Biology subjects

Harris, J. S.

Publications and source records attributed to Harris, J. S..

4 recordsLinked to original sources

bioRxiv2026

Human Saliva Induces Acetoin-Dependent Metabolic Adaptation that Promotes Stress Tolerance in Streptococcus mutans

Oral microbes are continually exposed to host-derived saliva, yet its effects on bacterial metabolism and stress adaptation remain incompletely defined. We investigated how saliva supplementation alters the physiology of the caries-associated bacterium Streptococcus mutans using transcriptomics (RNA-Seq), targeted metabolite measurements, specific gene deletions, and transposon sequencing (Tn-Seq). Growth in a chemically defined medium supplemented with pooled saliva altered expression of genes involved in carbohydrate transport, purine biosynthesis, and pyruvate-associated metabolism, including induction of the acetoin dehydrogenase operon. Saliva significantly increased extracellular acetoin accumulation across all S. mutans isolates tested, whereas little accumulation occurred in two commensal streptococcal species examined. Deletion of acetolactate synthase/decarboxylase (alsSaldB) abolished the saliva-associated increase, while deletion of individual acetoin dehydrogenase components (adhC / lplA) enhanced accumulation, supporting the predicted roles of genes in acetoin synthesis and catabolism. Increasing the available carbohydrate concentrations within the media further increased acetoin accumulation, alongside declining terminal culture pH that was significantly lower in cultures supplemented with saliva. Following growth with saliva, S. mutans exhibited approximately 10,000-fold greater survival during a hydrogen peroxide challenge than cells grown without saliva. Mutants within the acetoin pathway retained saliva-associated protection but showed approximately 100-fold lower survival than the wild type. Serial passage of a pooled transposon library identified previously unrecognized saliva-associated fitness determinants, including depletion of mutants carrying insertions in the acetoin dehydrogenase operon. Together, these findings identify acetoin metabolism as a contributor to saliva-associated metabolic remodeling and oxidative stress tolerance in S. mutans and establish saliva as a critical modulator of S. mutans physiology.

microbiology↗

bioRxiv2020

Vertical-junction Photodiodes for High-resolution Retinal Prostheses

ObjectiveTo restore central vision in patients with atrophic age-related macular degeneration, we replace the lost photoreceptors with photovoltaic pixels, which convert light into current and stimulate the secondary retinal neurons. Clinical trials demonstrated prosthetic acuity closely matching the sampling limit of the 100 m pixels, and hence smaller pixels are required for improving visual acuity. However, with smaller flat bipolar pixels, the electric field penetration depth and the photodiode responsivity significantly decrease, making the device inefficient. Smaller pixels may be enabled (1) by increasing the diode responsivity using vertical p-n junctions and (2) by directing the electric field vertically using 3-D electrodes. Here, we demonstrate such novel photodiodes and test the retinal stimulation in a vertical electric field. ApproachArrays of silicon photodiodes of 55, 40, 30, and 20 m in width, with vertical p-n junctions, were fabricated. The electric field in the retina was directed vertically by a common return electrode at the edge of the devices. Optical and electronic performance of the diodes was characterized in-vitro, and retinal stimulation threshold measured by recording the visually evoked potentials (VEPs) in rats with retinal degeneration. Main resultsThe photodiodes exhibited sufficiently low dark current (<10 pA) and responsivity at 880 nm wavelength as high as 0.51 A/W, with 85% internal quantum efficiency, independent of pixel size. Field mapping in saline demonstrated uniformity of the pixel performance in the array. The full-field stimulation threshold was as low as 0.057{+/-}0.029 mW/mm2 with 10 ms pulses, independent of pixel size. SignificancePhotodiodes with vertical p-n junctions demonstrated excellent charge collection efficiency independent of pixel size, down to 20 m. Vertically-oriented electric field provides a stimulation threshold that is independent of pixel size. These results are the first steps in validation of the feasibility of scaling down the photovoltaic pixels for subretinal stimulation.

bioengineering↗

bioRxiv2020

The Species-specific Acquisition and Diversification of a Novel Family of Killer Toxins in Budding Yeasts of the Saccharomycotina.

Killer toxins are extracellular antifungal proteins that are produced by a wide variety of fungi, including Saccharomyces yeasts. Although many Saccharomyces killer toxins have been previously identified, their evolutionary origins remain uncertain given that many of the se genes have been mobilized by double-stranded RNA (dsRNA) viruses. A survey of yeasts from the Saccharomyces genus has identified a novel killer toxin with a unique spectrum of activity produced by Saccharomyces paradoxus. The expression of this novel killer toxin is associated with the presence of a dsRNA totivirus and a satellite dsRNA. Genetic sequencing of the satellite dsRNA confirmed that it encodes a killer toxin with homology to the canonical ionophoric K1 toxin from Saccharomyces cerevisiae and has been named K1-like (K1L). Genomic homologs of K1L were identified in six non-Saccharomyces yeast species of the Saccharomycotina subphylum, predominantly in subtelomeric regions of the yeast genome. The sporadic distribution of these genes supports their acquisition by horizontal gene transfer followed by diversification, with evidence of gene amplification and positive natural selection. When ectopically expressed in S. cerevisiae from cloned cDNAs, both K1L and its homologs can inhibit the growth of competing yeast species, confirming the discovery of a new family of biologically active killer toxins. The phylogenetic relationship between K1L and its homologs suggests gene flow via dsRNAs and DNAs across taxonomic divisions to enable the acquisition of a diverse arsenal of killer toxins for use in niche competition.

genetics↗

bioRxiv2018

The Pseudomonas aeruginosa Wsp pathway undergoes positive evolutionary selection during chronic infection

Author Contributions Author Contributions Introductory paragraph Results Discussion Materials and Methods References ESG and CWM performed the experimental work. JSH performed the colony PCR. SBC infected and sampled the porcine burn wounds. DS generated the sequence library. MW and GRL quantified the strain frequency in the wounds. ESG, CWM, MW, VSC, and DJW conceptualized the project and wrote the manuscript.\n\nIntroductory paragraph Author Contributions Introductory paragraph Results Discussion Materials and Methods References Pathogens experience pressure in an infection to adapt, with selection favoring mutants that persist. Pseudomonas aeruginosa commonly ad ...

microbiology↗