Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2021.11.12.468441

Recombinant Group A Carbohydrate backbone embedded into Outer Membrane Vesicles is a potent vaccine candidate targeting Group A Streptococcus from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis

Ajay Castro, S.·Thomson, S.·Zorzoli, A.·Meyer, B. H.·Reglinski, M.·Dorfmueller, H. C.
View original source ↗Export metadata ↓

Abstract

BackgroundGroup A Streptococcus (GAS) are responsible for a wide range of human-exclusive infections, annually killing more than 500,000 people. Antibiotic resistance incidence of invasive GAS tripled in the past decade and emphasises the need to develop a universal GAS vaccine. We have produced, for the first time, a recombinant polyrhamnose backbone (pRha), a validated universal GAS vaccine candidate. E. coli outer membrane vesicles (OMVs) carrying pRha were investigated for their immunogenicity and efficacy in an animal model. MethodsOMVs decorated with pRha were administered to C57BL/6J mouse and rabbit models. Flow cytometry, ELISA, Luminex, immunofluorescence microscopy and serum bactericidal assay assays were conducted to investigate the ability of pRha-specific antibodies to recognise and kill clinical (hypervirulent) GAS strains. ResultsOur results suggest that pRha-OMVs induce specific antibodies which recognise Group A Carbohydrate (GAC) from S pyogenes and S. dysgalactiae subsp. equisimilis. Increased IgG levels correlate with increased bactericidal killing of the hypervirulent GAS M89 strain. Elevated IL-17a from pRha-OMV-immunised splenocytes indicates possible stimulation of long-term memory immune cells. ConclusionWe are the first to report efficacy and potency of this unique, exogenously produced polysaccharide, pRha, in the induction of humoral-mediated immune responses to GAS. TopicStreptococcus pyogenes, immunoglobulins, polysaccharides, opsonophagocytosis, acute rheumatic fever, M protein, invasive Group A Streptococcus, hyaluronic acid

Explore related subjects

microbiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Ajay Castro, S., Thomson, S., Zorzoli, A., Meyer, B. H., Reglinski, M., Dorfmueller, H. C.. 2021-11-13. Recombinant Group A Carbohydrate backbone embedded into Outer Membrane Vesicles is a potent vaccine candidate targeting Group A Streptococcus from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis. https://doi.org/10.1101/2021.11.12.468441

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Microbially conjugated bile acids differentially affect the lifecycle and pathogenesis of Clostridioides difficile

Clostridioides difficile is a Gram-positive bacterium that causes C. difficile infection (CDI). In healthy adults, it has been proposed that the gut microbiota provides colonization resistance against C. difficile by competition through nutrient limitation and antagonism through secondary bile acid metabolism, the latter of which is mediated by the deconjugation of host-derived bile acids with bacterial bile salt hydrolases (BSH). Recently, BSHs have also shown an ability to reconjugate non-canonical (i.e., not glycine or taurine) amino acids to sterol cores, resulting in novel microbially conjugated bile acids (MCBAs). MCBAs have been associated with the resolution of recurrent CDI, though the mechanism underlying these effects are not well understood. To address this gap, we synthesized 36 MCBAs with nine amino acids (cysteine, isoleucine, leucine, phenylalanine, proline, serine, tryptophan, tyrosine, and valine) conjugated to the primary and secondary bile acids found in the human gut (CA, DCA, CDCA, and LCA) and tested their impact on various stages of C. difficiles lifecycle including bacterial outgrowth, membrane integrity, sporulation, and toxin activity. We show that BSH-mediated amidation of bile acid sterol cores can either increase or decrease inhibitory effects on C. difficile in an amino acid-dependent manner. For example, serine MCBAs enhanced C. difficiles ability to grow in otherwise inhibitory bile acid concentrations, increased spore production, and elevated toxin activity. Tryptophan MCBAs increased inhibition. By demonstrating these variable effects, our work clarifies the molecular determinants of MCBA activity and highlights specific MCBAs as promising targets for the development of C. difficile microbial-based therapeutics.

microbiology↗
bioRxiv2026

Magnetic organelle gene clusters enable bacterial growth and ATP homeostasis under oxidizing conditions

Biological organisms can produce magnetic nanoparticles made of magnetite to detect the Earth's magnetic field for orientation. The evolutionary mechanisms that led to the acquisition of this capacity remain unknown. The most ancient organisms known to perform magnetic orientation are magnetotactic bacteria. Under tight genetic control, they produce chains of magnetite nanoparticles in dedicated organelles to allow efficient navigation in aquatic environments containing molecular oxygen. Yet, these bacteria have been proposed to emerge before molecular oxygen became abundant on Earth, at a time when this navigation system could not have served its current function. Here, we show that gene clusters responsible of magnetite formation and organization enable resistance against hydrogen peroxide, a toxic oxygen-derived compound that was produced during the early stages of Earth's oxygenation when iron oxidation consumed molecular oxygen. Characterization of the nanoparticle's oxidation state supported the involvement of magnetite in resistance to hydrogen peroxide-induced oxidative stress. These findings are compatible with an early emergence of magnetotactic bacteria, before natural waters became oxygenated. We propose a conceptual framework to explain the origin of magnetic orientation in bacteria, and offer tools to identify the initiation of Earth's oxygenation in a time-resolved manner.

microbiology↗
bioRxiv2026

Identification and characterization of new P. aeruginosa phages using a surface receptor platform

Bacteriophages are of increasing interest for their potential use as alternatives to antibiotics for treating drug-resistant infections. Phage steering, specifically receptor-based steering, involves use of phages that bias the development of resistance in bacteria towards phenotypes such as reduced fitness. Phage therapy typically involves administering cocktails of phages with different targets to reduce the likelihood of resistance emerging. To ensure effective steering and cocktail design, there is a need to identify the receptors used by phages of interest, and to isolate phages that use diverse receptors. Here we describe a SURFAce Receptor (SURFAR) platform consisting of a set of defined Pseudomonas aeruginosa strains and mutants for rapid characterization of phage receptors. This platform can also be used to enrich for and isolate diverse phages from environmental samples, yielding novel phage genomes from wastewater. Using the SURFAR platform, two new phages were isolated and characterized: Dalewood, which targets both flagella and the conserved LPS outer core, and Bowman, a biofilm targeting phage capable of supressing growth of a subset of carbapenem-resistant clinical isolates. This tool helps to standardize the laborious but important task of phage receptor characterization, with the goal of expanding the known repertoire of P. aeruginosa phage receptors and phages.

microbiology↗