Project description:Bacteria commonly adapt to stresses by altering gene expression. To understand the response of M. tuberculosis (MTB) to various antibacterial agents, we performed transcriptomics on MTB bacilli exposed to several test compounds as well as known drugs (capreomycin, cycloserine, ethionamide, isoniazid, kanamycin, moxifloxacin, PA-824, rifampicin, streptomycin). Bacteria were exposed for 16 hrs to various concentrations of each drug (different multiples of the compound's MIC), as noted in the title of each sample. RNA was isolated and applied to arrays provided by TIGR under the NIAID contract N01-AI-15447
Project description:The antibacterial activity of novel 1,10-phenanthroline complexes of Cu(II), Mn(II) and Ag(I) against multidrug-resistant clinical isolates derived from Irish patients
Project description:Bacteria commonly adapt to stresses by altering gene expression. To understand the response of M. tuberculosis (MTB) to various antibacterial agents, we performed transcriptomics on MTB bacilli exposed to several test compounds as well as known drugs (capreomycin, cycloserine, ethionamide, isoniazid, kanamycin, moxifloxacin, PA-824, rifampicin, streptomycin).
Project description:Bovine respiratory disease complex (BRDC) is an important cause of mortality and morbidity in cattle; costing the dairy and beef industries millions of dollars annually, despite the use of vaccines and antibiotics. BRDC is caused by one or more of several viruses (bovine respiratory syncytial virus, bovine herpes type 1 also known as infectious bovine rhinotracheitis, and bovine viral diarrhea virus), which predispose animals to infection with one or more bacteria. These include: Pasteurella multocida, Mannheimia haemolytica, Mycoplasma bovis, and Histophilus somni. Some cattle appear to be more resistant to BRDC than others. We hypothesize that appropriate immune responses to these pathogens are subject to genetic control. To determine which genes are involved in the immune response to each of these pathogens it was first necessary to experimentally induce infection separately with each pathogen to document clinical and pathological responses in animals from which tissues were harvested for subsequent RNA sequencing. Herein these infections and animal responses are described.
Project description:Antibiotic overuse and mass production have led to a global problem with the treatment of antibacterial infections. Thus, any possibility to limit the number of antibacterial drugs used will contribute to a decrease in the development of pathogenic bacterial resistance. In this study, the enhanced bacterial growth reduction of pharmaceutical activated carbon (PAC) material with adsorbed antimicrobial agents compared to the activity of pure antibacterial drugs was investigated. Sulfamethoxazole (SMZ) at a concentration of 1.1 mg/mL retained the growth of S. aureus and E. coli at 20.5% and 26.5%, respectively, whereas SMZ adsorbed on PAC increased the reduction of the tested bacteria in the range of 47-72%. The use of PAC with adsorbed gentamycin (G) over 24 h improved the effectiveness of E. coli growth reduction by 50% compared to the application of pure antibiotic (3.6 µg/mL). The increased reduction of S. aureus growth by 6% using G with PAC for a 24-h incubation time compared to the use of pure antibiotics at a concentration of 3.6 µg/mL was observed. The results provide proof-of-principle that the new approach of activated carbon with adsorbed antimicrobial agents could yield an attractive background with potential as a new starting material for S. aureus and E. coli pathogen elimination, e.g., in wound-healing treatment in the future.
Project description:An anionic amphiphilic dendrimer is reported that possesses increased cytotoxicological potency against prokaryotic cells compared to eukaryotic cells. The half-maximal effective concentration (EC50) for the dendrimer against Bacillus subtilis, a Gram-positive bacterial strain, was measured to be 4.1 x 10(-5) M, while that against human umbilical vein endothelial cells (HUVEC) was more than 36x greater at a value of 1.5 x 10(-3) M. EC50 ratios for two commercial amphiphiles, sodium dodecyl sulfate (SDS) and Triton X-100, in addition to a similar synthesized dendritic structure were at most only 3.8x greater. Furthermore, the observed EC50 values appear to be correlated to the critical aggregation constant (CAC) in solution suggesting a mechanism of action for these anionic amphiphilic dendrimers related to their supramolecular structures.
Project description:Multi-drug resistance is a growing problem in the treatment of infectious diseases and the widespread use of broad-spectrum antibiotics has produced antibiotic resistance for many human bacterial pathogens. Advances in nanotechnology have opened new horizons in nanomedicine, allowing the synthesis of nanoparticles that can be assembled into complex architectures. Novel studies and technologies are devoted to understanding the mechanisms of disease for the design of new drugs, but unfortunately infectious diseases continue to be a major health burden worldwide. Since ancient times, silver was known for its anti-bacterial effects and for centuries it has been used for prevention and control of disparate infections. Currently nanotechnology and nanomaterials are fully integrated in common applications and objects that we use every day. In addition, the silver nanoparticles are attracting much interest because of their potent antibacterial activity. Many studies have also shown an important activity of silver nanoparticles against bacterial biofilms. This review aims to summarize the emerging efforts to address current challenges and solutions in the treatment of infectious diseases, particularly the use of nanosilver antimicrobials.
Project description:The number of antibacterial agents in clinical and preclinical development possessing activity against a narrow spectrum of bacterial pathogens is increasing, with many of them being nontraditional products. The key value proposition hinges on sparing antibiotic use and curtailing the emergence of resistance, as well as preventing the destruction of a beneficial microbiome, versus the immediate need for effective treatment of an active infection with a high risk of mortality. The clinical use of a targeted spectrum agent, most likely in combination with a rapid and robust diagnostic test, is a commendable goal with significant healthcare benefits if executed correctly. However, the path to achieving this will come with several challenges, and many scientific and clinical development disciplines will need to align their efforts to successfully change the treatment paradigm.
Project description:The antibacterial activity of a series of nitric oxide (NO)-releasing poly(propylene imine) (PPI) dendrimers was evaluated against both Gram-positive and Gram-negative pathogenic bacteria, including methicillin-resistant Staphylococcus aureus . A direct comparison of the bactericidal efficacy between NO-releasing and control PPI dendrimers (i.e., non-NO-releasing) revealed both enhanced biocidal action of NO-releasing dendrimers and reduced toxicity against mammalian fibroblast cells. Antibacterial activity for the NO donor-functionalized PPI dendrimers was shown to be a function of both dendrimer size (molecular weight) and exterior functionality. In addition to minimal toxicity against fibroblasts, NO-releasing PPI dendrimers modified with styrene oxide exhibited the greatest biocidal activity (≥99.999% killing) against all bacterial strains tested. The N-diazeniumdiolate NO donor-functionalized PPI dendrimers presented in this study hold promise as effective NO-based therapeutics for combating bacterial infections.