Biology subjects

Archer-Hartmann, S. A.

Publications and source records attributed to Archer-Hartmann, S. A..

5 recordsLinked to original sources

bioRxiv2026

Autoantibodies from recovered Guillain-Barre syndrome patients exhibit altered effector functions that prevent subsequent neuron degeneration

Guillain-Barre syndrome (GBS) is an autoimmune polyneuropathy that is the leading cause of nonpoliovirus-associated acute flaccid paralysis worldwide. In most cases, GBS occurs following an infection, most commonly Campylobacter jejuni, through the induction of antibodies recognizing bacterial ganglioside-mimicking lipooligosaccharides that cross-react with human neuronal gangliosides. This post-infectious autoimmune cascade causes neuropathy, from which patients can recover as their anti-ganglioside antibody titers diminish and immunostimulation decreases. In this study, we find 10% of clinically confirmed GBS patients maintain high titers of circulating anti-ganglioside antibodies more than one decade after recovery. These antibodies no longer cause neuropathy compared to acute sera from the same patients using a human pluripotent stem cell-derived sensory neuron model with human complement. We found both IgG subclass and glycoform differences between paired acute and recovered GBS patient sera, including anti-inflammatory modifications on isolated anti-GM1 ganglioside antibodies. Together, these data suggest that patients with GBS select for non-pathogenic variants of autoantibodies that are no longer capable of damaging their neurons, but may still protect against C. jejuni infection.

immunology↗

bioRxiv2024

The role of pigments in light color variation of the firefly Photinus pyralis

Fireflies use bioluminescent signals to communicate with their mates. Luciferase has been thought to be the sole contributor to light color; however, populations of the Photinus pyralis firefly display variation in the color of their emitted signals yet have identical luciferase sequences. Here, we examined whether pigments could be present in the light organs of the twilight-active species P. pyralis and contribute to this variation. We detected patterns of expression that suggest ommochrome and pterin screening pigments are expressed in P. pyralis light organs and could filter light emitted by luciferase and play a role in signal tuning. There were no significant differences between the pigment gene expression of P. pyralis individuals with yellower and greener signals. Our study provides alternative mechanisms that could influence pigments in P. pyralis light organs that could also play a role in modifying signal color.

evolutionary biology↗

bioRxiv2022

Post-translational modification by the Pgf glycosylation machinery modulates Streptococcus mutans physiology and virulence

Streptococcus mutans is a keystone pathogen of dental caries, and the ability to form biofilms is essential for its pathogenicity. We identified a glycosylation machinery (Pgf) in S. mutans that post-translationally modifies two surface-associated adhesins, Cnm and WapA. The four pgf genes (pgfS, pgfM1, pgfE, and pgfM2) are part of S. mutans core genome and we hypothesized that the scope of Pgf goes beyond Cnm and WapA. By inactivating each pgf gene individually or creating a quadruple pgf mutant in S. mutans OMZ175, we showed that the Pgf machinery is important for biofilm formation. Compared to OMZ175, differences in surface charge, membrane stability, and genetic competence were also observed for most mutants. Importantly, in silico analyses and tunicamycin MIC assays suggest a functional redundancy between the Pgf machinery and the rhamnose-glucose polysaccharide synthesis pathway. Using a rat oral colonization model, we showed a 10-fold reduction in recovered CFUs for the pgf quadruple mutant compared to OMZ175. Finally, using Cnm as a model, we showed by glycoproteomics analyses that Cnm is heavily modified with N-acetyl hexosamine in OMZ175 whereas phosphorylations were observed for the pgfS mutant. Our findings indicate that the Pgf machinery participates in important aspects of S. mutans pathobiology. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=164 SRC="FIGDIR/small/511621v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@146f37eorg.highwire.dtl.DTLVardef@11c0e45org.highwire.dtl.DTLVardef@ece1eaorg.highwire.dtl.DTLVardef@1e3f221_HPS_FORMAT_FIGEXP M_FIG C_FIG Abbreviated summaryIn this study, we demonstrate that the Pgf glycosylation machinery of Streptococcus mutans, a keystone pathogen of dental caries, regulates several aspects of bacterial pathophysiology that ultimately contribute to S. mutans fitness in oral colonization experiments. Using the heavily glycosylated Cnm adhesin as a model, we found that inactivation of the glycosyltransferase PgfS results in loss of Cnm glycosylation, but instead, Cnm became heavily phosphorylated, suggesting a crosstalk/competition between these two post-translational modification mechanisms.

microbiology↗

bioRxiv2020

Structure of the Xylan O-Acetyltransferase AtXOAT1 Reveals Molecular Insight into Polysaccharide Acetylation in Plants

Acetylation of biomolecules is gaining increased attention due to both the abundance and importance of this modification across all kingdoms of life. Xylans are a major component of plant cell walls and are the third most abundant biopolymer in Nature. O-Acetyl moieties are the dominant backbone substituents of glucuronoxylan in dicots and play a major role in the polymer-polymer interactions that are crucial for proper wall architecture and normal plant development. Here, we describe the biochemical, structural, and mechanistic characterization of Arabidopsis thaliana xylan O-acetyltransferase 1 (AtXOAT1), a member of the plant-specific Trichome Birefrigence Like (TBL) family that catalyzes the 2-O-acetylation of xylan. A multipronged approach involving X-ray crystallography, biochemical analyses, mutagenesis, and molecular simulations show that XOAT1 catalyzes xylan acetylation through formation of an acyl-enzyme intermediate by a double displacement bi-bi mechanism involving a Ser-His-Asp catalytic triad and unconventionally employs an arginine residue in formation of an oxyanion hole.

biochemistry↗

bioRxiv2018

Determining the link between alpha-gal-containing antigens in North American ticks and red meat allergy

Development of specific IgE antibodies to the oligosaccharide galactose--1, 3-galactose (-gal) following tick bites has been shown to be the source of red meat allergy. In this study, we investigated the presence of -gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteome, carbohydrate analysis, and basophil activation approaches. Using anti--gal antibodies, -gal was identified in the salivary glands of both Am. americanum and Ix. scapularis, while Am. maculatum and De. variabilis appeared to lack the sugar. PNGase F treatment confirmed the deglycosylation of N-linked -gal-containing proteins in tick salivary glands. Immunolocalization of -gal moieties to the salivary secretory vesicles of the salivary acini also confirmed the secretory nature of -gal-containing antigens in ticks. Am. americanum ticks were fed human blood (lacks -gal) using an artificial membrane feeding system to determine the source of -gal. N-linked glycan analysis revealed that Am. americanum and Ix. scapularis have -gal in their saliva and salivary glands, but Am. maculatum contains no detectable quantity. Salivary samples from Am. americanum and Ix. scapularis stimulated activation of basophils primed with plasma from -gal allergic subjects. Together, our data support the idea that bites from certain tick species may specifically create a risk for the development of -gal-specific IgE and hypersensitivity reactions in humans. Alpha-Gal syndrome challenges the current food allergy paradigm and broadens opportunities for future research.

immunology↗