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  1. Article ; Online: In Vitro

    Wood, Gwendolyn E / Kim, Caroline M / Aguila, Laarni Kendra T / Cichewicz, Robert H

    Antimicrobial agents and chemotherapy

    2023  Volume 67, Issue 4, Page(s) e0000623

    Abstract: Mycoplasma genitalium is a sexually transmitted reproductive tract pathogen of men and women. M. genitalium infections are increasingly difficult to treat due to poor efficacy of doxycycline and acquired resistance to azithromycin and moxifloxacin. A ... ...

    Abstract Mycoplasma genitalium is a sexually transmitted reproductive tract pathogen of men and women. M. genitalium infections are increasingly difficult to treat due to poor efficacy of doxycycline and acquired resistance to azithromycin and moxifloxacin. A recent clinical trial suggested that metronidazole may improve cure rates for women with pelvic inflammatory disease and reduced the detection of M. genitalium when included with standard doxycycline plus ceftriaxone treatment. As data regarding susceptibility of mycoplasmas to nitroimidazoles are lacking in the scientific literature, we determined the
    MeSH term(s) Male ; Female ; Humans ; Nitroimidazoles/pharmacology ; Nitroimidazoles/therapeutic use ; Doxycycline/pharmacology ; Doxycycline/therapeutic use ; Metronidazole/pharmacology ; Metronidazole/therapeutic use ; Tinidazole/pharmacology ; Tinidazole/therapeutic use ; Mycoplasma genitalium/genetics ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Mycoplasma Infections/drug therapy ; Drug Resistance, Bacterial/genetics
    Chemical Substances Nitroimidazoles ; Doxycycline (N12000U13O) ; secnidazole (R3459K699K) ; Metronidazole (140QMO216E) ; Tinidazole (033KF7V46H) ; Anti-Bacterial Agents
    Language English
    Publishing date 2023-03-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 217602-6
    ISSN 1098-6596 ; 0066-4804
    ISSN (online) 1098-6596
    ISSN 0066-4804
    DOI 10.1128/aac.00006-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Resolving a Natural Product Cold Case: Elucidation of Fusapyrone Structure and Absolute Configuration and Demonstration of Their Fungal Biofilm Disrupting Properties.

    Kil, Yun-Seo / You, Jianlan / Wendt, Karen L / King, Jarrod B / Cichewicz, Robert H

    The Journal of organic chemistry

    2023  Volume 88, Issue 13, Page(s) 9167–9186

    Abstract: Fusapyrones are fungal metabolites, which have been reported to have broad-spectrum antibacterial and antifungal properties. Despite the first members of this chemical class being described three decades prior, many aspects of their structures have ... ...

    Abstract Fusapyrones are fungal metabolites, which have been reported to have broad-spectrum antibacterial and antifungal properties. Despite the first members of this chemical class being described three decades prior, many aspects of their structures have remained unresolved, thereby constraining efforts to fully understand structure-activity relationships within this metabolite family and impeding the design of streamlined syntheses. Among the main challenges posed by fusapyrones is the incorporation of several single and groups of stereocenters separated by atoms with freely rotating bonds, which have proven unyielding to spectroscopic analyses. In this study, we obtained a series of new (
    MeSH term(s) Humans ; Candida albicans ; Antifungal Agents/pharmacology ; Antifungal Agents/chemistry ; Pyrones/pharmacology ; Biofilms
    Chemical Substances fusapyrone (156856-31-4) ; Antifungal Agents ; Pyrones
    Language English
    Publishing date 2023-06-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 123490-0
    ISSN 1520-6904 ; 0022-3263
    ISSN (online) 1520-6904
    ISSN 0022-3263
    DOI 10.1021/acs.joc.3c00765
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Genomic and metabolomic diversity within a familial population of Aspergillus flavus.

    Moore, Geromy G / Mack, Brian M / Wendt, Karen L / Castano-Duque, Lina / Anderson, Victoria M / Cichewicz, Robert H

    Molecular microbiology

    2024  

    Abstract: Aspergillus flavus is an agriculturally significant micro-fungus having potential to contaminate food and feed crops with toxic secondary metabolites such as aflatoxin (AF) and cyclopiazonic acid (CPA). Research has shown A. flavus strains can overcome ... ...

    Abstract Aspergillus flavus is an agriculturally significant micro-fungus having potential to contaminate food and feed crops with toxic secondary metabolites such as aflatoxin (AF) and cyclopiazonic acid (CPA). Research has shown A. flavus strains can overcome heterokaryon incompatibility and undergo meiotic recombination as teleomorphs. Although evidence of recombination in the AF gene cluster has been reported, the impacts of recombination on genotype and metabolomic phenotype in a single generation are lacking. In previous studies, we paired an aflatoxigenic MAT1-1 A. flavus strain with a non-aflatoxigenic MAT1-2 A. flavus strain that had been tagged with green fluorescent protein and then 10 F1 progenies (a mix of fluorescent and non-fluorescent) were randomly selected from single-ascospore colonies and broadly examined for evidence of recombination. In this study, we determined four of those 10 F1 progenies were recombinants because they were not vegetatively compatible with either parent or their siblings, and they exhibited other distinctive traits that could only result from meiotic recombination. The other six progenies examined shared genomic identity with the non-aflatoxigenic, fluorescent, and MAT1-2 parent, but were metabolically distinct. This study highlights phenotypic and genomic changes that may occur in a single generation from the outcrossing of sexually compatible strains of A. flavus.
    Language English
    Publishing date 2024-02-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 619315-8
    ISSN 1365-2958 ; 0950-382X
    ISSN (online) 1365-2958
    ISSN 0950-382X
    DOI 10.1111/mmi.15244
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  4. Article ; Online: Persephacin Is a Broad-Spectrum Antifungal Aureobasidin Metabolite That Overcomes Intrinsic Resistance in

