Dioscin Inhibits Virulence Factors ofCandida albicans

Candida albicansinfections present a heavy burden upon public health, with only a few drugs available, while biofilms formed byC. albicansworsen this situation. Dioscin has antitumor, anti-inflammatory, and hepatoprotective effects, and this study was conducted to evaluate the effects of dioscin on the biofilm formation and development, as well as other virulence factors ofC. albicanssuch as morphological transition, adhesion, and extracellular secreted phospholipase. Our results showed dioscin inhibits these virulence factors and has low cytotoxicity against mammalian cells. Considering protective effects of dioscin against damage on liver and kidney, dioscin may be used as a potential candidate for antifungal development.

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Lycorine Hydrochloride Inhibits the Virulence Traits ofCandida albicans

BioMed Research International ◽

10.1155/2019/1851740 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10

Author(s):

Longfei Yang ◽

Xin Liu ◽

Yujie Sui ◽

Zhiming Ma ◽

Xuechao Feng ◽

...

Keyword(s):

Fungal Pathogen ◽

Biofilm Formation ◽

Mammalian Cells ◽

Inhibitory Concentration ◽

Antifungal Drugs ◽

Exopolymeric Substances ◽

Health Burden ◽

Ofcandida Albicans ◽

Opportunistic Fungal Pathogen ◽

Potential Use

The human opportunistic fungal pathogenCandida albicanscauses a severe health burden while the biofilms formed byC. albicanspresent a kind of infections that are hard to cure, highlighting the pressing need for new antifungal drugs againstC. albicans. This study was to explore the antifungal activities of lycorine hydrochloride (LH) againstC. albicans. The minimal inhibitory concentration (MIC) of LH againstC. albicansSC5314 was 64μM. Below its MIC, LH demonstrated antivirulence property by suppressing adhesion, filamentation, biofilm formation, and development, as well as the production of extracellular phospholipase and exopolymeric substances (EPS). The cytotoxicity of LH against mammalian cells was low, with half maximal inhibitory concentrations (IC50) above 256μM. Moreover, LH showed a synergistic effect with AmB, although its interaction with fluconazole, as well as caspofungin, was indifferent. Thus, our study reports the potential use of LH, alone or in combination with current antifungal drugs, to fightC. albicansinfections.

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The effect of some chemical materials against virulence factors of Candida ssp isolated from UTI patients

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v9ispl1.1318 ◽

2018 ◽

Vol 9 (SPL1) ◽

Author(s):

Fatima Abdul Hussein Mejbel

Keyword(s):

Urinary Tract Infection ◽

Urinary Tract ◽

Tract Infection ◽

Virulence Factors ◽

Biofilm Formation ◽

Germ Tube ◽

Laboratory Culture ◽

Candida Spp ◽

Other Substances ◽

Chemical Materials

During the period from September 2016 to December 2017,135 urine samples were collected from urinary tract infection patients attending to AL-Zahraa Hospital in AL-Najaf Governorate. The present study was conducted to isolate and identify Candida spp. isolated from urinary tract infection patients by different methods including direct examination, laboratory culture, biochemical test and by modern techniques (Api Candida kit) and determine the virulence factors phenotypic to Candida spp which involved (biofilm formation,phospholipase and germ tube). The percentage of females to males was as following, female (84) 62.2 % (21) infected and male (51) 37.8% (1) infected with all age categories. The results in this study are explain that is some Candida spp. such as C. albicans, have high susceptible to eugenole follow by phenol and umbellulone. The efficiency of some chemical substances such as (eugenole,umbellulone, and phenol) was evaluated to inhibit the growth of Candida ssp as well as some virulence factors such as biofilm formation,germ tube and phospholipase,which were studied in this research. Statistically analysis results have been significance difference between the results of the substance concentrations and the concentrations of the different other substances.

