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Book ; Online ; E-Book: Jawetz, Melnick & Adelberg's medical microbiology

Riedel, Stefan / Hobden, Jeffery A. / Miller, Steve / Morse, Stephen A. / Mietzner, Timothy A. / Detrick, Barbara / Mitchell, Thomas G. / McKerrow, J. H. / Sakanari, Judy A. / Hotez, Peter / Mejia, Rojelio

2019

Author's details	Stefan Reidel, Jeffrey A. Hobden, Steve Miller, Stephen A. Morse, Timothy A. Mietzner, Barbara Detrick. Thomas G. Mitchell, Judy A. Sakanari, Peter Hotez, Rojelio Mejia
Keywords	Medical microbiology ; Diagnostic microbiology
Language	English
Size	1 online resource (x, 867 pages) :, illustrations (chiefly colour)
Edition	28th edition.
Publisher	McGraw-Hill Education
Publishing place	New York
Document type	Book ; Online ; E-Book
Note	Previous edition 2016. ; "A Lange medical book."
Remark	Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
ISBN	9781260012026 ; 1260012026
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Drugs that target early stages of Onchocerca volvulus: A revisited means to facilitate the elimination goals for onchocerciasis.

Jawahar, Shabnam / Tricoche, Nancy / Bulman, Christina A / Sakanari, Judy / Lustigman, Sara

PLoS neglected tropical diseases

2021 Volume 15, Issue 2, Page(s) e0009064

Abstract: Several issues have been identified with the current programs for the elimination of onchocerciasis that target only transmission by using mass drug administration (MDA) of the drug ivermectin. Alternative and/or complementary treatment regimens as part ... ...

Abstract	Several issues have been identified with the current programs for the elimination of onchocerciasis that target only transmission by using mass drug administration (MDA) of the drug ivermectin. Alternative and/or complementary treatment regimens as part of a more comprehensive strategy to eliminate onchocerciasis are needed. We posit that the addition of "prophylactic" drugs or therapeutic drugs that can be utilized in a prophylactic strategy to the toolbox of present microfilaricidal drugs and/or future macrofilaricidal treatment regimens will not only improve the chances of meeting the elimination goals but may hasten the time to elimination and also will support achieving a sustained elimination of onchocerciasis. These "prophylactic" drugs will target the infective third- (L3) and fourth-stage (L4) larvae of Onchocerca volvulus and consequently prevent the establishment of new infections not only in uninfected individuals but also in already infected individuals and thus reduce the overall adult worm burden and transmission. Importantly, an effective prophylactic treatment regimen can utilize drugs that are already part of the onchocerciasis elimination program (ivermectin), those being considered for MDA (moxidectin), and/or the potential macrofilaricidal drugs (oxfendazole and emodepside) currently under clinical development. Prophylaxis of onchocerciasis is not a new concept. We present new data showing that these drugs can inhibit L3 molting and/or inhibit motility of L4 at IC50 and IC90 that are covered by the concentration of these drugs in plasma based on the corresponding pharmacological profiles obtained in human clinical trials when these drugs were tested using various doses for the therapeutic treatments of various helminth infections.
MeSH term(s)	Animals ; Benzimidazoles/pharmacology ; Depsipeptides/pharmacology ; Filaricides/pharmacology ; Humans ; Ivermectin/pharmacology ; Larva/drug effects ; Leukocytes, Mononuclear/parasitology ; Macrolides/pharmacology ; Onchocerca volvulus/drug effects ; Onchocerca volvulus/growth & development ; Onchocerciasis/drug therapy ; Onchocerciasis/prevention & control
Chemical Substances	Benzimidazoles ; Depsipeptides ; Filaricides ; Macrolides ; Ivermectin (70288-86-7) ; moxidectin (NGU5H31YO9) ; oxfendazole (OMP2H17F9E) ; emodepside (YZ647Y5GC9)
Language	English
Publishing date	2021-02-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2727
ISSN (online)	1935-2735
ISSN	1935-2727
DOI	10.1371/journal.pntd.0009064
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Combinations of the azaquinazoline anti-

Frontiers in microbiology

2024 Volume 15, Page(s) 1346068

Abstract: Lymphatic filariasis and onchocerciasis are two major neglected tropical diseases that are responsible for causing severe disability in 50 million people worldwide, whilst veterinary filariasis (heartworm) is a potentially lethal parasitic infection of ... ...