    Du, Lin / Haldar, Saikat / King, Jarrod B / Mattes, Allison O / Srivastava, Shikha / Wendt, Karen L / You, Jianlan / Cunningham, Chad / Cichewicz, Robert H

    Journal of natural products

    2023  Volume 86, Issue 8, Page(s) 1980–1993

    Abstract: Fungi pose a persistent threat to humankind with worrying indications that emerging and re-emerging pathogens (e.g., ...

    Abstract Fungi pose a persistent threat to humankind with worrying indications that emerging and re-emerging pathogens (e.g.,
    MeSH term(s) Animals ; Humans ; Antifungal Agents/pharmacology ; Fluconazole/pharmacology ; Aspergillus fumigatus ; Microbial Sensitivity Tests ; Candida albicans
    Chemical Substances Antifungal Agents ; Fluconazole (8VZV102JFY)
    Language English
    Publishing date 2023-07-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 304325-3
    ISSN 1520-6025 ; 0163-3864
    ISSN (online) 1520-6025
    ISSN 0163-3864
    DOI 10.1021/acs.jnatprod.3c00382
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  5. Article ; Online: Identification of fungal natural products with potent inhibition in

    Jiang, Tiantian / Godinez-Macias, Karla P / Collins, Jennifer E / Lee, Jin Woo / Wendt, Karen L / Carolino, Krypton / Chakrabarti, Debopam / Cichewicz, Robert H / Winzeler, Elizabeth A

    Microbiology spectrum

    2024  Volume 12, Issue 4, Page(s) e0414223

    Abstract: In an effort to identify novel compounds with potent inhibition against : Importance: Current therapeutics for treating toxoplasmosis remain insufficient, demonstrating high cytotoxicity, poor bioavailability, limited efficacy, and drug resistance. ... ...

    Abstract In an effort to identify novel compounds with potent inhibition against
    Importance: Current therapeutics for treating toxoplasmosis remain insufficient, demonstrating high cytotoxicity, poor bioavailability, limited efficacy, and drug resistance. Additional research is needed to develop novel compounds with high efficacy and low cytotoxicity. The success of artemisinin and other natural products in treating malaria highlights the potential of natural products as anti-protozoan therapeutics. However, the exploration of natural products in
    MeSH term(s) Humans ; Toxoplasma ; Antiprotozoal Agents/pharmacology ; Biological Products/pharmacology ; Toxoplasmosis ; Malaria ; Artemisinins/pharmacology
    Chemical Substances Antiprotozoal Agents ; Biological Products ; Artemisinins
    Language English
    Publishing date 2024-02-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2807133-5
    ISSN 2165-0497 ; 2165-0497
    ISSN (online) 2165-0497
    ISSN 2165-0497
    DOI 10.1128/spectrum.04142-23
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  6. Article: Correction for Anderson et al., "Building Natural Product Libraries Using Quantitative Clade-Based and Chemical Clustering Strategies".

    Anderson, Victoria M / Wendt, Karen L / Najar, Fares Z / McCall, Laura-Isobel / Cichewicz, Robert H

    mSystems

    2021  Volume 6, Issue 6, Page(s) e0141821

    Language English
    Publishing date 2021-12-14
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ISSN 2379-5077
    ISSN 2379-5077
    DOI 10.1128/msystems.01418-21
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  7. Article ; Online: Leveraging Peptaibol Biosynthetic Promiscuity for Next-Generation Antiplasmodial Therapeutics.

    Lee, Jin Woo / Collins, Jennifer E / Wendt, Karen L / Chakrabarti, Debopam / Cichewicz, Robert H

    Journal of natural products

    2021  Volume 84, Issue 2, Page(s) 503–517

    Abstract: Malaria remains a worldwide threat, afflicting over 200 million people each year. The emergence of drug resistance against existing therapeutics threatens to destabilize global efforts aimed at ... ...

