scholarly journals A mutation in the glycosyltransferase gene lafB causes daptomycin hypersusceptibility in Enterococcus faecium

2019 ◽  
Vol 75 (1) ◽  
pp. 36-45 ◽  
Author(s):  
Suelen S Mello ◽  
Daria Van Tyne ◽  
Francois Lebreton ◽  
Simone Q Silva ◽  
Mara C L Nogueira ◽  
...  
Keyword(s):  
Enterococcus Faecium ◽  
Acid Metabolism ◽  
Lipoteichoic Acid ◽  
Genetic Alterations ◽  
Naturally Occurring ◽  
New Information ◽  
Susceptible Isolate ◽  
Mutant Derivative ◽  
Genome Comparisons

Abstract Objectives To verify dissemination of daptomycin-non-susceptible Enterococcus faecium in a hospital where daptomycin was not in use and to understand the evolutionary pathways connecting daptomycin hypersusceptibility to non-susceptibility. Methods Clonality of 26 E. faecium was assessed by PFGE and the STs of these isolates were determined. The most daptomycin-susceptible isolate was evolved in vitro by stepwise daptomycin selection, generating isolates for genome comparisons. Results The spread of a high-risk daptomycin-non-susceptible VRE clone was detected, as was the occurrence of an unusual daptomycin-hypersusceptible strain (HBSJRP18). To determine the basis for daptomycin hypersusceptibility, we evolved HBSJRP18 in vitro and identified candidate genetic alterations potentially related to daptomycin susceptibility. Both lafB, encoding glycosyltransferase, which is putatively involved in lipoteichoic acid (LTA) biosynthesis, and dak, encoding a dihydroxyacetone kinase likely involved in fatty acid metabolism, were mutated in multiple independent experiments. Trans-complementation showed that the lafB polymorphism naturally occurring in HBSJRP18 caused its daptomycin hypersusceptibility. Fourier-transform infrared spectroscopy identified differences between the extracted LTA spectra from the hypersusceptible isolate and its revertant, as well as other non-susceptible variants, supporting a role for LafB in E. faecium LTA biosynthesis. Zeta potential difference was detected in one evolved dak mutant derivative. While much more susceptible to daptomycin, HBSJRP18 showed enhanced growth in the presence of piperacillin, suggesting that this, or another cell wall-targeting antibiotic, may have selected for the daptomycin-hypersusceptible phenotype. Conclusions Our findings provide new information on the basis for daptomycin susceptibility in E. faecium, with implications for limiting the development and spread of daptomycin resistance.

scholarly journals Enterococcal surface protein contributes to persistence in the host but is not a target of opsonic and protective antibodies in Enterococcus faecium infection

2010 ◽  
Vol 59 (9) ◽  
pp. 1001-1004 ◽  
Author(s):  
I. G. Sava ◽  
E. Heikens ◽  
A. Kropec ◽  
C. Theilacker ◽  
R. Willems ◽  
...  
Keyword(s):  
Enterococcus Faecium ◽  
Passive Immunization ◽  
Surface Protein ◽  
Lipoteichoic Acid ◽  
Polyclonal Antiserum ◽  
Clinical Isolates ◽  
Rabbit Serum ◽  
Normal Rabbit Serum ◽  
Protective Antibodies

Enterococci are important nosocomial pathogens with multiple intrinsic and acquired resistances to antibiotics. In the past, the majority of infections were caused by Enterococcus faecalis; however, an increase in Enterococcus faecium clinical isolates has been observed in recent years. The enterococcal surface protein (Esp) is expressed on the surface of most E. faecium clinical isolates and has been shown to be involved in biofilm formation. Here, E. faecium E1162 and its previously created insertion-deletion mutant of the esp gene, E. faecium E1162Δesp, were compared in a mouse bacteraemia model. Anti-Esp serum was tested for its capacity to mediate opsonophagocytic killing of E1162 in vitro and to protect against E. faecium bacteraemia. The inactivation of esp attenuated E. faecium virulence with reduced numbers of bacteria recovered from the kidneys in animals infected with the mutant compared to the wild-type strain (P=0.035). Passive immunization with rabbit polyclonal serum raised against the recombinant N-terminal Esp protein did not protect mice against E. faecium bacteraemia (P>0.05). In contrast, mice passively immunized with polyclonal antiserum raised against lipoteichoic acid (LTA) from E. faecalis had lower numbers of E. faecium E1162 in the blood compared to mice immunized with normal rabbit serum. These results suggest that Esp contributes to E. faecium persistence in the host. However, in contrast to LTA, Esp does not seem to be a target for protective antibodies in E. faecium strain E1162 in mouse bacteraemia.

