Biology subjects

Brizuela, J.

Publications and source records attributed to Brizuela, J..

3 recordsLinked to original sources

bioRxiv2025

Emergence of zoonotic and multi-drug resistant Streptococcus suis

BackgroundStreptococcus suis is an emerging zoonotic porcine pathogen and a leading cause of adult bacterial meningitis in Southeast Asia, associated with raw pork consumption. Most zoonotic S. suis infections globally are by strains from lineage CC1 carrying a serotype 2 capsule. However, in Thailand, [~]40% of the reported zoonotic infections are caused by two endemic lineages, CC104 and CC233 which also have a serotype 2 capsule. In this study, we aimed to identify the drivers of the emergence and recent evolution of these two lineages. MethodsWe sequenced the whole genomes of 141 Thai S. suis zoonotic and porcine strains isolated over a 15-year period and combined them with a curated global dataset of 2761 published S. suis genomes. Using comparative genomics, Bayesian evolutionary models and multivariate analysis we investigated the emergence of zoonotic potential and multi-drug resistance in CC104 and CC233. FindingsWe estimated recent emergence dates for both CC104 (1990; 95% posterior: 1987-1992) and CC233 (2002; 95% posterior: 2000-2004). Both lineages acquired a serotype capsule 2 from CC1 through a capsule locus switching event, prior to their emergence. Both have also experienced multiple antimicrobial resistance (AMR) acquisition events, with some strains carrying 12 determinants encoding resistance against eight classes of antibiotics. Most importantly, CC104 and CC233 lineages are the first zoonotic lineages to have acquired increased resistance to penicillin and ceftriaxone, which form the standard therapy to treat S. suis infections in humans. InterpretationHorizontal transfer of multiple genomic regions can cause rapid emergence of novel multi-drug-resistant zoonotic S. suis lineages. As S. suis is mainly controlled and treated through the use of antibiotics in both pigs and humans, these findings highlight the urgent need for improved and enhanced surveillance, infection control, and treatments.

microbiology↗

bioRxiv2023

The streptococcal phase-variable Type I Restriction-Modification system SsuCC20p dictates the methylome of Streptococcus suis and impacts virulence

Phase-variable Type I Restriction Modification (RM) systems are epigenetic regulatory systems that have been identified in numerous human bacterial pathogens. We previously showed that an emerging zoonotic lineage of Streptococcus suis acquired a phase-variable Type I RM system named SsuCC20p. The SsuCC20p locus was present in the genome of disease-associated isolates from multiple streptococcal species. This indicates that it is not restricted to S. suis and can be acquired through horizontal gene transfer. We demonstrate that SsuCC20p phase-variability relies on a recombinase present within the locus. In vitro, only SsuCC20p is responsible for the genome methylation profiles that were detected in the representative zoonotic S. suis isolate 861160. In addition, we show that, contrary to previous observations, hsdS genes located downstream of the hsdM gene and the recombinase gene, can contribute to the SsuCC20p genome methylation profile. SsuCC20p locked mutants expressing a single hsdS each showed unique genome methylation profiles. The differential genome methylation of the distinct locked mutants caused phase dependent differences in global gene expression in a growth condition dependent manner. We observed significant differences in virulence between hsdS locked mutants in a zebrafish larvae infection model. These data indicate that the streptococcal phase-variable Type I RM system SsuCC20p can impact bacterial virulence via epigenetic regulation of gene expression and potentially contributes to the zoonotic potential of S. suis. ImportancePhase-variation contributes to the virulence of bacterial pathogens as it allows a single strain to produce phenotypic diverse subpopulations. Phase-variable Restriction Modification (RM) systems are systems that allow for such phase-variation via epigenetic regulation of gene expression levels. The phase-variable RM system SsuCC20p was found in multiple streptococcal species and was acquired by an emerging zoonotic lineage of Streptococcus suis. We show that the phase-variability of SsuCC20p is dependent on a recombinase encoded within the SsuCC20p locus. We characterized the genome methylation profiles of the different phases of SsuCC20p and showed that the differential genome methylation within the phases causes differences in gene expression levels and virulence. Altogether, we show that the acquisition of a phase-variable RM system impacts virulence and can potentially contribute to the zoonotic potential of S. suis. Bacterial pathogens can increase their virulence through acquisition of mobile elements containing epigenetic regulatory systems such as RM systems.

microbiology↗

bioRxiv2020

Bacterial protein domains with a novel Ig-like fold bind human CEACAM receptors

Streptococcus agalactiae, also known as group B Streptococcus (GBS), is the major cause of neonatal sepsis in humans. A critical step to infection is adhesion of bacteria at mucosal surfaces. Though several GBS adhesins have been identified, the host receptor targets of these adhesins remain unknown. We report here that surface-expressed {beta} protein from GBS binds to human CEACAM1 and CEACAM5 receptors. A crystal structure of the complex showed that the IgSF domain in {beta} represents a novel Ig-fold subtype called IgI3, in which unique features allow binding to CEACAM1. Bioinformatic assessments revealed that this newly identified IgI3 fold is not exclusively present in GBS. Instead, the IgI3 fold is predicted to be present in adhesins from other clinically important human pathogens. We confirmed the interaction between CEACAM1 and the predicted IgI3-containing adhesin in two different streptococcal pathogens. Overall, our results indicate that the IgI3 fold could provide a broadly applied mechanism for bacteria to target CEACAMs.

microbiology↗