Transcriptional Analysis of the Effects of Gambogic Acid and Neogambogic Acid on Methicillin-Resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) infection is a major threat to human health, as this bacterium has developed resistance to a variety of conventional antibiotics. This is especially true of MRSA biofilms, which not only exhibit enhanced pathogenicity but also are resistant to most antibiotics. In this work, we demonstrated that two natural products with antitumor activity, namely, gambogic acid (GA) and neogambogic acid (NGA), have significant inhibitory activity toward MRSA. GA and NGA can not only effectively inhibit planktonic MRSA strains in vivo and in vitro, but also have strong inhibitory effects on MRSA biofilms formation. By transcriptome sequencing, Q-RT-PCR and PRM, we found that GA and NGA could reduce the expression of S. aureus virulence factors by inhibiting the saeRS two-component, thus achieving inhibition of MRSA. We found that GA and NGA had anti-MRSA activity in vivo and in vitro and identified saeRS to be the target, indicating that saeRS inhibitors may be used to treat biofilm-related infections.
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research

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Publication date: Available online 12 October 2019Source: Journal of Advanced ResearchAuthor(s): Yanguang Cong, Sijin Yang, Xiancai RaoAbstractThe infection caused by methicillin-resistant Staphylococcus aureus (MRSA) is a global threat to public health. Vancomycin remains one of the first-line drugs for the treatment of MRSA infections. However, S. aureus isolates with complete resistance to vancomycin have emerged in recent years. Vancomycin-resistant S. aureus (VRSA) is mediated by a vanA gene cluster, which is transferred from vancomycin-resistant enterococcus. Since the first VRSA isolate was recovered from Michigan, ...
Source: Journal of Advanced Research - Category: Research Source Type: research
Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), is an important human pathogen that exhibit enhanced virulence and resistance to different antibiotics. It causes a wide range of infections from mild to life-threatening conditions, both in the hospital (healthcare-associated-infections/HAIs) and in the community (community-associated-infections/CAIs), resulting in increased costs for the healthcare system [1,2]. Although there has been a recent decrease in HAIs (but not among CA invasive infections), caused by MRSA, in EEUU [3] and in some European countries [4], the attributable mortality due to...
Source: Journal of Infection - Category: Infectious Diseases Authors: Source Type: research
Authors: Bassetti M, Russo A, Carnelutti A, Wilcox M Abstract Introduction: In clinical practice, methicillin-resistant Staphylococcus aureus (MRSA) represents a major threat and has been associated with high rates of inadequate antibiotic treatment and significant increases in morbidity, mortality and overall healthcare costs. The association between the prescription of an inappropriate or delayed antibiotic and impaired clinical outcomes has been widely described. Areas covered: To address the threat of MRSA, many new therapeutic options with a peculiar activity against MRSA have been recently developed and appro...
Source: Expert Opinion on Emerging Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Emerg Drugs Source Type: research
The emergence of vancomycin-resistant Staphylococcus aureus (VRSA) has become a global concern for public health. The proximity of vancomycin-resistant enterococcus (VRE) and methicillin-resistant S. aureus (MRSA...
Source: Annals of Clinical Microbiology and Antimicrobials - Category: Microbiology Authors: Tags: Research Source Type: research
In this study, there was a high prevalence of the EMRSA-15 clone presenting multiple resistances in diabetic foot ulcers making these infections complicated to treat leading to a higher morbidity and mortality in diabetic patients.
Source: European Journal of Clinical Microbiology and Infectious Diseases - Category: Microbiology Source Type: research
Molecules, Vol. 24, Pages 3650: Synthesis, Docking Studies, and In Vitro Evaluation of Some Novel Thienopyridines and Fused Thienopyridine–Quinolines as Antibacterial Agents and DNA Gyrase Inhibitors Molecules doi: 10.3390/molecules24203650 Authors: Eman M. Mohi El-Deen Eman A. Abd El-Meguid Sherifa Hasabelnaby Eman A. Karam Eman S. Nossier A series of novel thienopyridines and pyridothienoquinolines (3a,b–14) was synthesized, starting with 2-thioxo-1,2-dihydropyridine-3-carbonitriles 1a and 1b. All compounds were evaluated for their in vitro antimicrobial activity against six bacterial stra...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
Planta Med DOI: 10.1055/a-1013-0434The development of multiple antibiotic–resistant bacteria has vastly depleted our repertoire of effective antibiotic chemotherapies. The development of multi-β-lactam-resistant strains are particularly concerning due to our previous reliance on this class of antibiotics because of their initial efficacy and broad-spectrum activity. With increases in extended-spectrum β-lactam-resistance and an expanded resistance to other classes of antibiotics, there is an urgent need for the development of effective new antibiotic therapies. Terminalia ferdinandiana is an endemic Austral...
Source: Planta Medica - Category: Drugs & Pharmacology Authors: Tags: Original Papers Source Type: research
Abstract Co-trimoxazole (SXT) is a combination therapeutic that consists of sulfamethoxazole and trimethoprim that is increasingly used to treat skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA). However, the use of SXT is limited to the treatment of low-burden, superficial S. aureus infections and its therapeutic value is compromised by the frequent emergence of resistance. As a first step towards the identification of approaches to enhance the efficacy of SXT, we examined the role of bacterial DNA repair in antibiotic susceptibility and mutagenesis. We found that mutant...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
In this study, we investigated the role and anti-infection mechanism of sublancin in a mouse model of MRSA-induced sublethal infection. Sublancin could modulate innate immunity by inducing the production of IL-1β, IL-6, TNF-α, and nitric oxide, enhancing phagocytosis and MRSA-killing activity in both RAW264.7 cells and mouse peritoneal macrophages. The enhanced macrophage function by the peptide in vitro correlated with stronger protective activity in vivo in the MRSA-invasive sublethal infection model. Macrophage activation by sublancin was found to be partly dependent on TLR4 and the NF-κB and MAPK signa...
Source: Journal of Immunology Research - Category: Allergy & Immunology Tags: J Immunol Res Source Type: research
ConclusionMRSA strain Lr12 has a novel sequence type (ST5352) and could be used as a reference strain for comparative genomic analysis of other MRSA strains belong to ST5352.
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
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