scholarly journals Impact of the Peptide WMR-K on Dual-Species Biofilm Candida albicans/Klebsiella pneumoniae and on the Untargeted Metabolomic Profile

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 214
Author(s):  
Emilia Galdiero ◽  
Maria Michela Salvatore ◽  
Angela Maione ◽  
Federica Carraturo ◽  
Stefania Galdiero ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Klebsiella Pneumoniae ◽  
Therapeutic Potential ◽  
Metabolomic Profile ◽  
Microbial Association ◽  
Extracellular Metabolites ◽  
New Antibiotics ◽  
Treated Culture ◽  
Synthetic Antimicrobial Peptides

In recent years, the scientific community has focused on the development of new antibiotics to address the difficulties linked to biofilm-forming microorganisms and drug-resistant infections. In this respect, synthetic antimicrobial peptides (AMPs) are particularly regarded for their therapeutic potential against a broad spectrum of pathogens. In this work, the antimicrobial and antibiofilm activities of the peptide WMR-K towards single and dual species cultures of Candida albicans and Klebsiella pneumoniae were investigated. We found minimum inhibitory concentration (MIC) values for WMR-K of 10 µM for K. pneumoniae and of 200 µM for C. albicans. Furthermore, sub-MIC concentrations of peptide showed an in vitro inhibition of biofilm formation of mono and polymicrobial systems and also a good biofilm eradication even if higher concentrations of it are needed. In order to provide additional evidence for the effect of the examined peptide, a study of changes in extracellular metabolites excreted and/or uptaken from the culture medium (metabolomic footprinting) in the poly-microbial association of C. albicans and K. pneumoniae in presence and absence of WMR-K was performed. Comparing to the untreated dual species biofilm culture, the metabolomic profile of the WMR-K treated culture appears significantly altered. The differentially expressed compounds are mainly related to the primary metabolic pathways, including amino acids, trehalose, pyruvic acid, glycerol and vitamin B6.

scholarly journals Synthetic Antimicrobial Peptides Exhibit Two Different Binding Mechanisms to the Lipopolysaccharides Isolated from Pseudomonas aeruginosa and Klebsiella pneumoniae

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Hanbo Chai ◽  
William E. Allen ◽  
Rickey P. Hicks
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Antimicrobial Peptides ◽  
Inhibitory Activity ◽  
Binding Conformation ◽  
Cd Studies ◽  
Synthetic Antimicrobial Peptides ◽  
Activity Mechanism ◽  
Binding Mechanisms

Circular dichroism and 1H NMR were used to investigate the interactions of a series of synthetic antimicrobial peptides (AMPs) with lipopolysaccharides (LPS) isolated from Pseudomonas aeruginosa and Klebsiella pneumoniae. Previous CD studies with AMPs containing only three Tic-Oic dipeptide units do not exhibit helical characteristics upon interacting with small unilamellar vesicles (SUVs) consisting of LPS. Increasing the number of Tic-Oic dipeptide units to six resulted in five analogues with CD spectra that exhibited helical characteristics on binding to LPS SUVs. Spectroscopic and in vitro inhibitory data suggest that there are two possible helical conformations resulting from two different AMP-LPS binding mechanisms. Mechanism one involves a helical binding conformation where the AMP binds LPS very strongly and is not efficiently transported across the LPS bilayer resulting in the loss of inhibitory activity. Mechanism two involves a helical binding conformation where the AMP binds LPS very loosely and is efficiently transported across the LPS bilayer resulting in an increase in inhibitory activity. Mechanism three involves a nonhelical binding conformation where the AMP binds LPS very loosely and is efficiently transported across the LPS bilayer resulting in an increase in inhibitory activity.

scholarly journals In vitro evaluation of the antifungal activity of Marco (Ambrosia arborescens Mill.) and Matico (Aristeguietia glutinosa Lam.) on the pathogenic fungi that cause dermatomycosis (ringworm)

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 559
Author(s):  
Tatiana de los Ángeles Mosquera Tayupanta ◽  
Sandra Elizabeth Ayala Valarezo ◽  
Tatiana Alexandra Vasquez Villareal ◽  
María Belén Montaluisa Álvarez
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Trichophyton Rubrum ◽  
Therapeutic Potential ◽  
Pathogenic Fungi ◽  
Trichophyton Mentagrophytes ◽  
Microsporum Canis ◽  
The One ◽  
One Way Anova

