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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: Intramolecular Interactions Enhance the Potency of Gallinamide A Analogues against

Barbosa Da Silva, Elany / Sharma, Vandna / Hernandez-Alvarez, Lilian / Tang, Arthur H / Stoye, Alexander / O'Donoghue, Anthony J / Gerwick, William H / Payne, Richard J / McKerrow, James H / Podust, Larissa M

Journal of medicinal chemistry

2022 Volume 65, Issue 5, Page(s) 4255–4269

Abstract: Gallinamide A, a metabolite of the marine ... ...

Abstract	Gallinamide A, a metabolite of the marine cyanobacterium
MeSH term(s)	Antimicrobial Cationic Peptides/chemistry ; Cysteine Proteases ; Cysteine Proteinase Inhibitors/chemistry ; Cysteine Proteinase Inhibitors/pharmacology ; Protozoan Proteins ; Trypanosoma cruzi
Chemical Substances	Antimicrobial Cationic Peptides ; Cysteine Proteinase Inhibitors ; Protozoan Proteins ; gallinamide A ; Cysteine Proteases (EC 3.4.-)
Language	English
Publishing date	2022-02-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.1c02063
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Article: Discovery of Triple Inhibitors of Both SARS-CoV-2 Proteases and Human Cathepsin L.

Meewan, Ittipat / Kattoula, Jacob / Kattoula, Julius Y / Skinner, Danielle / Fajtová, Pavla / Giardini, Miriam A / Woodworth, Brendon / McKerrow, James H / Lage de Siqueira-Neto, Jair / O'Donoghue, Anthony J / Abagyan, Ruben

Pharmaceuticals (Basel, Switzerland)

2022 Volume 15, Issue 6

Abstract: One inhibitor of the main SARS-CoV-2 protease has been approved recently by the FDA, yet it targets only SARS-CoV-2 main protease (Mpro). Here, we discovered inhibitors containing thiuram disulfide or dithiobis-(thioformate) tested ... ...

Abstract	One inhibitor of the main SARS-CoV-2 protease has been approved recently by the FDA, yet it targets only SARS-CoV-2 main protease (Mpro). Here, we discovered inhibitors containing thiuram disulfide or dithiobis-(thioformate) tested against
Language	English
Publishing date	2022-06-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph15060744
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Article ; Online: Affinity-Based Interactome Analysis of Endogenous LINE-1 Macromolecules.

Di Stefano, Luciano H / Saba, Leila J / Oghbaie, Mehrnoosh / Jiang, Hua / McKerrow, Wilson / Benitez-Guijarro, Maria / Taylor, Martin S / LaCava, John

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2607, Page(s) 215–256

Abstract: During their proliferation and the host's concomitant attempts to suppress it, LINE-1 (L1) retrotransposons give rise to a collection of heterogeneous ribonucleoproteins (RNPs); their protein and RNA compositions remain poorly defined. The constituents ... ...

Abstract	During their proliferation and the host's concomitant attempts to suppress it, LINE-1 (L1) retrotransposons give rise to a collection of heterogeneous ribonucleoproteins (RNPs); their protein and RNA compositions remain poorly defined. The constituents of L1-associated macromolecules can differ depending on numerous factors, including, for example, position within the L1 life cycle, whether the macromolecule is productive or under suppression, and the cell type within which the proliferation is occurring. This chapter describes techniques that aid the capture and characterization of protein and RNA components of L1 macromolecules from tissues that natively express them. The protocols described have been applied to embryonal carcinoma cell lines that are popular model systems for L1 molecular biology (e.g., N2102Ep, NTERA-2, and PA-1 cells), as well as colorectal cancer tissues. N2102Ep cells are given as the use case for this chapter; the protocols should be applicable to essentially any tissue exhibiting endogenous L1 expression with minor modifications.
MeSH term(s)	Long Interspersed Nucleotide Elements ; Macromolecular Substances ; Retroelements ; Embryonal Carcinoma Stem Cells ; RNA
Chemical Substances	Macromolecular Substances ; Retroelements ; RNA (63231-63-0)
Language	English
Publishing date	2022-11-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2883-6_12
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Article ; Online: Molecular dissection of Chagas induced cardiomyopathy reveals central disease associated and druggable signaling pathways.