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Quorum Sensing – A Stratagem for Conquering Multi-Drug Resistant Pathogens

Current Pharmaceutical Design ◽

10.2174/1381612826666201210105638 ◽

2020 ◽

Vol 26 ◽

Author(s):

Madison Tonkin ◽

Shama Khan ◽

Mohmmad Younus Wani ◽

Aijaz Ahmad

Keyword(s):

Drug Resistance ◽

Quorum Sensing ◽

Virulence Factors ◽

Biofilm Formation ◽

Cell Communication ◽

Natural Compounds ◽

Quorum Sensing Inhibitors ◽

Communication Technique ◽

Multicellular Organisms ◽

Chemical Strategies

: Quorum sensing is defined as cell to cell communication between microorganisms, which enables microorganisms to behave as multicellular organisms. Quorum sensing enables many collaborative benefits such as synchronisation of virulence factors and biofilm formation. Both quorum sensing as well as biofilm formation encourage the development of drug resistance in microorganisms. Biofilm formation and quorum sensing are causally linked to each other and play role in the pathogenesis of microorganisms. With the increasing drug resistance against the available antibiotics and antifungal medications, scientists are combining different options to develop new strategies. Such strategies rely on the inhibition of the communication and virulence factors rather than on killing or inhibiting the growth of the microorganisms. This review encompasses the communication technique used by microorganisms, how microorganism resistance is linked to quorum sensing and various chemical strategies to combat quorum sensing and thereby drug resistance. Several compounds have been identified as quorum sensing inhibitors and are known to be effective in reducing resistance as they do not kill the pathogens but rather disrupt their communication. Natural compounds have been identified as anti-quorum sensing agents. However, natural compounds present several related disadvantages. Therefore, the need for the development of synthetic or semi-synthetic compounds has arisen. This review argues that anti-quorum sensing compounds are effective in disrupting quorum sensing and could therefore be effective in reducing microorganism drug resistance.

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Synthesis and Structure−Activity Relationship Studies of N-monosubstituted Aroylthioureas as Urease Inhibitors

Medicinal Chemistry ◽

10.2174/1573406416999200818152440 ◽

2020 ◽

Vol 16 ◽

Author(s):

Wei-Wei Ni ◽

Hai-Lian Fang ◽

Ya-Xi Ye ◽

Wei-Yi Li ◽

Li Liu ◽

...

Keyword(s):

Regression Analysis ◽

Mammalian Cells ◽

Intact Cell ◽

Linear Regression Analysis ◽

Positive Control ◽

Acetohydroxamic Acid ◽

Urease Inhibitors ◽

Ic50 Value ◽

Ic50 Values ◽

Low Cytotoxicity

Background: Thiourea is a classical urease inhibitor usually as a positive control, and many N,N`-disubstituted thioureas have been determined as urease inhibitors. However, due to steric hindrance, N,N`-disubstituted thiourea motif could not bind urease as thiourea. On the contrary, N-monosubstituted thioureas with a tiny thiourea motif could theoretically bind into the active pocket as thiourea. Objective: A series of N-monosubstituted aroylthioureas were designed and synthesized for evaluation as urease inhibitors. Methods: Urease inhibition was determined by the indophenol method and IC50 values were calculated using computerized linear regression analysis of quantal log dose-probit functions. The kinetic parameters were estimated viasurface plasmon resonance (SPR) and by nonlinear regression analysis based on the mixed type inhibition model derived from Michaelis-Menten kinetics. Results: Compounds b2, b11and b19 reversibly inhibited urease with a mixed mechanism, and showed excellent potency against both cell-free urease and urease in intact cell, with IC50 values being 90-to 450-fold and 5-to 50-fold lower than the positive control acetohydroxamic acid, respectively. The most potent compound b11 showed IC50 value of 0.060 ±0.004μM against cell-free urease, which bound to urea binding site with a very low KDvalue (0.420±0.003nM) and a very long residence time (6.7 min). Compound b11was also demonstrated having very low cytotoxicity to mammalian cells. Conclusion: These results revealed that N-monosubstituted aroylthioureas clearly bind the active site of urease as expected, and represent a new class of urease inhibitors for the development of potential therapeutics against infections caused by ure-ase-containing pathogens.

