Animal Models for Drug Development for MRSA.

Animal Models for Drug Development for MRSA. Methods Mol Biol. 2020;2069:253-266 Authors: Marra A Abstract One of the foremost challenges of drug discovery in any therapeutic area is that of solidifying the correlation between in vitro activity and clinical efficacy. Between these is the confirmation that affecting a particular target in vivo will lead to a therapeutic benefit. In antibacterial drug discovery, there is a key advantage from the start, since the targets are bacteria-therefore, it is simple to ascertain in vitro whether a drug has the desired effect, i.e., bacterial cell inhibition or killing, and to understand the mechanism by which that occurs. The downstream criteria, whether a compound reaches the infection site and achieves appropriately high levels to affect bacterial viability, can be evaluated in animal models of infection. In this way animal models of infection can be a highly valuable and predictive bridge between in vitro drug discovery and early clinical evaluation.The Gram-positive pathogen Staphylococcus aureus causes a wide variety of infections in humans (Archer, Clin Infect Dis 26:1179-1181, 1998), and has been said to be able to infect every tissue type. Fortunately, over the years a great deal of effort has been expended toward developing infection models in rodents using this organism, with good success. This chapter describes the advantages, setups, and outcome measurements of the rodent models most used in drug discove...
Source: Mol Biol Cell - Category: Molecular Biology Authors: Tags: Methods Mol Biol Source Type: research

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Contributor : Akanksha RajputSeries Type : Expression profiling by high throughput sequencingOrganism : Staphylococcus aureusVancomycin Intermediate Staphylococcus aureus (VISA) strain originated during the prolonged hospitalization, chronic infection and vancomycin treatment. The hospital acquired D712 VISA strain were subjected to various sub-inhibitory concentration of nafcillin in Cation Adjusted Mueller Hinton Broth (CA-MHB) and Roswell Park Memorial Institute (RPMI) medium. The MIC of has dropped from 256 ug/ml to 1ug/ml in CA-MHB and RPMI media respectively. The cells were harvested and expression profiling were mea...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Staphylococcus aureus Source Type: research
Journal of Agricultural and Food ChemistryDOI: 10.1021/acs.jafc.9b06364
Source: Journal of Agricultural and Food Chemistry - Category: Food Science Authors: Source Type: research
Background: In US cystic fibrosis (CF) patients, methicillin-resistant Staphylococcus aureus (MRSA) rates have tripled in the past 2 decades. Known clinical risk factors include exposure to a healthcare setting, Pseudomonas aeruginosa and CF-related diabetes. Area-level socio-environmental exposures have not been evaluated. We explored the association of area-level deprivation with MRSA prevalence in a pediatric CF Center in the Southeastern United States. Methods: Patients’ residential addresses were geocoded and linked to a composite Area Deprivation Index and Rural-Urban Commuting Area scores. The association...
Source: The Pediatric Infectious Disease Journal - Category: Infectious Diseases Tags: Original Studies Source Type: research
Publication date: December 2019Source: Phytochemistry Letters, Volume 34Author(s): Shi-Ting Wang, Wen-Qi Qian, Peng He, Mei-Qing Feng, Yun Kang, Ya-Qin Wang, Jian-Ming HuangAbstractTwo new glycoalkaloids, manshurienine C (1) and 8-oxotetrahy-corydalmine-1-O-β-D-glucopyranoside (2), along with eleven known alkaloids (3–13), were isolated from the tubers of Stephania succifera. Their structures were elucidated by spectroscopic methods, including NMR and MS spectra. Compounds 5, 6, 8, and 10 showed in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA).Graphical abstract
Source: Phytochemistry Letters - Category: Chemistry Source Type: research
Conclusions: Oridonin antibacterial mechanism was related to changes in cell membrane and cell wall permeability, disturbance in protein and DNA metabolism, and influence on bacterial morphology. Thus, oridonin may help in treating MRSA infection. PMID: 31622118 [PubMed - in process]
Source: Pharmaceutical Biology - Category: Drugs & Pharmacology Tags: Pharm Biol Source Type: research
Authors: Bassetti M, Carnelutti A, Castaldo N, Peghin M Abstract Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) infections represent a leading cause of infection-related morbidity and mortality worldwide. There has been a welcome increase in the number of agents available for the treatment of MRSA infection over the last decade and several clinical trials are currently investigating the role of new experimental strategies. Areas covered: The purpose of this manuscript is to review the efficacy and safety of recently approved anti-MRSA molecules as well as some newer agents currently under investig...
Source: Expert Opinion on Pharmacotherapy - Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research
Authors: Yu H, Wang Y, Wang X, Guo J, Wang H, Zhang H, Du F Abstract Bacterial resistance to antimicrobial agents, including multidrug resistance, is an increasing problem in the treatment of infectious diseases. The development of resistance-modifying agents represents a potential strategy to alleviate the spread of bacterial resistance to antibiotics. A checkerboard microdilution assay was used to determine the synergy of jatrorrhizine and the antibiotic, norfloxacin (NFX). A bacterial ethidium bromide efflux assay, reverse transcription semi-quantitative polymerase chain reaction analysis and molecular docking s...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
Publication date: January 2020Source: Materials Science and Engineering: C, Volume 106Author(s): Ling-Yuan Guo, Shu-Zhen Yan, Xin Tao, Qing Yang, Qiang Li, Tian-Shu Wang, Shu-Qin Yu, Shuang-Lin ChenAbstractThere is an urgent need for new antibacterial strategies to overcome the emergence of antibiotic resistance. Antibacterial photodynamic therapy (APDT) may be an effective method to deliver photosensitizers for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we report that the photosensitizer hypocrellin A (HA) loaded into lipase-sensitive methoxy poly (ethylene glycol)-block-poly(&ep...
Source: Materials Science and Engineering: C - Category: Materials Science Source Type: research
In this study, we show that the Staphylococcus aureus COL (MRSA) strain, with a known complete genome, can easily survive and grow under acidic and alkaline conditions (pH5 and pH9, respectively), both planktonically and as a biofilm. A microarray-based analysis of both planktonic and biofilm cells was performed under acidic and alkaline conditions showing that several genes are up- or down-regulated under different environmental conditions and growth modes. These genes were coding for transcription regulators, ion transporters, cell wall biosynthetic enzymes, autolytic enzymes, adhesion proteins and antibiotic resistance ...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
In this study, we investigated the prevalence of the tst gene in clinical isolates of S. aureus. Then, animal experiments were performed to further evaluate the influence of the presence of the tst gene associated Staphylococcus aureus Pathogenicity Island (SaPI) on body weight, serum cytokine concentrations and the bacterial load in different organs. In addition, macrophages were used to analyze the secretion of cytokines in vitro and bacterial survival in the cytoplasm. Finally, pathological analysis was carried out to evaluate organ tissue impairment. The results demonstrated that the prevalence of tst gene was approxim...
Source: Microbial Pathogenesis - Category: Infectious Diseases Source Type: research
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