Publications by authors named "Tasia J Lightly"

As the demand for bacteriophage (phage) therapy increases due to antibiotic resistance in microbial pathogens, strategies and methods for increased efficiency, large-scale phage production need to be determined. To date, very little has been published on how to establish scalable production for phages, while achieving and maintaining a high titer in an economical manner. The present work outlines a phage production strategy using an enterotoxigenic Escherichia coli-targeting phage, 'Phage75', and accounts for the following variables: infection load, multiplicity of infection, temperature, media composition, harvest time, and host bacteria.

View Article and Find Full Text PDF

Background: Biofilm formation is a major clinical challenge contributing to treatment failure of periprosthetic joint infection (PJI). Lytic bacteriophages (phages) can target biofilm associated bacteria at localized sites of infection. The aim of this study is to investigate whether combination therapy of phage and vancomycin is capable of clearing biofilm-like aggregates formed in human synovial fluid.

View Article and Find Full Text PDF
Article Synopsis
  • Acinetobacter baumannii is a highly resistant pathogen causing challenging infections, leveraging a “persist and resist” strategy to survive harsh environments.
  • A specific operon involved in degrading phenylacetic acid (PAA) plays a crucial role in how this bacterium responds to antibiotics and can influence its virulence and resistance.
  • Disruption of PAA degradation increases A. baumannii's susceptibility to antibiotics and reduces its ability to cause infections, suggesting that targeting this pathway could lead to new treatments.
View Article and Find Full Text PDF

During phenylalanine catabolism, phenylacetic acid (PAA) is converted to phenylacetyl coenzyme A (PAA-CoA) by a ligase, PaaK, and then PAA-CoA is epoxidized by a multicomponent monooxygenase, PaaABCDE, before further degradation through the tricarboxylic acid (TCA) cycle. In the opportunistic pathogen , loss of attenuates virulence factor expression, which is under the control of the LuxIR-like quorum sensing (QS) system, CepIR. To further investigate the link between CepIR-regulated virulence and PAA catabolism, we created knockout mutants of the first step of the pathway (PAA-CoA synthesis by PaaK) and characterized them in comparison to a mutant using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and virulence assays.

View Article and Find Full Text PDF

Genetic tools are critical to dissecting the mechanisms governing cellular processes, from fundamental physiology to pathogenesis. Members of the genus have potential for biotechnological applications but can also cause disease in humans with a debilitated immune system. The lack of suitable genetic tools to edit GC-rich genomes has hampered the exploration of useful capacities and the understanding of pathogenic features.

View Article and Find Full Text PDF

Phenylacetic acid (PAA), an intermediate of phenylalanine degradation, is emerging as a signal molecule in microbial interactions with the host. In this work, we explore the presence of phenylalanine and PAA catabolism in 3 microbial pathogens of the cystic fibrosis (CF) lung microbiome: Pseudomonas aeruginosa, Burkholderia cenocepacia, and Aspergillus fumigatus. While in silico analysis of B.

View Article and Find Full Text PDF
Article Synopsis
  • The phenylacetic acid degradation pathway in Burkholderia cenocepacia is crucial for its full pathogenicity, especially in models mimicking cystic fibrosis, although the exact reasons are still unclear.
  • A specific mutant (ΔpaaABCDE), which cannot metabolize phenylacetic acid, was found to have decreased virulence due to quorum sensing inhibition, as it released phenylacetic acid into the environment.
  • This release hinders the bacterial communication system (quorum sensing) by reducing signaling molecules, suggesting that effective degradation of phenylacetic acid by wild-type B. cenocepacia helps maintain its pathogenic capabilities by preventing the buildup of compounds that inhibit this communication.
View Article and Find Full Text PDF