scholarly journals Withdrawal: Rationally designed transmembrane peptide mimics of the multidrug transporter protein Cdr1 act as antagonists to selectively block drug efflux and chemosensitize azole-resistant clinical isolates of Candida albicans.

2020 ◽  
Vol 295 (10) ◽  
pp. 3393-3393
Author(s):  
Indresh Kumar Maurya ◽  
Chaitanya Kumar Thota ◽  
Sachin Dev Verma ◽  
Jyotsna Sharma ◽  
Manpreet Kaur Rawal ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Clinical Isolates ◽  
Multidrug Transporter ◽  
Drug Efflux ◽  
Peptide Mimics ◽  
Transporter Protein

scholarly journals Rationally Designed Transmembrane Peptide Mimics of the Multidrug Transporter Protein Cdr1 Act as Antagonists to Selectively Block Drug Efflux and Chemosensitize Azole-resistant Clinical Isolates of Candida albicans

2013 ◽  
Vol 288 (23) ◽  
pp. 16775-16787 ◽  
Author(s):  
Indresh Kumar Maurya ◽  
Chaitanya Kumar Thota ◽  
Sachin Dev Verma ◽  
Jyotsna Sharma ◽  
Manpreet Kaur Rawal ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Multidrug Resistance ◽  
Fluorescent Dyes ◽  
Single Photon ◽  
Specific Interaction ◽  
Antifungal Drugs ◽  
Clinical Isolates ◽  
Drug Efflux ◽  
Peptide Mimics ◽  
Fluorescence Measurements

Drug-resistant pathogenic fungi use several families of membrane-embedded transporters to efflux antifungal drugs from the cells. The efflux pump Cdr1 (Candida drug resistance 1) belongs to the ATP-binding cassette (ABC) superfamily of transporters. Cdr1 is one of the most predominant mechanisms of multidrug resistance in azole-resistant (AR) clinical isolates of Candida albicans. Blocking drug efflux represents an attractive approach to combat the multidrug resistance of this opportunistic human pathogen. In this study, we rationally designed and synthesized transmembrane peptide mimics (TMPMs) of Cdr1 protein (Cdr1p) that correspond to each of the 12 transmembrane helices (TMHs) of the two transmembrane domains of the protein to target the primary structure of the Cdr1p. Several FITC-tagged TMPMs specifically bound to Cdr1p and blocked the efflux of entrapped fluorescent dyes from the AR (Gu5) isolate. These TMPMs did not affect the efflux of entrapped fluorescent dye from cells expressing the Cdr1p homologue Cdr2p or from cells expressing a non-ABC transporter Mdr1p. Notably, the time correlation of single photon counting fluorescence measurements confirmed the specific interaction of FITC-tagged TMPMs with their respective TMH. By using mutant variants of Cdr1p, we show that these TMPM antagonists contain the structural information necessary to target their respective TMHs of Cdr1p and specific binding sites that mediate the interactions between the mimics and its respective helix. Additionally, TMPMs that were devoid of any demonstrable hemolytic, cytotoxic, and antifungal activities chemosensitize AR clinical isolates and demonstrate synergy with drugs that further improved the therapeutic potential of fluconazole in vivo.

Promiscuous partnering and independent activity of MexB, the multidrug transporter protein from Pseudomonas aeruginosa

2010 ◽  
Vol 430 (2) ◽  
pp. 355-364 ◽  
Author(s):  
Alexander Welch ◽  
Chidiebere U. Awah ◽  
Shiheng Jing ◽  
Hendrik W. van Veen ◽  
Henrietta Venter
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Drug Transport ◽  
Efflux Pump ◽  
Multidrug Transporter ◽  
Drug Efflux ◽  
Transporter Protein ◽  
Functional Complex ◽  
Drug Efflux Pump ◽  
Key Questions

The MexAB–OprM drug efflux pump is central to multidrug resistance of Pseudomonas aeruginosa. The ability of the tripartite protein to confer drug resistance on the pathogen is crucially dependent on the presence of all three proteins of the complex. However, the role of each protein in the formation of the intact functional complex is not well understood. One of the key questions relates to the (in)ability of MexB to act independently of its cognitive partners, MexA and OprM. In the present study, we have demonstrated that, in the absence of MexA and OprM, MexB can: (i) recruit AcrA and TolC from Escherichia coli to form a functional drug-efflux complex; (ii) transport the toxic compound ethidium bromide in a Gram-positive organism where the periplasmic space and outer membrane are absent; and (iii) catalyse transmembrane chemical proton gradient (ΔpH)-dependent drug transport when purified and reconstituted into proteoliposomes. Our results represent the first evidence of drug transport by an isolated RND (resistance–nodulation–cell division)-type multidrug transporter, and provide a basis for further studies into the energetics of RND-type transporters and their assembly into multiprotein complexes.

