Biology subjects

Coates, A. R.

Publications and source records attributed to Coates, A. R..

2 recordsLinked to original sources

bioRxiv2020

Antimicrobial activity of the quinoline derivative HT61, effective against non-dividing cells, in Staphylococcus aureus biofilms

Staphylococcus aureus is an opportunistic pathogen responsible for a wide range of chronic infections. Disease chronicity is often associated with biofilm formation, a phenotype that confers enhanced tolerance towards antimicrobials, a trait which can be attributed to a dormant, non-dividing subpopulation within the biofilm. Development of antibiofilm agents that target these populations could therefore improve treatment success. HT61 is a quinoline derivative that has demonstrated efficacy towards non-dividing planktonic Staphylococcus spp. and therefore, in principal, could be effective against staphylococcal biofilms. In this study HT61 was tested on mature S. aureus biofilms, assessing both antimicrobial efficacy and characterising the cellular response to treatment. HT61 was found to be more effective than vancomycin in killing S. aureus biofilms (minimum bactericidal concentrations: HT61; 32 mg/L, vancomycin; 64 mg/L), and in reducing biofilm biomass. Scanning electron microscopy of HT61-treated biofilms also revealed disrupted cellular structure and biofilm architecture. HT61 treatment resulted in increased expression of proteins associated with the cell wall stress stimulon and dcw cluster, implying global changes in peptidoglycan and cell wall biosynthesis. Altered expression of metabolic and translational proteins following treatment also confirm a general adaptive response. These findings suggest that HT61 represents a new treatment for S. aureus biofilm-associated infections that are otherwise tolerant to conventional antibiotics targeting actively dividing cells.

microbiology↗

bioRxiv2018

Increased rates of genomic mutation in a biofilm co-culture model of P. aeruginosa and S. aureus

Biofilms are major contributors to disease chronicity and are typically multi-species in nature. Pseudomonas aeruginosa and Staphylococcus aureus are leading causes of morbidity and mortality in a variety of chronic diseases but current in vitro dual-species biofilms models involving these pathogens are limited by short co-culture times (24 to 48 hours). Here, we describe the establishment of a stable (240 hour) co-culture biofilm model of P. aeruginosa and S. aureus that is reproducible and more representative of chronic disease.\n\nThe ability of two P. aeruginosa strains, (PAO1 and a cystic fibrosis isolate, PA21), to form co-culture biofilms with S. aureus was investigated. Co-culture was stable for longer periods using P. aeruginosa PA21 and S. aureus viability within the model improved in the presence of exogenous hemin. Biofilm co-culture was associated with increased tolerance of P. aeruginosa to tobramycin and increased susceptibility of S. aureus to tobramycin and a novel antimicrobial, HT61, previously shown to be more effective against non-dividing cultures of Staphylococcal spp. Biofilm growth was also associated with increased short-term mutation rates; 10-fold for P. aeruginosa and 500-fold for S. aureus.\n\nBy describing a reproducible 240 hour co-culture biofilm model of P. aeruginosa and S. aureus, we have shown that interspecies interactions between these organisms may influence short-term mutation rates and evolution, which could be of importance in understanding the adaptive processes that lead to the development of antimicrobial resistance.

microbiology↗