Abstract	Lymphatic filariasis and onchocerciasis are two major neglected tropical diseases that are responsible for causing severe disability in 50 million people worldwide, whilst veterinary filariasis (heartworm) is a potentially lethal parasitic infection of companion animals. There is an urgent need for safe, short-course curative (macrofilaricidal) drugs to eliminate these debilitating parasite infections. We investigated combination treatments of the novel anti-
Language	English
Publishing date	2024-02-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2024.1346068
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Article ; Online: Uncovering the essential roles of glutamate carboxypeptidase 2 orthologs in Caenorhabditis elegans.

Panska, Lucie / Nedvedova, Stepanka / Vacek, Vojtech / Krivska, Daniela / Konecny, Lukas / Knop, Filip / Kutil, Zsofia / Skultetyova, Lubica / Leontovyc, Adrian / Ulrychova, Lenka / Sakanari, Judy / Asahina, Masako / Barinka, Cyril / Macurkova, Marie / Dvorak, Jan

Bioscience reports

2023 Volume 44, Issue 1

Abstract: Human glutamate carboxypeptidase 2 (GCP2) from the M28B metalloprotease group is an important target for therapy in neurological disorders and an established tumor marker. However, its physiological functions remain unclear. To better understand general ... ...

Abstract	Human glutamate carboxypeptidase 2 (GCP2) from the M28B metalloprotease group is an important target for therapy in neurological disorders and an established tumor marker. However, its physiological functions remain unclear. To better understand general roles, we used the model organism Caenorhabditis elegans to genetically manipulate its three existing orthologous genes and evaluate the impact on worm physiology. The results of gene knockout studies showed that C. elegans GCP2 orthologs affect the pharyngeal physiology, reproduction, and structural integrity of the organism. Promoter-driven GFP expression revealed distinct localization for each of the three gene paralogs, with gcp-2.1 being most abundant in muscles, intestine, and pharyngeal interneurons, gcp-2.2 restricted to the phasmid neurons, and gcp-2.3 located in the excretory cell. The present study provides new insight into the unique phenotypic effects of GCP2 gene knockouts in C. elegans, and the specific tissue localizations. We believe that elucidation of particular roles in a non-mammalian organism can help to explain important questions linked to physiology of this protease group and in extension to human GCP2 involvement in pathophysiological processes.
MeSH term(s)	Animals ; Humans ; Caenorhabditis elegans/genetics ; Carboxypeptidases/genetics ; Carboxypeptidases/metabolism ; Promoter Regions, Genetic ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism
Chemical Substances	glutamate carboxypeptidase (EC 3.4.17.11) ; Carboxypeptidases (EC 3.4.-) ; Caenorhabditis elegans Proteins
Language	English
Publishing date	2023-12-18
Publishing country	England
Document type	Journal Article
ZDB-ID	764946-0
ISSN	1573-4935 ; 0144-8463
ISSN (online)	1573-4935
ISSN	0144-8463
DOI	10.1042/BSR20230502
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Article ; Online: Biochemical and structural characterizations of thioredoxin reductase selenoproteins of the parasitic filarial nematodes Brugia malayi and Onchocerca volvulus.

Fata, Francesca / Gencheva, Radosveta / Cheng, Qing / Lullo, Rachel / Ardini, Matteo / Silvestri, Ilaria / Gabriele, Federica / Ippoliti, Rodolfo / Bulman, Christina A / Sakanari, Judy A / Williams, David L / Arnér, Elias S J / Angelucci, Francesco

Redox biology

2022 Volume 51, Page(s) 102278

Abstract: Enzymes in the thiol redox systems of microbial pathogens are promising targets for drug development. In this study we characterized the thioredoxin reductase (TrxR) selenoproteins from Brugia malayi and Onchocerca volvulus, filarial nematode parasites ... ...