Pathogenicity of Candida tropicalis and Candida albicans after gastrointestinal inoculation in mice

1980 ◽  
Vol 29 (2) ◽  
pp. 808-813 ◽  
Author(s):  
J R Wingard ◽  
J D Dick ◽  
W G Merz ◽  
G R Sandford ◽  
R Saral ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Mouse Model ◽  
Lung Tissue ◽  
Candida Tropicalis ◽  
Cytotoxic Drugs ◽  
Clinical Isolates ◽  
Yeast Cells ◽  
Gastrointestinal Mucosa ◽  
Compromised Host ◽  
Adult Mice

The ability of clinical isolates of Candida albicans and candida tropicalis to invade through normal and damaged gastrointestinal mucosa was determined. Adult mice were treated with either gentamicin or gentamicin and cytarabine. Suspensions of yeast cells (10(7)) were administered through a catheter intraesophageally. Invasion was determined by culturing liver, kidney, and lung tissue from mice sacrificed after 48 h. C. albicans and C. tropicalis were incapable of invading through normal gastrointestinal mucosa in mice treated only with gentamicin. Two isolates of C. tropicalis penetrated the damaged gastrointestinal mucosa in 69% (49 of 71) of mice treated with gentamicin and cytarabine. In contrast, three isolates of C. albicans penetrated he damaged gastrointestinal mucosa in only 23% (14 of 62) of mice. These results suggest that C. tropicalis is more capable of invading through damaged gastrointestinal mucosa than C. albicans. The observations in this mouse model parallel those seen in patients on cytotoxic drugs. Therefore, this model offers a tool for investigation of the pathogenicity of these organisms in a model analogous to the compromised host.

Comparison of 3 Alcohol Gels and 70% Ethyl Alcohol for Hand Hygiene

2008 ◽  
Vol 29 (10) ◽  
pp. 960-962 ◽  
Author(s):  
Mirian Nicéa Zarpellon ◽  
Vanessa Sarto Soares ◽  
Natal Rodrigo Albrecht ◽  
Douglas Ricardo da Silva Bergamasco ◽  
Lourdes Botelho Garcia ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Candida Albicans ◽  
Hand Hygiene ◽  
Serratia Marcescens ◽  
Ethyl Alcohol ◽  
Laboratory Study ◽  
Clinical Isolates ◽  
Methicillin Resistant ◽  
Human Volunteers

In a laboratory study, we demonstrated that 3 alcohol-based hand gels, commercially available in Brazil, were as effective as the traditional 70% ethyl alcohol (by weight) in removing clinical isolates of methicillin-resistant Staphylococcus aureus, Serratia marcescens, and Candida albicans from heavily contaminated hands of human volunteers.

scholarly journals Robust, Comprehensive Molecular, and Phenotypical Characterisation of Atypical Candida albicans Clinical Isolates From Bogotá, Colombia

2020 ◽  
Vol 10 ◽  
Author(s):  
Giovanni Rodríguez-Leguizamón ◽  
Andrés Ceballos-Garzón ◽  
Carlos F. Suárez ◽  
Manuel A. Patarroyo ◽  
Claudia M. Parra-Giraldo
Keyword(s):  
Candida Albicans ◽  
Galleria Mellonella ◽  
Opportunistic Pathogen ◽  
Clinical Isolates ◽  
High Genetic Diversity ◽  
Cluster Membership ◽  
Protein Mass ◽  
Molecular Tests ◽  
Well Differentiated ◽  
Clade 1

Candida albicans is commensal in human microbiota and is known to be the commonest opportunistic pathogen, having variable clinical outcomes that can lead to up to 60% mortality. Such wide clinical behaviour can be attributed to its phenotypical plasticity and high genetic diversity. This study characterised 10 Colombian clinical isolates which had already been identified as C. albicans by molecular tests; however, previous bioinformatics analysis of protein mass spectra and phenotypical characteristics has shown that this group of isolates has atypical behaviour, sharing characteristics of both C. africana and C. albicans. This study was aimed at evaluating atypical isolates’ pathogenic capability in the Galleria mellonella model; susceptibility profiles were determined and MLST was used for molecular characterisation. Cluster analysis, enabling unbiased bootstrap to classify the isolates and establish their cluster membership and e-BURST, was used for establishing clonal complexes (CC). Both approaches involved using representative MLST data from the 18 traditional C. albicans clades, as well as C. albicans-associated and minor species. Ten atypical isolates were distributed as follows: 6/10 (B71, B41, B60, R6, R41, and R282) were grouped into a statistically well-supported atypical cluster (AC) and constituted a differentiated CC 6; 2/10 of the isolates were clearly grouped in clade 1 and were concurrent in CC 4 (B80, B44). Another 2/10 atypical isolates were grouped in clade 10 and concurred in CC 7 (R425, R111); most atypical isolates were related to geographically distant isolates and some represented new ST. Isolates B41 and R41 in the AC had greater virulence. Isolate B44 was fluconazole-resistant and was grouped in clade 1. The atypical nature of the isolates studied here was demonstrated by the contrast between phenotypical traits (C. africana-like), molecular markers (C. albicans-like), virulence, and antifungal resistance, highlighting the widely described genetic plasticity for this genus. Our results showed that the atypical isolates forming well-differentiated groups belonged to C. albicans. Our findings could contribute towards developing molecular epidemiology approaches for managing hospital-acquired infection.

Detection of ERG11 Overexpression in Candida albicans isolates from environmental sources and clinical isolates treated with inhibitory and subinhibitory concentrations of fluconazole

Mycoses ◽  
2020 ◽  
Author(s):  
Josimary Morais Vasconcelos Oliveira ◽  
Josidel Conceição Oliver ◽  
Amanda Latércia Tranches Dias ◽  
Ana Carolina Barbosa Padovan ◽  
Ester Siqueira Caixeta ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Clinical Isolates ◽  
Subinhibitory Concentrations
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