Background: Currently, there is a trend towards using natural and ethnopharmacological species with therapeutic potential. This investigation evaluated the antifungal activity of two species in the Ecuadorian Andes, which are used in treating dermatomycosis: Ambrosia arborescens Mill. (Marco) and Aristeguietia glutinosa Lam. (Matico). Methods: We worked with seven concentrations (100 to 700ppm) of Ambrosia arborescens Mill. extract and ten concentrations (0.5 to 5%) of essential oil (EO) of Aristeguietia glutinosa Lam. on Trichophyton mentagrophytes ATCC 9533, Trichophyton rubrum ATCC 28188, Microsporum canis ATCC 36299 and Candida albicans ATCC 10231. The methodology used was a modified version of the Kirby-Bauer method, using diffusion in agar wells. Results: The Tukey test, after the one-way Anova, determined effective concentrations of EO: 5% for Trichophyton mentagrophytes, 4.5% for Trichophyton rubrum, 5% for Microsporum canis and 2% for Candida albicans. In the extracts, the concentration of 700ppm was used for Trichophyton mentagrophytes, Trichophyton rubrum, and 600ppm for Microsporum canis and Candida albicans. Conclusions: The evaluation of the antifungal activity of the Ambrosia arborescens extract showed inhibition in the studied dermatophytes in each one of the planted concentrations (100 to 700ppm). The evaluation of the antifungal activity of Aristeguietia glutinosa EO showed inhibition in the studied dermatophytes in each of the planted concentrations (0.5 to 5%).

scholarly journals Bacteriophages isolated from dairy farm mitigated Klebsiella pneumoniae-induced inflammation in bovine mammary epithelial cells cultured in vitro

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Yuxiang Shi ◽  
Wenpeng Zhao ◽  
Gang Liu ◽  
Tariq Ali ◽  
Peng Chen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Klebsiella Pneumoniae ◽  
Inflammatory Responses ◽  
Mammary Epithelial Cells ◽  
Therapeutic Potential ◽  
Morphological Changes ◽  
Mammary Epithelial ◽  
Bovine Mammary Epithelial Cells ◽  
Tnf Α

Abstract Background Klebsiella pneumoniae, an environmental pathogen causing mastitis in dairy cattle, is often resistant to antibiotics. K. pneumoniae was used as the host bacteria to support bacteriophage replication; 2 bacteriophages, CM8-1 and SJT-2 were isolated and considered to have therapeutic potential. In the present study, we determined the ability of these 2 bacteriophages to mitigate cytotoxicity, pathomorphological changes, inflammatory responses and apoptosis induced by K. pneumoniae (bacteriophage to K. pneumoniae MOI 1:10) in bovine mammary epithelial cells (bMECs) cultured in vitro. Results Bacteriophages reduced bacterial adhesion and invasion and cytotoxicity (lactate dehydrogenase release). Morphological changes in bMECs, including swelling, shrinkage, necrosis and hematoxylin and eosin staining of cytoplasm, were apparent 4 to 8 h after infection with K. pneumoniae, but each bacteriophage significantly suppressed damage and decreased TNF-α and IL-1β concentrations. K. pneumoniae enhanced mRNA expression of TLR4, NF-κB, TNF-α, IL-1β, IL-6, IL-8, caspase-3, caspase-9 and cyt-c in bMECs and increased apoptosis of bMECs, although these effects were mitigated by treatment with either bacteriophage for 8 h. Conclusions Bacteriophages CM8-1 and SJT-2 mitigated K. pneumoniae-induced inflammation in bMECs cultured in vitro. Therefore, the potential of these bacteriophages for treating mastitis in cows should be determined in clinical trials.

scholarly journals Mucins Suppress Virulence Traits of Candida albicans

mBio ◽  
2014 ◽  
Vol 5 (6) ◽  
Author(s):  
Nicole L. Kavanaugh ◽  
Angela Q. Zhang ◽  
Clarissa J. Nobile ◽  
Alexander D. Johnson ◽  
Katharina Ribbeck
Keyword(s):  
Gene Expression ◽  
Candida Albicans ◽  
Therapeutic Potential ◽  
Content Type ◽  
Environmental Signals ◽  
Healthy Humans ◽  
Normal Microbiota ◽  
Life Threatening ◽  
Main Components