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Exploiting DNA Endonucleases to Advance Mechanisms of DNA Repair

Biology ◽

10.3390/biology10060530 ◽

2021 ◽

Vol 10 (6) ◽

pp. 530

Author(s):

Marlo K. Thompson ◽

Robert W. Sobol ◽

Aishwarya Prakash

Keyword(s):

Dna Repair ◽

Mammalian Cells ◽

Genome Stability ◽

Gene Editing ◽

Adaptive Immune System ◽

Zinc Finger Nucleases ◽

Specific Gene ◽

Target Sequence ◽

Transcription Activator ◽

Low Cytotoxicity

The earliest methods of genome editing, such as zinc-finger nucleases (ZFN) and transcription activator-like effector nucleases (TALENs), utilize customizable DNA-binding motifs to target the genome at specific loci. While these approaches provided sequence-specific gene-editing capacity, the laborious process of designing and synthesizing recombinant nucleases to recognize a specific target sequence, combined with limited target choices and poor editing efficiency, ultimately minimized the broad utility of these systems. The discovery of clustered regularly interspaced short palindromic repeat sequences (CRISPR) in Escherichia coli dates to 1987, yet it was another 20 years before CRISPR and the CRISPR-associated (Cas) proteins were identified as part of the microbial adaptive immune system, by targeting phage DNA, to fight bacteriophage reinfection. By 2013, CRISPR/Cas9 systems had been engineered to allow gene editing in mammalian cells. The ease of design, low cytotoxicity, and increased efficiency have made CRISPR/Cas9 and its related systems the designer nucleases of choice for many. In this review, we discuss the various CRISPR systems and their broad utility in genome manipulation. We will explore how CRISPR-controlled modifications have advanced our understanding of the mechanisms of genome stability, using the modulation of DNA repair genes as examples.

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Baicalin Represses Type Three Secretion System of Pseudomonas aeruginosa through PQS System

Molecules ◽

10.3390/molecules26061497 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1497

Author(s):

Pansong Zhang ◽

Qiao Guo ◽

Zhihua Wei ◽

Qin Yang ◽

Zisheng Guo ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Virulence Factors ◽

Mammalian Cells ◽

Secretion System ◽

Chinese Herbs ◽

Infection Model ◽

Lung Pathology ◽

Promising Alternative ◽

The Impact

Therapeutics that target the virulence of pathogens rather than their viability offer a promising alternative for treating infectious diseases and circumventing antibiotic resistance. In this study, we searched for anti-virulence compounds against Pseudomonas aeruginosa from Chinese herbs and investigated baicalin from Scutellariae radix as such an active anti-virulence compound. The effect of baicalin on a range of important virulence factors in P. aeruginosa was assessed using luxCDABE-based reporters and by phenotypical assays. The molecular mechanism of the virulence inhibition by baicalin was investigated using genetic approaches. The impact of baicalin on P. aeruginosa pathogenicity was evaluated by both in vitro assays and in vivo animal models. The results show that baicalin diminished a plenty of important virulence factors in P. aeruginosa, including the Type III secretion system (T3SS). Baicalin treatment reduced the cellular toxicity of P. aeruginosa on the mammalian cells and attenuated in vivo pathogenicity in a Drosophila melanogaster infection model. In a rat pulmonary infection model, baicalin significantly reduced the severity of lung pathology and accelerated lung bacterial clearance. The PqsR of the Pseudomonas quinolone signal (PQS) system was found to be required for baicalin’s impact on T3SS. These findings indicate that baicalin is a promising therapeutic candidate for treating P. aeruginosa infections.

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Virulence Factors in Coagulase-Negative Staphylococci

Pathogens ◽

10.3390/pathogens10020170 ◽

2021 ◽

Vol 10 (2) ◽

pp. 170

Author(s):

Angela França ◽

Vânia Gaio ◽

Nathalie Lopes ◽

Luís D. R. Melo

Keyword(s):

Antibiotic Resistance ◽

Virulence Factors ◽

Resistance Genes ◽

Biofilm Formation ◽

Antibiotic Resistance Genes ◽

Coagulase Negative Staphylococci ◽

Healthcare Associated ◽

Major Pathogens

Coagulase-negative staphylococci (CoNS) have emerged as major pathogens in healthcare-associated facilities, being S. epidermidis, S. haemolyticus and, more recently, S. lugdunensis, the most clinically relevant species. Despite being less virulent than the well-studied pathogen S. aureus, the number of CoNS strains sequenced is constantly increasing and, with that, the number of virulence factors identified in those strains. In this regard, biofilm formation is considered the most important. Besides virulence factors, the presence of several antibiotic-resistance genes identified in CoNS is worrisome and makes treatment very challenging. In this review, we analyzed the different aspects involved in CoNS virulence and their impact on health and food.

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