Omicron variants. Accordingly, viral populations that evolved from ancestors with T492I, show Omicron-biased selective forces and increases in viral replication, infectivity, immune evasion capacity, potentials for cross-species transmission and receptor-binding affinity. Aside from enhanced replication, we observed stronger epistasis regarding viral replication and infectivity in T492I than in S N501Y and NSP6 {Delta}SGF; this facilitates the regulation of mutation types, which can drive fast evolution of Omicron specific mutations. Our results highlight the role of an important replication-enhancing mutation in regulating the evolutionary rates and mutational trends of SARS-CoV-2.

evolutionary biology↗

bioRxiv2023

Antigenic cartography using variant-specific hamster sera reveals substantial antigenic variation among Omicron subvariants

SARS-CoV-2 has developed substantial antigenic variability. As the majority of the population now has pre-existing immunity due to infection or vaccination, the use of experimentally generated animal immune sera can be valuable for measuring antigenic differences between virus variants. Here, we immunized Syrian hamsters by two successive infections with one of eight SARS-CoV-2 variants. Their sera were titrated against 14 SARS-CoV-2 variants and the resulting titers visualized using antigenic cartography. The antigenic map shows a condensed cluster containing all pre-Omicron variants (D614G, Alpha, Delta, Beta, Mu, and an engineered B.1+E484K variant), and a considerably more distributed positioning among a selected panel of Omicron subvariants (BA.1, BA.2, BA.4/5, the BA.5 descendants BF.7 and BQ.1.18; the BA.2.75 descendant BN.1.3.1; and the BA.2-derived recombinant XBB.2). Some Omicron subvariants were as antigenically distinct from each other as the wildtype is from the Omicron BA.1 variant. The results highlight the potential of using variant-specifically infected hamster sera for the continued antigenic characterisation of SARS-CoV-2.

immunology↗

bioRxiv2021

Landscapes and bacterial signatures of mucosa-associated intestinal microbiota in Chilean and Spanish patients with inflammatory bowel disease

Inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohns disease (CD), cause chronic inflammation of the gut, affecting millions of people worldwide. IBD have been frequently associated with an alteration of the gut microbiota, termed dysbiosis, which is generally characterized by an increase in abundance of Proteobacteria such as Escherichia coli, and a decrease in abundance of Firmicutes such as Faecalibacterium prausnitzii (an indicator of a healthy colonic microbiota). The mechanisms behind the development of the IBD and the dysbiosis are incompletely understood. Using samples from colonic biopsies, we studied the mucosa-associated intestinal microbiota in Chilean and Spanish patients with IBD. In agreement with previous studies, microbiome comparison between IBD patients and non-IBD controls indicated that dysbiosis in these patients is characterized by an increase of pro-inflammatory bacteria (mostly Proteobacteria) and a decrease of commensal beneficial bacteria (mostly Firmicutes). Notably, bacteria typically residing on the mucosa of healthy individuals were mostly obligate anaerobes, whereas in the inflamed mucosa an increase of facultative anaerobe and aerobic bacteria was observed. We also identify potential co-occurring and mutually exclusive interactions between bacteria associated with the healthy and inflamed mucosa, which appear to be determined by the oxygen availability and the type of respiration. Finally, we identify a panel of bacterial biomarkers that allow the discrimination between eubiosis from dysbiosis with a high diagnostic performance (96% accurately), which could be used for the development of non-invasive diagnostic methods. Thus, this study is a step forward toward understanding the landscapes and alterations of mucosa-associated intestinal microbiota in patients with IBD.

microbiology↗

bioRxiv2019

Genomic characterization of the non-O1/non-O139 Vibrio cholerae strain that caused a gastroenteritis outbreak in Santiago, Chile, 2018

Vibrio cholerae is a human pathogen, which is transmitted by the consumption of contaminated food or water. V. cholerae strains belonging to the serogroups O1 and O139 can cause cholera outbreaks and epidemics, a severe life-threatening diarrheal disease. In contrast, serogroups other than O1 and O139, denominated as non-O1/non-O139, have been mainly associated with sporadic cases of moderate or mild diarrhea, bacteremia and wound infections. Here we investigated the virulence determinants and phylogenetic origin of a non-O1/non-O139 V. cholerae strain that caused a gastroenteritis outbreak in Santiago, Chile, 2018. We found that this outbreak strain lacks the classical virulence genes harboured by O1 and O139 strains, including the cholera toxin (CT) and the toxin-coregulated pilus (TCP). However, this strain carries genomic islands (GIs) encoding Type III and Type VI secretion systems (T3SS/T6SS) and antibiotic resistance genes. Moreover, we found these GIs are wide distributed among several lineages of non-O1/non-O139 strains. Our results suggest that the acquisition of these GIs may enhance the virulence of non-O1/non-O139 strains that lack the CT and TCP-encoding genes. Our results highlight the pathogenic potential of these V. cholerae strains. DATA SUMMARYSequence data were submitted to GenBank under the accession number SRLP00000000. The authors confirm that all supporting data and protocols have been provided within the article or through supplementary data files. Data statementAll supporting data, code and protocols have been provided within the article or through supplementary data files. Four supplementary tables are available with the online version of this article.

microbiology↗

bioRxiv2019

Immunization of mice with chimeric antigens displaying selected epitopes confers protection against intestinal colonization and renal damage caused by Shiga toxin-producing Escherichia coli (STEC).

Shiga toxin-producing Escherichia coli (STEC) cause diarrhea and dysentery, which may progress to hemolytic uremic syndrome (HUS). Vaccination has been proposed as a preventive approach against STEC infection; however, there is no vaccine for humans and those used in animals reduce but do not eliminate the intestinal colonization of STEC. The OmpT, Cah and Hes proteins are widely distributed among clinical STEC strains and are recognized by serum IgG and IgA in patients with HUS. Here, we develop a vaccine formulation based on two chimeric antigens containing epitopes of OmpT, Cah and Hes proteins against STEC strains. Intramuscular and intranasal immunization of mice with these chimeric antigens elicited systemic and local long-lasting humoral responses. However, the class of antibodies generated was dependent on the adjuvant and the route of administration. Moreover, while intramuscular immunization with the combination of the chimeric antigens conferred protection against colonization by STEC O157:H7 and the intranasal conferred protection against renal damage caused by STEC O91:H21. This pre-clinical study supports the potential use of this formulation based on recombinant chimeric proteins as a preventive strategy against STEC infections.

microbiology↗