Biology subjects

Walsh, T. J.

Publications and source records attributed to Walsh, T. J..

3 recordsLinked to original sources

bioRxiv2024

Bacteriophage Treatment against Carbapenem-resistant Klebsiella pneumoniae (KPC) in a Neutropenic Murine Model of Gastrointestinal Translocation and Renal Infection

BackgroundCarbapenemase producing Klebsiella pneumoniae (KPC) are globally emerging pathogens which that cause life-threatening infections. Novel treatment alternatives are urgently needed. MethodsWe therefore investigated the effectiveness of three novel bacteriophages (Spivey, Pharr and Soft) in a neutropenic murine model of KPC gastrointestinal colonization, translocation, and disseminated infection. Bacteriophage efficacy was determined by residual bacterial burden of KPC in kidneys. Parallel studies were conducted of bacteriophage pharmacokinetics and resistance.. ResultsTreatment of mice with 5x109 PFU of phage cocktail via intraperitoneal injection was effective in significantly reducing renal KPC burden by 102 CFU (p<0.01) when administered every 24 hours and 103 CFU (p<0.01) every 12 hours. Moreover, a combination of bacteriophage and ceftazidime-avibactam produced a synergistic effect, resulting in a 105 reduction in bacterial burden in caecum and kidney (p<0.001 in both tissues). Prophylactic administration of bacteriophages via oral gavage did not prevent KPC translocation to the kidneys. Bacteriophage decay determined by linear regression of the ln of mean concentrations demonstrated R2 values in plasma of 0.941, kidney 0.976, and caecum 0.918, with half-lives of 2.5h < t1/2 < 3.5 h. Furthermore, a phage-resistant mutant displayed increased sensitivity to serum killing in vitro, but did not show significant defects in renal infection in vivo. ConclusionsA combination of bacteriophages demonstrated significant efficacy alone and synergy with ceftazidime/avibactam in treatment of experimental disseminated KPC infection in neutropenic mice.

microbiology↗

bioRxiv2024

Open-Channel Droplet Microfluidic Platform for Passive Generation of Human Sperm Microdroplets

Sperm cryopreservation is important for many individuals across the globe. Recent studies show that vitrification is a valuable approach for maintaining sperm quality after freeze-thawing processes and requires sub-microliter to microliter volumes. A major challenge for the adoption of vitrification in fertility laboratories is the ability to pipette small volumes of sample. Here, we present an open droplet generator that leverages open-channel microfluidics to passively generate sub-microliter to microliter volumes of purified human sperm samples and preserves sperm kinematics. We conclude that our platform is compatible with human sperm, an important foundation for future implementation of vitrification in fertility laboratories. Table of contents artwork O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/593416v3_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@1733ae0org.highwire.dtl.DTLVardef@1e638aorg.highwire.dtl.DTLVardef@119097forg.highwire.dtl.DTLVardef@be86f3_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2022

Ultraviolet Rate Constants of Pathogenic Bacteria: A Database of Genomic Modeling Predictions

A database of bacterial ultraviolet (UV) susceptibilities is developed from an empirical model that correlates genomic parameters with UV rate constants. Software is used to count and evaluate potential ultraviolet photodimers and identifying hot spots in bacterial genomes. The method counts dimers that potentially form between adjacent bases that occur at specific genomic motifs such as TT, TC, CT, & CC. Hot spots are identified where clusters of three or more consecutive pyrimidines can enhance absorption of UV photons. The model incorporates nine genomic parameters into a single variable for each species that represents its relative dimerization potential. The bacteria model is based on a curve fit of the dimerization potential to the ultraviolet rate constant data for 92 bacteria species represented by 216 data sets from published studies. There were 4 outliers excluded from the model resulting in a 98% Confidence Interval. The curve fit resulted in a Pearson correlation coefficient of 80%. All identifiable bacteria important to human health, including zoonotic bacteria, were included in the database and predictions of ultraviolet rate constants were made based on their specific genomes. This database is provided to assist healthcare personnel and researchers in the event of outbreaks of bacteria for which the ultraviolet susceptibility is untested and where it may be hazardous to assess due to virulence. Rapid sequencing of the complete genome of any emerging pathogen will now allow its ultraviolet susceptibility to be estimated with equal rapidity. Researchers are invited to challenge these predictions. ImportanceThis research demonstrates the feasibility of using the complete genomes of bacteria to determine their susceptibility to ultraviolet light. Ultraviolet rate constants can now be estimated in advance of any laboratory test. The genomic methods developed herein allow for the assembly of a complete database of ultraviolet susceptibilities of pathogenic bacteria without resorting to laboratory tests. This UV rate constant information can be used to size effective ultraviolet disinfection systems for any specific bacterial pathogen when it becomes a problem.

genomics↗