    Abstract Malaria remains a worldwide threat, afflicting over 200 million people each year. The emergence of drug resistance against existing therapeutics threatens to destabilize global efforts aimed at controlling
    MeSH term(s) Antimalarials/pharmacology ; Biological Products/pharmacology ; Drug Resistance ; Hep G2 Cells ; Humans ; Hypocrea/chemistry ; Molecular Structure ; Pennsylvania ; Peptaibols/biosynthesis ; Peptaibols/pharmacology ; Plasmodium falciparum/drug effects ; Soil Microbiology ; Texas ; Trichoderma/chemistry
    Chemical Substances Antimalarials ; Biological Products ; Peptaibols
    Language English
    Publishing date 2021-02-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 304325-3
    ISSN 1520-6025 ; 0163-3864
    ISSN (online) 1520-6025
    ISSN 0163-3864
    DOI 10.1021/acs.jnatprod.0c01370
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  8. Article: Building Natural Product Libraries Using Quantitative Clade-Based and Chemical Clustering Strategies.

    Anderson, Victoria M / Wendt, Karen L / Najar, Fares Z / McCall, Laura-Isobel / Cichewicz, Robert H

    mSystems

    2021  Volume 6, Issue 5, Page(s) e0064421

    Abstract: The success of natural product-based drug discovery is predicated on having chemical collections that offer broad coverage of metabolite diversity. We propose a simple set of tools combining genetic barcoding and metabolomics to help investigators build ... ...

    Abstract The success of natural product-based drug discovery is predicated on having chemical collections that offer broad coverage of metabolite diversity. We propose a simple set of tools combining genetic barcoding and metabolomics to help investigators build natural product libraries aimed at achieving predetermined levels of chemical coverage. It was found that such tools aided in identifying overlooked pockets of chemical diversity within taxa, which could be useful for refocusing collection strategies. We have used fungal isolates identified as
    Language English
    Publishing date 2021-10-26
    Publishing country United States
    Document type Journal Article
    ISSN 2379-5077
    ISSN 2379-5077
    DOI 10.1128/mSystems.00644-21
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  9. Article ; Online: Appraisal of Fungus-Derived Xanthoquinodins as Broad-Spectrum Anti-Infectives Targeting Phylogenetically Diverse Human Pathogens.

    Lee, Jin Woo / Collins, Jennifer E / Hulverson, Matthew A / Aguila, Laarni Kendra T / Kim, Caroline M / Wendt, Karen L / Chakrabarti, Debopam / Ojo, Kayode K / Wood, Gwendolyn E / Van Voorhis, Wesley C / Cichewicz, Robert H

    Journal of natural products

    2023  Volume 86, Issue 6, Page(s) 1596–1605

    Abstract: Xanthoquinodins make up a distinctive class of xanthone-anthraquinone heterodimers reported as secondary metabolites from several fungal species. Through a collaborative multi-institutional screening program, a fungal extract prepared from ... ...

    Abstract Xanthoquinodins make up a distinctive class of xanthone-anthraquinone heterodimers reported as secondary metabolites from several fungal species. Through a collaborative multi-institutional screening program, a fungal extract prepared from a
    MeSH term(s) Humans ; Cryptosporidiosis ; Cryptosporidium ; Anti-Infective Agents/pharmacology ; Mitosporic Fungi ; Anti-Bacterial Agents/pharmacology ; Molecular Structure
    Chemical Substances Anti-Infective Agents ; Anti-Bacterial Agents
    Language English
    Publishing date 2023-06-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 304325-3
    ISSN 1520-6025 ; 0163-3864
    ISSN (online) 1520-6025
    ISSN 0163-3864
    DOI 10.1021/acs.jnatprod.3c00283
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  10. Article ; Online: Identification of Fungus-Derived Natural Products as New Antigiardial Scaffolds.

    Hulverson, Matthew A / Michaels, Samantha A / Lee, Jin Woo / Wendt, Karen L / Tran, Linh T / Choi, Ryan / Van Voorhis, Wesley C / Cichewicz, Robert H / Ojo, Kayode K

    Microbiology spectrum

    2023  Volume 11, Issue 3, Page(s) e0064723

    Abstract: There is an unmet need for effective therapies for treating diseases associated with the intestinal parasite Giardia lamblia. In this study, a library of chemically validated purified natural products and fungal extracts was screened for chemical ... ...

    Abstract There is an unmet need for effective therapies for treating diseases associated with the intestinal parasite Giardia lamblia. In this study, a library of chemically validated purified natural products and fungal extracts was screened for chemical scaffolds that can inhibit the growth of G. lamblia. The phenotypic screen led to the identification of several previously unreported classes of natural product inhibitors that block the growth of G. lamblia. Hits from phenotypic screens of these naturally derived compounds are likely to possess a variety of mechanisms of action not associated with clinically used nitroimidazole and thiazolide compounds. They may therefore be effective against current drug-resistant parasite strains.
    MeSH term(s) Child ; Humans ; Giardiasis/parasitology ; Antiprotozoal Agents/pharmacology ; Biological Products/pharmacology ; Metronidazole/therapeutic use ; Fungi
    Chemical Substances Antiprotozoal Agents ; Biological Products ; Metronidazole (140QMO216E)
    Language English
    Publishing date 2023-04-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2807133-5
    ISSN 2165-0497 ; 2165-0497
    ISSN (online) 2165-0497
    ISSN 2165-0497
    DOI 10.1128/spectrum.00647-23
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