Abstract	Enzymes in the thiol redox systems of microbial pathogens are promising targets for drug development. In this study we characterized the thioredoxin reductase (TrxR) selenoproteins from Brugia malayi and Onchocerca volvulus, filarial nematode parasites and causative agents of lymphatic filariasis and onchocerciasis, respectively. The two filarial enzymes showed similar turnover numbers and affinities for different thioredoxin (Trx) proteins, but with a clear preference for the autologous Trx. Human TrxR1 (hTrxR1) had a high and similar specific activity versus the human and filarial Trxs, suggesting that, in vivo, hTrxR1 could possibly be the reducing agent of parasite Trxs once they are released into the host. Both filarial TrxRs were efficiently inhibited by auranofin and by a recently described inhibitor of human TrxR1 (TRi-1), but not as efficiently by the alternative compound TRi-2. The enzyme from B. malayi was structurally characterized also in complex with NADPH and auranofin, producing the first crystallographic structure of a nematode TrxR. The protein represents an unusual fusion of a mammalian-type TrxR protein architecture with an N-terminal glutaredoxin-like (Grx) domain lacking typical Grx motifs. Unlike thioredoxin glutathione reductases (TGRs) found in platyhelminths and mammals, which are also Grx-TrxR domain fusion proteins, the TrxRs from the filarial nematodes lacked glutathione disulfide reductase and Grx activities. The structural determinations revealed that the Grx domain of TrxR from B. malayi contains a cysteine (C22), conserved in TrxRs from clade IIIc nematodes, that directly interacts with the C-terminal cysteine-selenocysteine motif of the homo-dimeric subunit. Interestingly, despite this finding we found that altering C22 by mutation to serine did not affect enzyme catalysis. Thus, although the function of the Grx domain in these filarial TrxRs remains to be determined, the results obtained provide insights on key properties of this important family of selenoprotein flavoenzymes that are potential drug targets for treatment of filariasis.
MeSH term(s)	Animals ; Auranofin/pharmacology ; Brugia malayi/metabolism ; Cysteine/metabolism ; Humans ; Mammals/metabolism ; Onchocerca volvulus/genetics ; Onchocerca volvulus/metabolism ; Oxidation-Reduction ; Parasites/metabolism ; Selenoproteins/genetics ; Selenoproteins/metabolism ; Thioredoxin-Disulfide Reductase/genetics ; Thioredoxin-Disulfide Reductase/metabolism ; Thioredoxins/genetics ; Thioredoxins/metabolism
Chemical Substances	Selenoproteins ; Auranofin (3H04W2810V) ; Thioredoxins (52500-60-4) ; Thioredoxin-Disulfide Reductase (EC 1.8.1.9) ; Cysteine (K848JZ4886)
Language	English
Publishing date	2022-03-04
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2701011-9
ISSN	2213-2317 ; 2213-2317
ISSN (online)	2213-2317
ISSN	2213-2317
DOI	10.1016/j.redox.2022.102278
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Article: Anisakis - from the platter to the microfuge.

Sakanari, J A

Parasitology today (Personal ed.)

2004 Volume 6, Issue 10, Page(s) 323–327

Abstract: ... produce lesions characterized by a marked inflammatory response. Judy Sakanari describes the biochemical ...

Abstract	Anisakiasis is a disease caused by the ingestion of anisakid nematodes in raw or improperly prepared fish dishes. Invading larvae penetrate the mucosa and submucosa of the gastrointestinal tract and produce lesions characterized by a marked inflammatory response. Judy Sakanari describes the biochemical and molecular studies on the proteins excreted and/or secreted by Anisakis larvae that are currently underway to help elucidate the role these proteins may play in the invasion process and the pathogenesis of anisakiasis.
Language	English
Publishing date	2004-09-10
Publishing country	England
Document type	Journal Article
ZDB-ID	632787-4
ISSN	0169-4758
ISSN	0169-4758
DOI	10.1016/0169-4758(90)90176-5
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Article ; Online: De novo identification of toxicants that cause irreparable damage to parasitic nematode intestinal cells.

