Isovalerylshikonin, a new resistance-modifying agent from Arnebia euchroma, supresses antibiotic resistance of drug-resistant Staphylococcus aureus.

08:00 EDT 31st August 2018 | BioPortfolio

Summary of "Isovalerylshikonin, a new resistance-modifying agent from Arnebia euchroma, supresses antibiotic resistance of drug-resistant Staphylococcus aureus."

Antimicrobial resistance is the greatest threat to the treatment of bacterial infectious diseases. The development of resistance-modifying agents represents a promising strategy to mitigate the spread of bacterial antibiotic resistance. A natural product, isovalerylshikonin (IVS), was isolated from traditional Chinese medicine Arnebia euchroma in this study, which exhibited marginal antibacterial activity against drug-resistant Staphylococcus aureus RN4220, with an MIC of 16 mg/L. In addition, a synergistic effect between IVS and streptomycin was detected by the microdilution antimicrobial checkerboard assay, with a reduction in the MIC of IVS by up to 32-fold against RN4220. A bacterial EtBr efflux assay and RT-PCR were performed to investigate the mechanism of the synergy. IVS significantly inhibited the bacterial efflux and expression of msrA mRNA in the in vitro experiment. A peritonitis/sepsis model was employed to test the in vivo synergistic activity of IVS and STM. IVS synergistically decreased the bacteria count with STM in peritoneal, spleen and liver, and increased mouse survival with STM in 7 days. The acute toxicity of IVS was tested, and the LD of IVS with a single exposure was 2.584 g/kg in mice. Overall, isovalerylshikonin, a low toxicity resistance-modifying agent, exhibited synergistic antibacterial activities in vitro and in vivo against drug-resistant S. aureus. The effects were mediated by suppression of msrA mRNA expression and bacterial efflux. In addition, these data support that IVS is a potential resistance-modifying agent against microbial resistance caused by msrA efflux pump.


Journal Details

This article was published in the following journal.

Name: International journal of antimicrobial agents
ISSN: 1872-7913


DeepDyve research library

PubMed Articles [8295 Associated PubMed Articles listed on BioPortfolio]

Meroterpenoids isolated from Arnebia euchroma (Royle) Johnst. And their cytotoxic activity in human hepatocellular carcinoma cells.

Six previously undescribed naturally occurring meroterpenoids (2, 5-9) together with seven known meroterpenoids (1, 3, 4, 10-13) were isolated from the root plant of Arnebia euchroma. Their structures...

Characterizations and immunostimulatory activities of a polysaccharide from Arnebia euchroma (Royle) Johnst. roots.

A polysaccharide from Arnebia euchroma (Royle) Johnst. named ARP, was obtained and purified by the hot water extraction, ethanol precipitation and deproteinization of TCA. The molecular weight of the ...

Identification of fukinolic acid from Cimicifuga heracleifolia and its derivatives as novel antiviral compounds against enterovirus A71 infection.

Human enterovirus 71 (EV-A71) infections cause a wide array of diseases ranging from diarrhoea and rashes to hand-foot-and-mouth disease and, in rare cases, severe neurological disorders. No specific ...

New antiretroviral agent use affects prevalence of HIV drug resistance in clinical care populations.

To estimate the prevalence of HIV drug resistance over time and identify risk factors for multi-class resistance.

Disease-modifying treatment of amyotrophic lateral sclerosis.

Currently, there is no cure for amyotrophic lateral sclerosis (ALS) and the foundation of ALS management revolves around symptomatic and palliative care. Early diagnosis offers the best prognosis for ...

Clinical Trials [4472 Associated Clinical Trials listed on BioPortfolio]

An Evaluation of the Development of Nevirapine Induced Mutations in HIV Patients Initiating or Discontinuing Combination Antiretroviral Therapy

Hypothesis Nevirapine resistance developed in women and infants in the HIVNET 006 and 012 cohorts as a consequence of use of an agent with a long t½ as monotherapy in individuals with hi...

MIROCALS: Modifying Immune Response and OutComes in ALS

MIROCALS is a phase II study of ld-IL-2 as a therapeutic agent for ALS. A randomized (1:1), placebo-controlled, double-blind, parallel group trial will be carried out to assess ld-IL-2 saf...

Alkaline Diet for Insulin Sensitivity

The purpose of this study is to test the effect of increasing the body pH with an Alkaline agent (NaHCO3) on glucose homeostasis and insulin resistance in non diabetic subjects. The inves...

An Open-Label, Pilot Study to Evaluate the Development of Resistance to Nevirapine (BI-RG-587) in HIV-Infected Patients With CD4 Cell Count >= 500/mm3

Primary: To evaluate the rate of development of resistance to nevirapine in HIV-1 infected individuals. To evaluate safety of nevirapine in HIV-1 infected individuals with CD4 counts great...

The Durability of Response and Persistence of Resistance to AbbVie's 2 Direct-acting Antiviral Agent (2D) Therapy in Japanese Subjects

This study seeks to assess the durability of response and persistence of resistance to ombitasvir/ paritaprevir/ritonavir in Japanese participants who enrolled in a Phase 2 or 3 clinical s...

Medical and Biotech [MESH] Definitions

Antineoplastic agent especially effective against malignant brain tumors. The resistance which brain tumor cells acquire to the initial effectiveness of this drug can be partially overcome by the simultaneous use of membrane-modifying agents such as reserpine, calcium antagonists such as nicardipine or verapamil, or the calmodulin inhibitor, trifluoperazine. The drug has also been used in combination with other antineoplastic agents or with radiotherapy for the treatment of various neoplasms.

Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.


A type of strength-building exercise program that requires the body muscle to exert a force against some form of resistance, such as weight, stretch bands, water, or immovable objects. Resistance exercise is a combination of static and dynamic contractions involving shortening and lengthening of skeletal muscles.

A receptor activity-modifying protein that heterodimerizes with CALCITONIN RECEPTOR-LIKE PROTEIN to form the ADRENOMEDULLIN RECEPTOR. In addition, an isoform of the ISLET AMYLOID POLYPEPTIDE RECEPTOR is formed from this protein dimerizing with the CALCITONIN RECEPTOR.

Quick Search


DeepDyve research library

Relevant Topics

MRSA (methicillin-resistant Staphylococcus aureus)
MRSA (methicillin-resistant Staphylococcus aureus) is a family of bacteria with resistance to one or more major antibiotics. There are currently 17 different strains of MRSA. Two particular strains, EMRSA15 and EMRSA16  account for 96% of MRSA blood...

Drug Discovery
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...

Public Health
Alternative Medicine Cleft Palate Complementary & Alternative Medicine Congenital Diseases Dentistry Ear Nose & Throat Food Safety Geriatrics Healthcare Hearing Medical Devices MRSA Muscular Dyst...

Searches Linking to this Article