ABSTRACTCandida albicansis the most prevalent fungal pathogen of humans, causing a variety of diseases ranging from superficial mucosal infections to deep-seated systemic invasions. Mucus, the gel that coats all wet epithelial surfaces, accommodatesC. albicansas part of the normal microbiota, whereC. albicansresides asymptomatically in healthy humans. Through a series ofin vitroexperiments combined with gene expression analysis, we show that mucin biopolymers, the main gel-forming constituents of mucus, induce a new oval-shaped morphology inC. albicansin which a range of genes related to adhesion, filamentation, and biofilm formation are downregulated. We also show that corresponding traits are suppressed, renderingC. albicansimpaired in forming biofilms on a range of different synthetic surfaces and human epithelial cells. Our data suggest that mucins can manipulateC. albicansphysiology, and we hypothesize that they are key environmental signals for retainingC. albicansin the host-compatible, commensal state.IMPORTANCEThe yeastCandida albicanscauses both superficial infections of the mucosa and life-threatening infections upon entering the bloodstream. However,C. albicansis not always harmful and can exist as part of the normal microbiota without causing disease. Internal body surfaces that are susceptible to infection byC. albicansare coated with mucus, which we hypothesize plays an important role in preventing infections. Here, we show that the main components of mucus, mucin glycoproteins, suppress virulence attributes ofC. albicansat the levels of gene expression and the corresponding morphological traits. Specifically, mucins suppress attachment to plastic surfaces and human cells, the transition to cell-penetrating hyphae, and the formation of biofilms (drug-resistant microbial communities). Additionally, exposure to mucins induces an elongated morphology that physically resembles the mating-competent opaque state but is phenotypically distinct. We suggest that mucins are potent antivirulence molecules that have therapeutic potential for suppressingC. albicansinfections.

scholarly journals Salivary Histatin 5 and Human Neutrophil Defensin 1 Kill Candida albicans via Shared Pathways

2000 ◽  
Vol 44 (12) ◽  
pp. 3310-3316 ◽  
Author(s):  
Mira Edgerton ◽  
Svetlana E. Koshlukova ◽  
Marcelo W. B. Araujo ◽  
Rashmi C. Patel ◽  
Jin Dong ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Human Neutrophil ◽  
Therapeutic Potential ◽  
Oral Candidiasis ◽  
Cytotoxic Action ◽  
Antimicrobial Proteins ◽  
Histatin 5 ◽  
Solution Structures ◽  
Atp Efflux

ABSTRACT Salivary histatins are a family of basic histidine-rich proteins in which therapeutic potential as drugs against oral candidiasis is apparent, considering their potent in vitro antifungal activity and lack of toxicity to humans. Histatin 5 (Hst 5) kills the fungal pathogen Candida albicans via a mechanism that involves binding to specific sites on the yeast cell membrane and subsequent release of cellular ATP in the absence of cytolysis. We explored the killing pathway activated by Hst 5 and compared it to those activated by other antifungal agents. The candidacidal activity of human neutrophil defensin 1 (HNP-1) shared very similar features to Hst 5 cytotoxic action with respect to active concentrations and magnitude of induction of nonlytic ATP efflux, depletion of intracellular ATP pools, and inhibitor profile. Hst 5 and HNP-1 are basic proteins of about 3 kDa; however, they have unique primary sequences and solution structures that cannot explain how these two molecules act so similarly on C. albicans to induce cell death. Our finding that HNP-1 prevented Hst 5 binding to the candidal Hst 5 binding protein suggests that the basis for the overlapping actions of these two naturally occurring antimicrobial proteins may involve interactions with shared yeast components.

scholarly journals GC-MS-Based Metabolomics Study of Single- and Dual-Species Biofilms of Candida albicans and Klebsiella pneumoniae

2021 ◽  
Vol 22 (7) ◽  
pp. 3496
Author(s):  
Emilia Galdiero ◽  
Maria Michela Salvatore ◽  
Angela Maione ◽  
Elisabetta de Alteriis ◽  
Anna Andolfi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amino Acid ◽  
Klebsiella Pneumoniae ◽  
Relative Abundance ◽  
Vitamin B6 ◽  
Microbial Composition ◽  
Extracellular Metabolites ◽  
Central Carbon ◽  
Metabolomics Study ◽  
Biofilm Community