Jasmer, Douglas P / Rosa, Bruce A / Tyagi, Rahul / Bulman, Christina A / Beerntsen, Brenda / Urban, Joseph F / Sakanari, Judy / Mitreva, Makedonka

PLoS neglected tropical diseases

2020 Volume 14, Issue 5, Page(s) e0007942

Abstract: Efforts to identify new drugs for therapeutic and preventive treatments against parasitic nematodes have gained increasing interest with expanding pathogen omics databases and drug databases from which new anthelmintic compounds might be identified. Here, ...

Abstract	Efforts to identify new drugs for therapeutic and preventive treatments against parasitic nematodes have gained increasing interest with expanding pathogen omics databases and drug databases from which new anthelmintic compounds might be identified. Here, a novel approach focused on integrating a pan-Nematoda multi-omics data targeted to a specific nematode organ system (the intestinal tract) with evidence-based filtering and chemogenomic screening was undertaken. Based on de novo computational target prioritization of the 3,564 conserved intestine genes in A. suum, exocytosis was identified as a high priority pathway, and predicted inhibitors of exocytosis were tested using the large roundworm (Ascaris suum larval stages), a filarial worm (Brugia pahangi adult and L3), a whipworm (Trichuris muris adult), and the non-parasitic nematode Caenorhabditis elegans. 10 of 13 inhibitors were found to cause rapid immotility in A. suum L3 larvae, and five inhibitors were effective against the three phylogenetically diverse parasitic nematode species, indicating potential for a broad spectrum anthelmintics. Several distinct pathologic phenotypes were resolved related to molting, motility, or intestinal cell and tissue damage using conventional and novel histologic methods. Pathologic profiles characteristic for each inhibitor will guide future research to uncover mechanisms of the anthelmintic effects and improve on drug designs. This progress firmly validates the focus on intestinal cell biology as a useful resource to develop novel anthelmintic strategies.
MeSH term(s)	Animals ; Anthelmintics/pharmacology ; Cells, Cultured ; Drug Delivery Systems ; Drug Discovery ; Intestines/cytology ; Intestines/drug effects ; Larva/drug effects ; Nematoda/drug effects
Chemical Substances	Anthelmintics
Language	English
Publishing date	2020-05-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2727
ISSN (online)	1935-2735
ISSN	1935-2727
DOI	10.1371/journal.pntd.0007942
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Article ; Online: Filaricidal activity of Daniellia oliveri and Psorospermum febrifugum extracts.

Abongwa, Melanie / Samje, Moses / Ayimele, Godfred A / Babiaka, Smith B / Bulman, Christina / Sakanari, Judy / Koszewski, Nick J / Verma, Saurabh / Goff, Jesse / Cho-Ngwa, Fidelis / Martin, Richard J / Robertson, Alan P

Parasites & vectors

2021 Volume 14, Issue 1, Page(s) 305

Abstract: Background: Drugs currently used for controlling onchocerciasis and lymphatic filariasis (LF) are mainly microfilaricidal, with minimal or no effect on the adult worms. For efficient management of these diseases, it is necessary to search for new drugs ... ...

