Biology subjects

Burton, J. P.

Publications and source records attributed to Burton, J. P..

4 recordsLinked to original sources

bioRxiv2024

TSST-1 promotes colonization of Staphylococcus aureus within the vaginal tract by activation of CD8+T cells

Toxic shock syndrome toxin-1 (TSST-1) is a superantigen produced by Staphylococcus aureus and is the determinant of menstrual toxic shock syndrome (mTSS); however, the impact of TSST-1 on the vaginal environment beyond mTSS is not understood. Herein, we assessed how TSST-1 affects vaginal colonization by S. aureus, host inflammatory responses, and changes in microbial communities within the murine vagina. We demonstrated that TSST-1 induced a CD8+ T cell-dependent inflammatory response by 24 hours that correlated with an increased bacteria burden within the vaginal tract. This increase was due to superantigen-dependent T cell activation that triggered a change in microbial composition within the vaginal tract. Altogether, this study demonstrates that within the vaginal tract, TSST-1 modulates the vaginal microbiota to favor the survival of S. aureus in the absence of mTSS. ImportanceToxic shock syndrome toxin-1 (TSST-1) is a superantigen toxin produced from Staphylococcus aureus that causes the menstrual form of toxic shock syndrome. This research demonstrates that TSST-1 also has a wider function within the vaginal tract than previously expected. We show that TSST-1, by activating CD8+ T cells, induces an inflammatory environment that modifies the vaginal microbiota to favor colonization by S. aureus. These are important findings as S. aureus can colonize the human vaginal tract efficiently and subsequently trigger dysbiosis within the microbial communities leading to several adverse outcomes such as decreased fertility, increased risks for sexually transmitted diseases and issues related to pregnancy and birth.

microbiology↗

bioRxiv2022

Bacterial association with metals enables in vivo tracking of microbiota using magnetic resonance imaging

Bacteria constitute a significant part of the biomass of the human microbiota, but their interactions are complex and difficult to replicate outside the host. Exploiting the superior resolution of magnetic resonance imaging (MRI) to examine signal parameters of selected human isolates may allow tracking of their dispersion throughout the body. We investigated longitudinal and transverse MRI relaxation rates and found significant differences between several bacterial strains. Common commensal strains of lactobacilli display notably high MRI relaxation rates, partially explained by outstanding cellular manganese content, while other species contain more iron than manganese. Lactobacillus crispatus show particularly high values, 4-fold greater than any other species; over 10-fold greater signal than relevant tissue background; and a linear relationship between relaxation rate and fraction of live cells. Different bacterial strains have detectable, repeatable MRI relaxation rates that in future may enable tracking of their persistence in the human body for enhanced molecular imaging. IMPORTANCE To understand how spatial and temporal distribution of microbiota impact human health, dynamic tools for monitoring microbiota landscapes inside the host are needed. Particularly when considering the complexity of the gastrointestinal tract and the microbiota that dwell within, tools for monitoring deep segments of the gut non-invasively are required. Medical imaging provides solutions that enable the study of microorganisms in their preferred niche regardless of health status. To bootstrap this technology, we investigated the magnetic resonance imaging (MRI) properties of bacterial isolates and showed that outstanding signal detection is an inherent property of several strains. Among these, we showed that bacteria relying on manganese metabolism have an MRI characteristic that is distinct from mammalian cells. Our findings will lead to direct and safe imaging of bacteria; influence how we monitor both infection and gut health; and help direct the use of antibiotics to curtail the growing threat of antibiotic resistance.

microbiology↗

bioRxiv2019

Potential role of extracellular ATP released by bacteria in bladder infection and contractility

Urgency urinary incontinence (UUI), the result of conditions such as overactive bladder (OAB), could potentially be influenced by both commensal and urinary tract infection-associated bacteria. The sensing of bladder filling involves interplay between various parts of the nervous system eventually resulting in contraction of the detrusor muscle during micturition. Here we model host responses to various urogenital bacteria, firstly by using urothelial bladder cell lines and then with myofibroblast contraction assays. To measure responses, we examined calcium influx, gene expression and alpha smooth muscle actin deposition assays. We found that organisms such as Escherichia coli and Gardnerella vaginalis strongly induced calcium influx and contraction, whereas, Lactobacillus crispatus and L. gasseri did not induce this response. Additionally, supernatants from lactobacilli impeded influx-and contraction induced by the uropathogens. Upon further investigation of factors associated with the purinergic signaling pathways, we found that influx and contraction of cells correlated to the amount of extracellular ATP produced by E. coli. Certain lactobacilli appear to mitigate this response by utilizing extracellular ATP or producing inhibitory compounds which can act as a receptor agonist or calcium channel blocker. These findings suggest that members of the urinary microbiota may be influencing UUI.

microbiology↗

bioRxiv2019

The Impact of Uremia and Intestinal Dysbiosis on Hepatic Drug Metabolism in a Rat Model of Progressive Chronic Kidney Disease

Nonrenal clearance pathways such as drug metabolism are decreased in chronic kidney disease (CKD). Although the mechanism remains elusive, uremic toxin retention and an altered gut microbiota are suspected to influence cytochrome P450s (CYPs) contributing to the unpredictable pharmacokinetics in patients with CKD. We characterized dysbiosis and uremia in CKD to elucidate associations between CYP expression and CKD progression. Rats fed control or CKD-inducing adenine diet were subsequently studied at five time points over 42 days. CYP expression and activity were compared to alterations in the 1) plasma and liver metabolome and 2) gut bacterial microbiota. CYP3A2 and CYP2C11 were downregulated in CKD by [≥]76% (p<0.001) concurrently with or slightly prior to CKD onset as defined by serum creatinine. Metabolite profiles were altered prior to changes in the gut microbiota, and gut-derived uremic toxins including indoxyl sulfate, phenyl sulfate and 4-ethylphenyl sulfate correlated with CYP3A2 or CYP2C11 expression. Bacterial genera Turicibacter and Parabacteroides were identified as being characteristic of CKD. In conclusion, CYP3A2 and CYP2C11 are downregulated before dysbiosis and correlate with select uremic toxins.

pharmacology and toxicology↗