Candida albicans and Klebsiella pneumoniae frequently co-exist within the human host as a complex biofilm community. These pathogens are of interest because their association is also related to significantly increased morbidity and mortality in hospitalized patients. With the aim of highlighting metabolic shifts occurring in the dual-species biofilm, an untargeted GC-MS-based metabolomics approach was applied to single and mixed biofilms of C. albicans and K. pneumoniae. Metabolomic results showed that among the extracellular metabolites identified, approximately 40 compounds had significantly changed relative abundance, mainly involving central carbon, amino acid, vitamin, and secondary metabolisms, such as serine, leucine, arabitol, phosphate, vitamin B6, cyclo-(Phe-Pro), trehalose, and nicotinic acid. The results were related to the strict interactions between the two species and the different microbial composition in the early and mature biofilms.

scholarly journals In-Vitro Evaluation of Antimicrobial Activities of Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Neisseria gonorrhoeae, and Candida albicans Nosodes

Homeopathy ◽  
2021 ◽  
Author(s):  
Renuka Munshi ◽  
Gitanjali Talele ◽  
Rajesh Shah
Keyword(s):  
Escherichia Coli ◽  
Candida Albicans ◽  
Klebsiella Pneumoniae ◽  
Neisseria Gonorrhoeae ◽  
Salmonella Typhi ◽  
Antimicrobial Activities ◽  
Positive Control ◽  
E Coli ◽  
Inhibition Of Growth

Abstract Background This study presents the results of the minimum inhibitory concentration (MIC) assay of a series of nosodes: namely Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Neisseria gonorrhoeae, and Candida albicans. Each was tested against its corresponding infection as well as cross infections. Methods In-vitro efficacy of polyvalent nosodes was tested using the MIC assay technique. The nosodes, namely C. albicans polyvalent nosode (35c, 100c), N. gonorrhoeae (35c), K. pneumoniae (35c, 100c), E. coli polyvalent nosode (35c, 100c) and Salmonella typhi polyvalent nosode (30c, 100c), were tested along with positive and negative controls. Nosodes were studied in different potencies and at 1:1 dilution. Results C. albicans polyvalent nosode 35c, 100c, N. gonorrhoeae 35c, and positive control amphotericin B showed inhibition of the growth of C. albicans species. K. pneumoniae 35c, E. coli polyvalent nosode 100c, and meropenem (positive control) showed inhibition of the growth of K. pneumoniae; this effect was not seen with ceftriaxone, ofloxacin and amoxicillin antibiotics. E. coli polyvalent nosode 30c in 10% alcohol (direct and dilution 1:1) and the positive controls ciprofloxacin, ofloxacin, and amoxicillin showed inhibition of the growth of E. coli. The S. typhi polyvalent nosode 30c in 10% alcohol showed inhibition of growth of S. typhi. Conclusion This study reveals that the tested nosodes exhibited antibacterial potential against the corresponding micro-organisms and against other selected organisms studied using this assay.

Preparation and Standardization of Nosodes Sourced from Klebsiella Pneumoniae, Salmonella Typhi, Neisseria Gonorrhoeae and Candida Albicans Strains

Homeopathy ◽  
2021 ◽  
Author(s):  
Renuka Munshi ◽  
Gitanjali Talele ◽  
Rajesh Shah
Keyword(s):  
Candida Albicans ◽  
Klebsiella Pneumoniae ◽  
Neisseria Gonorrhoeae ◽  
Material Culture ◽  
Therapeutic Potential ◽  
Biological Effects ◽  
Salmonella Typhi ◽  
Molecular Testing ◽  
Test Results ◽  
Bacterial Strains