Wozniak, Jacob M / Silva, Tatiana Araújo / Thomas, Diane / Siqueira-Neto, Jair L / McKerrow, James H / Gonzalez, David J / Calvet, Claudia M

PLoS neglected tropical diseases

2020 Volume 14, Issue 5, Page(s) e0007980

Abstract: Chagas disease, the clinical presentation of T. cruzi infection, is a major human health concern. While the acute phase of Chagas disease is typically asymptomatic and self-resolving, chronically infected individuals suffer numerous sequelae later in ... ...

Abstract	Chagas disease, the clinical presentation of T. cruzi infection, is a major human health concern. While the acute phase of Chagas disease is typically asymptomatic and self-resolving, chronically infected individuals suffer numerous sequelae later in life. Cardiomyopathies in particular are the most severe consequence of chronic Chagas disease and cannot be reversed solely by parasite load reduction. To prioritize new therapeutic targets, we unbiasedly interrogated the host signaling events in heart tissues isolated from a Chagas disease mouse model using quantitative, multiplexed proteomics. We defined the host response to infection at both the proteome and phospho-proteome levels. The proteome showed an increase in the immune response and a strong repression of several mitochondrial proteins. Complementing the proteome studies, the phospho-proteomic survey found an abundance of phospho-site alterations in plasma membrane and cytoskeletal proteins. Bioinformatic analysis of kinase activity provided substantial evidence for the activation of NDRG2 and JNK/p38 kinases during Chagas disease. A significant activation of DYRK2 and AMPKA2 and the inhibition of casein family kinases were also predicted. We concluded our analyses by linking the diseased heart proteome profile to known therapeutic interventions, uncovering a potential to target mitochondrial proteins, secreted immune effectors and core kinases for the treatment of chronic Chagas disease. Together, this study provides molecular insight into host proteome and phospho-proteome responses to T. cruzi infection in the heart for the first time, highlighting pathways that can be further validated for functional contributions to disease and suitability as drug targets.
MeSH term(s)	Animals ; Chagas Cardiomyopathy/genetics ; Chagas Cardiomyopathy/immunology ; Chagas Cardiomyopathy/metabolism ; Chagas Cardiomyopathy/parasitology ; Female ; Humans ; Mice ; Mice, Inbred C57BL ; Proteome/genetics ; Proteome/metabolism ; Proteomics ; Signal Transduction ; Trypanosoma cruzi/physiology
Chemical Substances	Proteome
Language	English
Publishing date	2020-05-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; 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.0007980
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Article ; Online: Predictions of novel Schistosoma mansoni - human protein interactions consistent with experimental data.

White Bear, J / Long, Thavy / Skinner, Danielle / McKerrow, James H

Scientific reports

2018 Volume 8, Issue 1, Page(s) 13092

Abstract: Infection by the human blood fluke, Schistosoma mansoni involves a variety of cross-species protein- protein interactions. The pathogen expresses a diverse arsenal of proteins that facilitate the breach of physical and biochemical barriers present in ... ...

Abstract	Infection by the human blood fluke, Schistosoma mansoni involves a variety of cross-species protein- protein interactions. The pathogen expresses a diverse arsenal of proteins that facilitate the breach of physical and biochemical barriers present in skin evasion of the immune system, and digestion of human plasma proteins including albumin and hemoglobin, allowing schistosomes to reside in the host for years. However, only a small number of specific interactions between S. mansoni and human proteins have been identified. We present and apply a protocol that generates testable predictions of S. mansoni-human protein interactions. In this study, we have preliminary predictions of novel interactions between schistosome and human proteins relevant to infection and the ability of the parasite to evade the immune system. We applied a computational whole-genome comparative approach to predict potential S. mansoni-human protein interactions based on similarity to known protein complexes. We first predict S. mansoni -human protein interactions based on similarity to known protein complexes. Putative interactions were then scored and assessed using several contextual filters, including the use of annotation automatically derived from literature using a simple natural language processing methodology. Next, in vitro experiments were carried out between schistosome and host proteins to validate several prospective predictions. Our method predicted 7 out of the 10 previously known cross-species interactions involved in pathogenesis between S. mansoni and its human host. Interestingly, two novel putative interactions involving Schistosoma proteins, the cercarial elastase SmCE, and the adult tegument surface protein Sm29, were also predicted and experimentally characterized. Preliminary data suggest that elafin, a host endogenous serine protease inhibitor, may be a novel substrate for SmCE. Additionally, CD59, an inhibitor of the membrane attack complex, could interact with Sm29. Furthermore, the application framework provides an integrated methodology for investigation of host-pathogen interactions and an extensive source of orthogonal data for experimental analysis. We have made the predictions available for community perusal.
MeSH term(s)	Animals ; Antigens, Helminth/metabolism ; CD59 Antigens/metabolism ; Cercaria/enzymology ; Helminth Proteins/metabolism ; Humans ; Life Cycle Stages ; Mesocricetus ; Models, Molecular ; Pancreatic Elastase/metabolism ; Protein Interaction Mapping ; Schistosoma mansoni/growth & development ; Schistosoma mansoni/metabolism ; Schistosomiasis mansoni/immunology ; Substrate Specificity ; Vaccines/immunology
Chemical Substances	Antigens, Helminth ; CD59 Antigens ; Helminth Proteins ; Vaccines ; Pancreatic Elastase (EC 3.4.21.36)
Language	English
Publishing date	2018-08-30
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-31272-1
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Article ; Online: Discovery of pyrazolopyrrolidinones as potent, broad-spectrum inhibitors of

