scholarly journals A marine microbiome antifungal targets urgent-threat drug-resistant fungi

Science ◽  
2020 ◽  
Vol 370 (6519) ◽  
pp. 974-978 ◽  
Author(s):  
Fan Zhang ◽  
Miao Zhao ◽  
Doug R. Braun ◽  
Spencer S. Ericksen ◽  
Jeff S. Piotrowski ◽  
...  
Keyword(s):  
Mode Of Action ◽  
Fungal Pathogens ◽  
Antifungal Drugs ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Candida Auris ◽  
Marine Animals ◽  
Multiple Drug Resistant

New antifungal drugs are urgently needed to address the emergence and transcontinental spread of fungal infectious diseases, such as pandrug-resistant Candida auris. Leveraging the microbiomes of marine animals and cutting-edge metabolomics and genomic tools, we identified encouraging lead antifungal molecules with in vivo efficacy. The most promising lead, turbinmicin, displays potent in vitro and mouse-model efficacy toward multiple-drug–resistant fungal pathogens, exhibits a wide safety index, and functions through a fungal-specific mode of action, targeting Sec14 of the vesicular trafficking pathway. The efficacy, safety, and mode of action distinct from other antifungal drugs make turbinmicin a highly promising antifungal drug lead to help address devastating global fungal pathogens such as C. auris.

scholarly journals Antitumor mechanism of evodiamine, a constituent from Chinese herb Evodiae fructus , in human multiple-drug resistant breast cancer NCI/ADR-RES cells in vitro and in vivo

2005 ◽  
Vol 26 (5) ◽  
pp. 968-975 ◽  
Author(s):  
Cho-Hwa Liao ◽  
Shiow-Lin Pan ◽  
Jih-Hwa Guh ◽  
Ya-Ling Chang ◽  
Hui-Chen Pai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Chinese Herb ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Multiple Drug Resistant

scholarly journals Klebsiella virus UPM2146 lyses multiple drug-resistant Klebsiella pneumoniae in vitro and in vivo

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245354
Author(s):  
Omar Assafiri ◽  
Adelene Ai-Lian Song ◽  
Geok Hun Tan ◽  
Irwan Hanish ◽  
Amalia Mohd Hashim ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Zebrafish Model ◽  
Whole Genome Analysis ◽  
Narrow Host Range ◽  
Opportunistic Bacteria ◽  
Multiple Drug Resistant

Klebsiella pneumoniae are opportunistic bacteria found in the gut. In recent years they have been associated with nosocomial infections. The increased incidence of multiple drug-resistant K. pneumoniae makes it necessary to find new alternatives to treat the disease. In this study, phage UPM2146 was isolated from a polluted lake which can lyse its host K. pneumoniae ATCC BAA-2146. Observation from TEM shows that UPM2146 belongs to Caudoviriales (Order) based on morphological appearance. Whole genome analysis of UPM2146 showed that its genome comprises 160,795 bp encoding for 214 putative open reading frames (ORFs). Phylogenetic analysis revealed that the phage belongs to Ackermannviridae (Family) under the Caudoviriales. UPM2146 produces clear plaques with high titers of 1010 PFU/ml. The phage has an adsorption period of 4 min, latent period of 20 min, rise period of 5 min, and releases approximately 20 PFU/ bacteria at Multiplicity of Infection (MOI) of 0.001. UPM2146 has a narrow host-range and can lyse 5 out of 22 K. pneumoniae isolates (22.72%) based on spot test and efficiency of plating (EOP). The zebrafish larvae model was used to test the efficacy of UPM2146 in lysing its host. Based on colony forming unit counts, UPM2146 was able to completely lyse its host at 10 hours onwards. Moreover, we show that the phage is safe to be used in the treatment against K. pneumoniae infections in the zebrafish model.

scholarly journals Erratum to: Oncolytic virus efficiency inhibited growth of tumour cells with multiple drug resistant phenotype in vivo and in vitro

2016 ◽  
Vol 14 (1) ◽  
Author(s):  
Elena P. Goncharova ◽  
Julia S. Ruzhenkova ◽  
Ivan S. Petrov ◽  
Sergey N. Shchelkunov ◽  
Marina A. Zenkova
Keyword(s):  
Oncolytic Virus ◽  
Tumour Cells ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Resistant Phenotype ◽  
Multiple Drug Resistant ◽  
Drug Resistant Phenotype

scholarly journals Oncolytic virus efficiency inhibited growth of tumour cells with multiple drug resistant phenotype in vivo and in vitro

2016 ◽  
Vol 14 (1) ◽  
Author(s):  
Elena P. Goncharova ◽  
Julia S. Ruzhenkova ◽  
Ivan S. Petrov ◽  
Sergey N. Shchelkunov ◽  
Marina A. Zenkova
Keyword(s):  
Oncolytic Virus ◽  
Tumour Cells ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Resistant Phenotype ◽  
Multiple Drug Resistant ◽  
Drug Resistant Phenotype

scholarly journals trans-Translation inhibitors bind to a novel site on the ribosome and clear Neisseria gonorrhoeae in vivo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zachary D. Aron ◽  
Atousa Mehrani ◽  
Eric D. Hoffer ◽  
Kristie L. Connolly ◽  
Pooja Srinivas ◽  
...  
Keyword(s):  
Oral Dose ◽  
Neisseria Gonorrhoeae ◽  
Multiple Drug ◽  
Specific Inhibition ◽  
Drug Resistant ◽  
Peptidyl Transfer ◽  
Bacterial Ribosome ◽  
Multiple Drug Resistant ◽  
Unique Site