Trans-sialidase Associated with Atherosclerosis: Defining the Identity of a Key Enzyme Involved in the Pathology

2019 ◽  
Vol 20 (9) ◽  
pp. 938-941
Author(s):  
Victor Y. Glanz ◽  
Veronika A. Myasoedova ◽  
Andrey V. Grechko ◽  
Alexander N. Orekhov
Keyword(s):  
Acid Metabolism ◽  
Research Subject ◽  
Disease Pathogenesis ◽  
Sialidase Activity ◽  
Ph Values ◽  
Ldl Particles ◽  
Optimum Ph ◽  
Key Enzyme ◽  
St6gal I

Atherosclerosis is associated with the increased trans-sialidase activity, which can be detected in the blood plasma of atherosclerosis patients. The likely involvement in the disease pathogenesis made this activity an interesting research subject and the enzyme that may perform such activity was isolated and characterized in terms of substrate specificity and enzymatic properties. It was found that the enzyme has distinct optimum pH values, and its activity was enhanced by the presence of Ca2+ ions. Most importantly, the enzyme was able to cause atherogenic modification of lowdensity lipoprotein (LDL) particles in vitro. However, the identity of the discovered enzyme remained to be defined. Currently, sialyltransferases, mainly ST6Gal I, are regarded as major contributors to sialic acid metabolism in human blood. In this mini-review, we discuss the possibility that atherosclerosis- associated trans-sialidase does, in fact, belong to the sialyltransferases family.

scholarly journals Assessment of Photo-Induced Cytotoxic Activity of Cachrys sicula and Cachrys libanotis Enriched-Coumarin Extracts against Human Melanoma Cells

Plants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 123
Author(s):  
Mariangela Marrelli ◽  
Maria Rosaria Perri ◽  
Valentina Amodeo ◽  
Francesca Giordano ◽  
Giancarlo A. Statti ◽  
...  
Keyword(s):  
Phenolic Content ◽  
Melanoma Cells ◽  
Therapeutic Approaches ◽  
Qualitative And Quantitative ◽  
Aerial Parts ◽  
Naturally Occurring ◽  
Quantitative Analyses ◽  
Solid Liquid ◽  
Uva Radiation

Photochemotherapy is one of the most interesting current therapeutic approaches for the treatment of melanoma. Different classes of naturally occurring phytochemicals demonstrated interesting photoactive properties. The aim of this study was to evaluate the photocytotoxic potential of two Cachrys species from Southern Italy: C. sicula and C. libanotis (Apiaceae). The enriched-coumarin extracts were obtained from aerial parts through both traditional maceration and pressurized cyclic solid-liquid (PCSL) extraction using Naviglio extractor®. Qualitative and quantitative analyses of furanocoumarins were performed with GC-MS. The photocytotoxic effects were verified on C32 melanoma cells irradiated at a dose of 1.08 J/cm2. The apoptotic responses were also assessed. Moreover, phenolic content and the in vitro antioxidant potential were estimated. Xanthotoxin, bergapten, and isopimpinellin were identified. All the samples induced concentration-dependent photocytotoxic effects (IC50 ranging from 3.16 to 18.18 μg/mL). The C. libanotis sample obtained with Naviglio extractor® was the most effective one (IC50 = 3.16 ± 0.21 μg/mL), followed by C. sicula sample obtained with the same technique (IC50 = 8.83 ± 0.20 μg/mL). Both Cachrys samples obtained through PCSL induced up-regulation of apoptotic signals such as BAX (Bcl2-associated X protein) and PARP (poly ADP-ribose polymerase) cleavage. Moreover, these samples proved to be more photoactive, giving a greater upregulation of p21 protein in the presence of UVA radiation. Obtained results suggest that investigated species could be promising candidates for further investigations aimed to find new potential drugs for the photochemotherapy of skin cancer.

scholarly journals Conifers Phytochemicals: A Valuable Forest with Therapeutic Potential

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 3005
Author(s):  
Kanchan Bhardwaj ◽  
Ana Sanches Silva ◽  
Maria Atanassova ◽  
Rohit Sharma ◽  
Eugenie Nepovimova ◽  
...  
Keyword(s):  
Experimental Data ◽  
Potential Role ◽  
Therapeutic Potential ◽  
Fungal Infections ◽  
Cell Damage ◽  
Cancer Growth ◽  
Naturally Occurring ◽  
Antioxidant Effects

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers’ phytochemicals and illustrates their potential role as drugs.

scholarly journals Development and Evaluation of Rifampicin Loaded Alginate–Gelatin Biocomposite Microfibers

Polymers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1514
Author(s):  
Ameya Sharma ◽  
Vivek Puri ◽  
Pradeep Kumar ◽  
Inderbir Singh ◽  
Kampanart Huanbutta
Keyword(s):  
Wound Healing ◽  
Xanthan Gum ◽  
In Vitro Release ◽  
Antimicrobial Properties ◽  
Entrapment Efficiency ◽  
Tissue Proliferation ◽  
Naturally Occurring ◽  
Reinforcing Material ◽  
Vitro Release

