Biology subjects

Prichula, J.

Publications and source records attributed to Prichula, J..

4 recordsLinked to original sources

bioRxiv2025

Efagins evolved independently to target the enterococcal cell wall

Enterococci are major causes of multidrug-resistant infections, and antimicrobials with fundamentally new mechanisms of action are urgently needed. We identify a new class of antibacterial agents, termed efagins, which are chromosomally encoded, phage-related nanomachines that recognize cell wall carbohydrate receptors and inhibit subsets of E. faecalis, E. faecium and other enterococci selectively--a key reason they evaded prior detection. Five natural variants with distinct targeting profiles were identified - four related by sequence divergence, while one appears to have arisen through recombination of the targeting domain, likely from a phage donor. Operons encoding the corresponding carbohydrate receptors are highly variable, accounting for targeting specificity. The efagin targeting domain can be engineered to reprogram them toward alternative receptors, providing a pathway for filling critical coverage gaps. These findings advance efagins as new selective antibacterials with promise for addressing infection and spread of multidrug-resistant enterococcal infection.

microbiology↗

bioRxiv2024

Revisiting the taxonomy of Enterococcus casseliflavus and related species

Enterococcus casseliflavus is a commensal bacterium that can occasionally cause human infections. A concern is that all strains of this species carry the vanC operon on their chromosomes, which reduces susceptibility to vancomycin. Aside from that, the classification of E. casseliflavus remains challenging because it shares up to 99% 16S rRNA sequence identity with other enterococci species. Here, we reassess the taxonomy and genomic diversity of E. casseliflavus and closely related taxa by comprehensively analyzing publicly available genomes to clarify their evolutionary relationships, ecological distributions, and clinical relevance. We retrieved 156 genomes of clinical and non-clinical isolates that showed ANI >90% with E. casseliflavus from public databases. Using ANI, core genome-based phylogeny, and pangenome reconstruction, we consistently identified three well-defined clusters corresponding to E. casseliflavus, E. entomosocium, and E. innesii. Our results indicate that a higher ANI threshold (>96.6%) is required to accurately discriminate between species within this group, as many strains showed more than 95% ANI with multiple species. Our results also support that E. flavescens and E. casseliflavus represent a single species and should be treated as synonyms. Genes related to biocide resistance, metal tolerance, and virulence were identified across the three species. E. casseliflavus exhibited the greatest diversity of resistance determinants. All species harbored the vanC operon associated with intrinsic vancomycin resistance, while two genomes additionally carried the vanD operon linked to high-level glycopeptide resistance. Overall, our findings refine species boundaries and highlight the importance of genome-based approaches for accurate classification and surveillance within the Enterococcus genus.

bioinformatics↗

bioRxiv2023

Global diversity of enterococci and description of 18 novel species

Enterococci are commensal gut microbes of most land animals. They diversified over hundreds of millions of years adapting to evolving hosts and host diets. Of over 60 known enterococcal species, Enterococcus faecalis and E. faecium uniquely emerged in the antibiotic era among leading causes of multidrug resistant hospital-associated infection. The basis for the association of particular enterococcal species with a host is largely unknown. To begin deciphering enterococcal species traits that drive host association, and to assess the pool of Enterococcus-adapted genes from which known facile gene exchangers such as E. faecalis and E. faecium may draw, we collected 886 enterococcal strains from nearly 1,000 specimens representing widely diverse hosts, ecologies and geographies. This provided data on the global occurrence and host associations of known species, identifying 18 new species in the process expanding genus diversity by >25%. The novel species harbor diverse genes associated with toxins, detoxification, and resource acquisition. E. faecalis and E. faecium were isolated from a wide diversity of hosts highlighting their generalist properties, whereas most other species exhibited more restricted distributions indicative of specialized host associations. The expanded species diversity permitted the Enterococcus genus phylogeny to be viewed with unprecedented resolution, allowing features to be identified that distinguish its four deeply rooted clades as well as genes associated with range expansion, such as B-vitamin biosynthesis and flagellar motility. Collectively, this work provides an unprecedentedly broad and deep view of the genus Enterococcus, potential threats to human health, and new insights into its evolution. SIGNIFICANCEEnterococci, host-associated microbes that are now leading drug-resistant hospital pathogens, arose as animals colonized land over 400 million years ago. To globally assess the diversity of enterococci now associated with land animals, we collected 886 enterococcal specimens from a wide range of geographies and ecologies, ranging from urban environments to remote areas generally inaccessible to humans. Species determination and genome analysis revealed host associations from generalists to specialists, and identified 18 new species, increasing the genus by over 25%. This added diversity provided greater resolution of the genus clade structure, identifying new features associated with species radiations. Moreover, the high rate of new species discovery shows that tremendous genetic diversity in Enterococcus remains to be discovered.

microbiology↗

bioRxiv2021

SARS-CoV-2 introduction and lineage dynamics across three epidemic peaks in Southern Brazil: massive spread of P.1

BackgroundGenomic surveillance of SARS-CoV-2 is paramount for understanding viral dynamics, contributing to disease control. This study analyzed SARS-CoV-2 genomic diversity in Rio Grande do Sul (RS), Brazil, including the first case of each Regional Health Coordination and cases from three epidemic peaks. MethodsNinety SARS-CoV-2 genomes from RS were sequenced and analyzed against SARS-CoV-2 datasets available in GISAID for phylogenetic inference and mutation analysis. ResultsSARS-CoV-2 lineages among the first cases in RS were B.1 (33.3%), B.1.1.28 (26.7%), B.1.1 (13.3%), B.1.1.33 (10.0%), and A (6.7%), evidencing SARS-CoV-2 introduction by both international origin and community-driven transmission. We found predominance of B.1.1.33 (50.0%) and B.1.1.28 (35.0%) during the first epidemic peak (July-August, 2020), emergence of P.2 (55.6%) in the second peak (November-December, 2020), and massive spread of P.1 and related sequences (78.4%), such as P.1-like-II, P.1.1 and P.1.2 in the third peak (February-April, 2021). Eighteen novel mutation combinations were found among P.1 genomes, and 22 different spike mutations and/or deletions among P.1 and related sequences. ConclusionsThis study shows the dispersion of SARS-CoV-2 lineages in Southern Brazil, and describes SARS-CoV-2 diversity during three epidemic peaks, highlighting the spread of P.1 and the high genetic diversity of currently circulating lineages. Genomic monitoring of SARS-CoV-2 is essential to guide health authorities decisions to control COVID-19 in Brazil. SummaryNinety SARS-CoV-2 genomes from Rio Grande do Sul, Brazil, were sequenced, including the first cases from 15 State Health Coordination regions and samples from three epidemic peaks. Phylogenomic inferences showed SARS-CoV-2 lineages spread, revealing its genomic diversity.

genomics↗