Abstract	Background: Drugs currently used for controlling onchocerciasis and lymphatic filariasis (LF) are mainly microfilaricidal, with minimal or no effect on the adult worms. For efficient management of these diseases, it is necessary to search for new drugs with macrofilaricidal activities that can be used singly or in combination with existing ones. Daniellia oliveri and Psorospermum febrifugum are two plants commonly used in the local management of these infections in Bambui, a township in the North West Region of Cameroon, but there is currently no documented scientific evidence to support their claimed anthelmintic efficacy and safety. The aim of this study was to provide evidence in support of the search for means to eliminate these diseases by screening extracts and chromatographic fractions isolated from these plants for efficacy against the parasitic roundworms Onchocerca ochengi and Brugia pahangi. Methods: The viability of O. ochengi adult worms was assessed using the MTT/formazan assay. Fully confluent monkey kidney epithelial cells (LLC-MK2) served as the feeder layer for the O. ochengi microfilariae (mfs) assays. Viability of the mfs was assessed by microscopic examination for mean motility scoring (relative to the negative control) every 24 h post addition of an extract. The Worminator system was used to test the effects of the extracts on adult B. pahangi motility, and mean motility units were determined for each worm. Cytotoxicity of the active extracts on N27 cells was assessed using the MTS assay. Results: Extracts from D. oliveri and P. febrifugum were effective against the adult roundworms O. ochengi and B. pahangi. Interestingly, extracts showing macrofilaricidal activities against O. ochengi also showed activity against O. ochengi mfs. The hexane stem bark extract of D. oliveri (DO Conclusions: Our study supports the use of D. oliveri and P. febrifugum in the traditional treatment of onchocerciasis and LF. The further purification of active extracts from these plants could yield lead compounds for filarial drug discovery and development.
MeSH term(s)	Animals ; Cameroon ; Cell Line ; Clusiaceae/chemistry ; Fabaceae/chemistry ; Filaricides/pharmacology ; Haplorhini ; Humans ; Onchocerca/drug effects ; Onchocerca/growth & development ; Onchocerciasis/drug therapy ; Onchocerciasis/parasitology ; Plant Bark/chemistry ; Plant Extracts/pharmacology
Chemical Substances	Filaricides ; Plant Extracts
Language	English
Publishing date	2021-06-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2409480-8
ISSN	1756-3305 ; 1756-3305
ISSN (online)	1756-3305
ISSN	1756-3305
DOI	10.1186/s13071-021-04759-6
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Article: Discovery of New Broad-Spectrum Anti-Infectives for Eukaryotic Pathogens Using Bioorganometallic Chemistry.

bioRxiv : the preprint server for biology

2023

Abstract: Drug resistance observed with many anti-infectives clearly highlights the need for new broad-spectrum agents to treat especially neglected tropical diseases (NTDs) caused by eukaryotic parasitic pathogens including fungal infections. Since these diseases ...

Abstract	Drug resistance observed with many anti-infectives clearly highlights the need for new broad-spectrum agents to treat especially neglected tropical diseases (NTDs) caused by eukaryotic parasitic pathogens including fungal infections. Since these diseases target the most vulnerable communities who are disadvantaged by health and socio-economic factors, new agents should be, if possible, easy-to-prepare to allow for commercialization based on their low cost. In this study, we show that simple modification of one of the most well-known antifungal drugs, fluconazole, with organometallic moieties not only improves the activity of the parent drug but also broadens the scope of application of the new derivatives. These compounds were highly effective One-sentence summary: Simple derivatives of the well-known antifungal drug fluconazole were found to be highly effective
Language	English
Publishing date	2023-06-30
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.06.28.546819
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Article ; Online: Discovery of New Broad-Spectrum Anti-Infectives for Eukaryotic Pathogens Using Bioorganometallic Chemistry.

Journal of medicinal chemistry

2023 Volume 66, Issue 23, Page(s) 15867–15882

Abstract: Drug resistance observed with many anti-infectives clearly highlights the need for new broad-spectrum agents to treat especially neglected tropical diseases (NTDs) caused by eukaryotic parasitic pathogens, including fungal infections. Herein, we show ... ...

Abstract	Drug resistance observed with many anti-infectives clearly highlights the need for new broad-spectrum agents to treat especially neglected tropical diseases (NTDs) caused by eukaryotic parasitic pathogens, including fungal infections. Herein, we show that the simple modification of one of the most well-known antifungal drugs, fluconazole, with organometallic moieties not only improves the activity of the parent drug but also broadens the scope of application of the new derivatives. These compounds were highly effective in vivo against pathogenic fungal infections and potent against parasitic worms such as
MeSH term(s)	Humans ; Antifungal Agents/pharmacology ; Antifungal Agents/therapeutic use ; Neglected Diseases/drug therapy ; Fluconazole ; Mycoses/drug therapy
Chemical Substances	Antifungal Agents ; Fluconazole (8VZV102JFY)
Language	English
Publishing date	2023-11-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.3c01333
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