Biology subjects

Shouldice, A. C.

Publications and source records attributed to Shouldice, A. C..

3 recordsLinked to original sources

bioRxiv2025

The vaginal microbiota, symptoms, and local immune correlates in transmasculine individuals using sustained testosterone therapy

Transmasculine individuals (assigned female at birth, masculine gender identity, TM) may use gender-affirming testosterone therapy, and some TM report adverse genital symptoms during treatment. In cis women, the vaginal microbiota is a key determinant of reproductive and sexual health outcomes; Lactobacillus-dominant communities are considered optimal, while more even, diverse, Lactobacillus-depleted microbiota are considered non-optimal. Prior studies suggest Lactobacillus deficiency in TM vaginal microbiota, but associations with symptoms and immune markers remain unclear. We launched the TransBiota study to characterize the TM vaginal microbiota, soluble mediators of local inflammation (SMI), and self-reported symptoms over three weeks. Fewer than 10% of TM possessed Lactobacillus-dominant microbiota, and most exhibited more diverse, Lactobacillus-depleted microbiota. We identified 11 vaginal microbiota community state types (tmCSTs), with Lactobacillus-dominant tmCSTs unexpectedly linked to abnormal odor and elevated IL-1. These findings indicate that Lactobacillus dominance may no longer be an optimal state for TM during gender-affirming testosterone therapy and change in clinical management is needed.

microbiology↗

bioRxiv2025

The Neovaginal Microbiota, Symptoms, and Local Immune Correlates in Transfeminine Individuals with Penile Inversion Vaginoplasty

Transfeminine people (assigned male at birth) often undergo penile inversion vaginoplasty to create vulva, a clitoris and a vaginal canal (referred to as a neovagina). After vaginoplasty, transfeminine people frequently experience gynecological concerns but their etiology is unknown due to a lack of knowledge of the neovaginal microenvironment. We characterized neovaginal microbiota and cytokines in 47 transfeminine participants. Participants self-reported sexual behaviors and symptoms, enabling correlation with bacterial (16S rRNA) and immune profiles. Four distinct clusters of co-occurring bacteria with unique immune profiles were identified. One cluster, which included Fastidiosipila, Ezakiella, and Murdochiella, was abundant, stable, and correlated with lower cytokines. Conversely, another cluster containing Howardella, Parvimonas, Fusobacterium, and Lawsonella was linked to higher cytokines. Although Lactobacillus was detected, Lactobacillus-dominance was rare. These findings underscore the need for evidence-based clinical guidelines tailored to transfeminine gynecologic care, emphasizing the vital role of the neovaginal microbiome in symptom management and sexual health.

microbiology↗

bioRxiv2022

The Staphylococcus aureus iron-regulated surface determinant A (IsdA) increases SARS CoV-2 replication by modulating JAK-STAT signaling

The emergence and spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) and the associated Coronavirus disease (COVID-19) pandemic have affected millions globally. Like other respiratory viruses, a significant complication of COVID-19 infection is secondary bacterial co-infection, which is seen in approximately 25% of severe cases. The most common organism isolated from co-infection is the Gram-positive bacterium Staphylococcus aureus. Here, we developed an in vitro co-infection model where both CoV-2 and S. aureus replication kinetics can be examined. We demonstrate CoV-2 infection does not alter how S. aureus attaches to or grows in host epithelial cells. In contrast, the presence of replicating S. aureus enhances the replication of CoV-2 by 10-15-fold. We identify this pro-viral activity is due to the S. aureus iron-regulated surface determinant A (IsdA) and this effect is mimicked across different SARS CoV-2 permissive cell lines infected with multiple viral variants. Analysis of co-infected cells demonstrated an IsdA dependent modification of host transcription. Using chemical inhibition, we determined S. aureus IsdA modifies host Janus Kinase - Signal Transducer and Activator of Transcription (JAK-STAT) signalling, ultimately leading to increased viral replication. These findings provide key insight into the molecular interactions that occur between host cells, CoV-2 and S. aureus during co-infection. ImportanceBacterial co-infection is a common and significant complication of respiratory viral infection, including in patients with COVID-19, and leads to increased morbidity and mortality. The relationship between virus, bacteria and host is largely unknown, which makes it difficult to design effective treatment strategies. In the present study we created a model of co-infection between SARS CoV-2 and Staphylococcus aureus, the most common species identified in COVID-19 patients with co-infection. We demonstrate that the S. aureus protein IsdA enhances the replication of SARS CoV-2 in vitro by modulating host cell signal transduction pathways. The significance of this finding is in identifying a bacterial component that enhances CoV-2 pathogenesis, which could be a target for the development of co-infection specific therapy in the future. In addition, this protein can be used as a tool to decipher the mechanisms by which CoV-2 manipulates the host cell, providing a better understanding of COVID-19 virulence.

microbiology↗