AbstractBacterial ribosome rescue pathways that remove ribosomes stalled on mRNAs during translation have been proposed as novel antibiotic targets because they are essential in bacteria and are not conserved in humans. We previously reported the discovery of a family of acylaminooxadiazoles that selectively inhibit trans-translation, the main ribosome rescue pathway in bacteria. Here, we report optimization of the pharmacokinetic and antibiotic properties of the acylaminooxadiazoles, producing MBX-4132, which clears multiple-drug resistant Neisseria gonorrhoeae infection in mice after a single oral dose. Single particle cryogenic-EM studies of non-stop ribosomes show that acylaminooxadiazoles bind to a unique site near the peptidyl-transfer center and significantly alter the conformation of ribosomal protein bL27, suggesting a novel mechanism for specific inhibition of trans-translation by these molecules. These results show that trans-translation is a viable therapeutic target and reveal a new conformation within the bacterial ribosome that may be critical for ribosome rescue pathways.

In-vitro and intracellular activity of rifabutin on drug-susceptible and multiple drug-resistant (MDR) tubercle bacilli

1995 ◽  
Vol 36 (2) ◽  
pp. 355-363 ◽  
Author(s):  
Julieta Luna-Herrera ◽  
M. Venkata Reddy ◽  
Pattisapu R. J. Gangadharam
Keyword(s):  
Multiple Drug ◽  
Drug Resistant ◽  
Intracellular Activity ◽  
Multiple Drug Resistant

scholarly journals Hope in the Treatment of Candida Vaginitis: Ibrexafungerp

2021 ◽  
Author(s):  
Ayşe Sultan Karakoyun
Keyword(s):  
Current Knowledge ◽  
Public Health Problem ◽  
Clinical Findings ◽  
Antifungal Drugs ◽  
Drug Resistant ◽  
Over The Counter ◽  
Synthase Inhibitor ◽  
Increased Activity

Candida vaginitis (CV) is a neglected but growing public health problem. It is estimated that three out of four women have had at least one CV attack. The diagnosis and treatment of CV is often inadequate due to the tendency of women to self-diagnose and use over-the-counter drugs when they have vaginal or vulvar complaints, and clinicians plan treatment only according to clinical findings. There are limitations regarding the safety and efficacy of oral azoles, which are primarily preferred for the treatment of vaginitis, and these drugs have not revealed the desired levels of clinical or mycological cure. Also, there are a few options for current drugs used for treatment are not numerous the development of new antifungal drugs is thus urgently needed. Ibrexafungerp (IBX) is a semisynthetic triterpenoid glucan synthase inhibitor derived from enfumafungin. IBX has been shown to be a promising oral antifungal in the treatment of acute CV, and its use was approved on June 1, 2021. IBX is remarkable by it’s high oral bioavailability, low risk of side effects, few drug-drug interactions, good tissue penetration, increased activity at low pH in the vagina, and efficacy with regard to multi-drug-resistant fungi. In this review, in vitro and in vivo data on IBX were evaluated and compiled in light of current knowledge.

scholarly journals Antifungal Activity of an Original Amino-Isocyanonaphthalene (ICAN) Compound Family: Promising Broad Spectrum Antifungals

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 903
Author(s):  
Miklós Nagy ◽  
Gábor Szemán-Nagy ◽  
Alexandra Kiss ◽  
Zsolt László Nagy ◽  
László Tálas ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Candida Species ◽  
Fungal Pathogens ◽  
Clinical Strain ◽  
Control Group ◽  
Multiple Drug ◽  
Species Structure ◽  
In Vivo Experiments

Multiple drug resistant fungi pose a serious threat to human health, therefore the development of completely new antimycotics is of paramount importance. The in vitro antifungal activity of the original, 1-amino-5-isocyanonaphthalenes (ICANs) was evaluated against reference strains of clinically important Candida species. Structure-activity studies revealed that the naphthalene core and the isocyano- together with the amino moieties are all necessary to exert antifungal activity. 1,1-N-dimethylamino-5-isocyanonaphthalene (DIMICAN), the most promising candidate, was tested further in vitro against clinical isolates of Candida species, yielding a minimum inhibitory concentration (MIC) of 0.04–1.25 µg/mL. DIMICAN was found to be effective against intrinsically fluconazole resistant Candida krusei isolates, too. In vivo experiments were performed in a severly neutropenic murine model inoculated with a clinical strain of Candida albicans. Daily administration of 5 mg/kg DIMICAN intraperitoneally resulted in 80% survival even at day 13, whereas 100% of the control group died within six days. Based on these results, ICANs may become an effective clinical lead compound family against fungal pathogens.

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