Abstract Background Homeopathic nosodes prepared from organisms and pathological tissues have shown biological effects, encouraging more research. There is a need to develop some new nosodes systematically and to re-make others that were developed over a century ago. In our program of work on nosodes, the bacterial strains Klebsiella pneumoniae (BAA 2146), Salmonella typhi and Neisseria gonorrhoeae (ATCC 43069), and the single-celled fungus Candida albicans (24433, 26790, and 60193) have been identified for preparation. Materials and Methods The systematic and scientific method of preparation of nosodes includes identification, culture, quantification, characterization, preparation, and standardization. Under laminar flow, a suspension of respective bacterial and fungal cells (20 billion cells/mL) was processed as per the Homoeopathic Pharmacopoeia of India (HPI). Culture tests, sterility tests and molecular testing (polymerase chain reaction) were performed to establish the absence of contamination, live organisms and DNA material. Results K. pneumoniae, S. typhi (single, bivalent, or polyvalent), N. gonorrhoeae, and C. albicans nosodes (single and polyvalent) were sourced and prepared from different strains of respective cultures. The nosode preparations were processed by serial dilution and potentization, normally following the HPI guidelines. Molecular test results showed the absence of live organisms or DNA material; culture and sterility test results demonstrated the safety profile of the potentized nosodes. Conclusion K. pneumoniae, S. typhi, N. gonorrhoeae and C. albicans nosodes were successfully prepared. Their therapeutic potential may now be evaluated.

scholarly journals Effects of Echinocandins in Combination with Nikkomycin Z against Invasive Candida albicans Bloodstream Isolates and the fks Mutants

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Yuk-Yam Cheung ◽  
Mamie Hui
Keyword(s):  
Candida Albicans ◽  
Therapeutic Potential ◽  
Synergistic Effects ◽  
Rank Test ◽  
Content Type ◽  
Log Rank Test ◽  
Echinocandin Resistance ◽  
Nikkomycin Z

ABSTRACT We evaluated the in vitro and in vivo effects of nikkomycin Z combined with an echinocandin (anidulafungin or micafungin) against two Candida albicans isolates and their lab-derived echinocandin-resistant fks mutants with FKS1 S645Y and FKS1 S645P. Synergistic effects were observed in all tested strains (fractional inhibitory concentration index, <0.5). Enhanced survival was observed in an immunocompromised murine model (log-rank test, P < 0.02). Our study demonstrated the therapeutic potential of nikkomycin Z-echinocandin combinations in managing echinocandin resistance.

scholarly journals In Vitro Selection oframRandsoxRMutants Overexpressing Efflux Systems by Fluoroquinolones as Well as Cefoxitin in Klebsiella pneumoniae

2011 ◽  
Vol 55 (6) ◽  
pp. 2795-2802 ◽  
Author(s):  
Suzanne Bialek-Davenet ◽  
Estelle Marcon ◽  
Véronique Leflon-Guibout ◽  
Jean-Philippe Lavigne ◽  
Frédéric Bert ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
In Vitro Selection ◽  
Efflux Pump ◽  
Clinical Isolates ◽  
Cross Resistance ◽  
Efflux System ◽  
Content Type ◽  
New Antibiotics ◽  
Regulator Genes

ABSTRACTThe relationship between efflux system overexpression and cross-resistance to cefoxitin, quinolones, and chloramphenicol has recently been reported inKlebsiella pneumoniae. In 3 previously published clinical isolates and 17in vitromutants selected with cefoxitin or fluoroquinolones, mutations in the potential regulator genes of the AcrAB efflux pump (acrR,ramR,ramA,marR,marA,soxR,soxS, androb) were searched, and their impacts on efflux-related antibiotic cross-resistance were assessed. All mutants but 1, and 2 clinical isolates, overexpressedacrB. No mutation was detected in the regulator genes studied among the clinical isolates and 8 of the mutants. For the 9 remaining mutants, a mutation was found in theramRgene in 8 of them and in thesoxRgene in the last one, resulting in overexpression oframAandsoxS, respectively. Transformation of theramRmutants and thesoxRmutant with the wild-typeramRandsoxRgenes, respectively, abolished overexpression ofacrBandramAin theramRmutants and ofsoxSin thesoxRmutant, as well as antibiotic cross-resistance. Resistance due to efflux system overexpression was demonstrated for 4 new antibiotics: cefuroxime, cefotaxime, ceftazidime, and ertapenem. This study shows that theramRandsoxRgenes control the expression of efflux systems inK. pneumoniaeand suggests the existence of efflux pumps other than AcrAB and of other loci involved in the regulation of AcrAB expression.

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