Various systematic phases such as inflammation, tissue proliferation, and phases of remodeling characterize the process of wound healing. The natural matrix system is suggested to maintain and escalate these phases, and for that, microfibers were fabricated employing naturally occurring polymers (biopolymers) such as sodium alginate, gelatin and xanthan gum, and reinforcing material such as nanoclay was selected. The fabrication of fibers was executed with the aid of extrusion-gelation method. Rifampicin, an antibiotic, has been incorporated into a biopolymeric solution. RF1, RF2, RF3, RF4 and RF5 were coded as various formulation batches of microfibers. The microfibers were further characterized by different techniques such as SEM, DSC, XRD, and FTIR. Mechanical properties and physical evaluations such as entrapment efficiency, water uptake and in vitro release were also carried out to explain the comparative understanding of the formulation developed. The antimicrobial activity and whole blood clotting of fabricated fibers were additionally executed, hence they showed significant results, having excellent antimicrobial properties; they could be prominent carriers for wound healing applications.

scholarly journals Orodispersible Film Loaded with Enterococcus faecium CRL183 Presents Anti-Candida albicans Biofilm Activity In Vitro

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 998
Author(s):  
Virgínia Barreto Lordello ◽  
Andréia Bagliotti Meneguin ◽  
Sarah Raquel de Annunzio ◽  
Maria Pía Taranto ◽  
Marlus Chorilli ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Enterococcus Faecium ◽  
Potato Starch ◽  
Oral Candidiasis ◽  
Candida Spp ◽  
Sem Images ◽  
Control Film ◽  
In Vitro Antifungal Activity

Background: Probiotic bacteria have been emerging as a trustworthy choice for the prevention and treatment of Candida spp. infections. This study aimed to develop and characterize an orodispersible film (ODF) for delivering the potentially probiotic Enterococcus faecium CRL 183 into the oral cavity, evaluating its in vitro antifungal activity against Candida albicans. Methods and Results: The ODF was composed by carboxymethylcellulose, gelatin, and potato starch, and its physical, chemical, and mechanical properties were studied. The probiotic resistance and viability during processing and storage were evaluated as well as its in vitro antifungal activity against C. albicans. The ODFs were thin, resistant, and flexible, with neutral pH and microbiologically safe. The probiotic resisted the ODF obtaining process, demonstrating high viability (>9 log10 CFU·g−1), up to 90 days of storage at room temperature. The Probiotic Film promoted 68.9% of reduction in fungal early biofilm and 91.2% in its mature biofilm compared to the group stimulated with the control film. Those results were confirmed through SEM images. Conclusion: The probiotic ODF developed is a promising strategy to prevent oral candidiasis, since it permits the local probiotic delivery, which in turn was able to reduce C. albicans biofilm formation.

scholarly journals Expression and prognostic roles of PRDXs gene family in hepatocellular carcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mingxing Xu ◽  
Jianliang Xu ◽  
Dun Zhu ◽  
Rishun Su ◽  
Baoding Zhuang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Acid Metabolism ◽  
Family Members ◽  
Interaction Network ◽  
Genetic Alterations ◽  
Database Analysis ◽  
Kaplan Meier ◽  
Canonical Pathways ◽  
Human Protein Atlas ◽  
Kaplan Meier Plotter

Abstract Background As the fourth leading cause of cancer-related death in the world, the therapeutic effect and 5-year overall survival of hepatocellular carcinoma (HCC) are not optimistic. Previous researches indicated that the disorder of PRDXs was related to the occurrence and development of cancers. Methods In this study, PRDXs were found in various tumor cell lines by CCLE database analysis. The analysis results of UALCAN, HCCDB and Human Protein Atlas databases showed the expression of PRDXs mRNA and protein in HCC tissues was dysregulated. Besides, UALCAN was used to assess the correlations between PRDXs mRNA as well as methylation levels and clinical characterization. Results High expression of PRDX1 or low expression of PRDX2/3 suggested poor prognosis for HCC patients which was demonstrated by Kaplan–Meier Plotter. The genetic alterations and biological interaction network of PRDXs in HCC samples were obtained from c-Bioportal. In addition, LinkedOmics was employed to analyze PRDXs related differentially expressed genes, and on this basis, enrichment of KEGG pathway and miRNAs targets of PRDXs were conducted. The results indicated that these genes were involved in several canonical pathways and certain amino acid metabolism, some of which may effect on the progression of HCC. Conclusions In conclusion, the disordered expression of some PRDX family members was associated with the prognosis of HCC patients, suggesting that these PRDX family members may become new molecular targets for the treatment and prognosis prediction of HCC.

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