Kavouris, John A / McCall, Laura-Isobel / Giardini, Miriam A / De Muylder, Geraldine / Thomas, Diane / Garcia-Pérez, Adolfo / Cantizani, Juan / Cotillo, Ignacio / Fiandor, Jose M / McKerrow, James H / De Oliveira, Camila I / Siqueira-Neto, Jair L / González, Silvia / Brown, Lauren E / Schaus, Scott E

Frontiers in tropical diseases

2023 Volume 3

Abstract: Introduction: Leishmaniasis is a parasitic disease that affects more than 1 million people worldwide annually, predominantly in resource-limited settings. The challenge in compound development is to exhibit potent activity against the intracellular ... ...

Abstract	Introduction: Leishmaniasis is a parasitic disease that affects more than 1 million people worldwide annually, predominantly in resource-limited settings. The challenge in compound development is to exhibit potent activity against the intracellular stage of the parasite (the stage present in the mammalian host) without harming the infected host cells. We have identified a compound series (pyrazolopyrrolidinones) active against the intracellular parasites of Methods: In this study, we performed medicinal chemistry on a newly discovered antileishmanial chemotype, with over 100 analogs tested. Studies included assessments of antileishmanial potency, toxicity towards host cells, and in vitro ADME screening of key drug properties. Results and discussion: Members of the series showed high potency against the deadliest form, visceral leishmaniasis (approximate EC Conclusion: Here, we describe preliminary structure-activity relationships for antileishmanial pyrazolopyrrolidinones, and our progress towards the identification of candidates for future in vivo assays in models of visceral and cutaneous leishmaniasis.
Language	English
Publishing date	2023-01-23
Publishing country	Switzerland
Document type	Journal Article
ISSN	2673-7515
ISSN (online)	2673-7515
DOI	10.3389/fitd.2022.1011124
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Article ; Online: Identification of Leucinostatins from

Bernatchez, Jean A / Kil, Yun-Seo / Barbosa da Silva, Elany / Thomas, Diane / McCall, Laura-Isobel / Wendt, Karen L / Souza, Julia M / Ackermann, Jasmin / McKerrow, James H / Cichewicz, Robert H / Siqueira-Neto, Jair L

ACS omega

2022 Volume 7, Issue 9, Page(s) 7675–7682

Abstract: Safe and effective treatments for Chagas disease, a potentially fatal parasitic infection associated with cardiac and gastrointestinal pathology and caused by the kinetoplastid ... ...

Abstract	Safe and effective treatments for Chagas disease, a potentially fatal parasitic infection associated with cardiac and gastrointestinal pathology and caused by the kinetoplastid parasite
Language	English
Publishing date	2022-01-28
Publishing country	United States
Document type	Journal Article
ISSN	2470-1343
ISSN (online)	2470-1343
DOI	10.1021/acsomega.1c06347
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Article ; Online: LINE-1 expression in cancer correlates with p53 mutation, copy number alteration, and S phase checkpoint.

McKerrow, Wilson / Wang, Xuya / Mendez-Dorantes, Carlos / Mita, Paolo / Cao, Song / Grivainis, Mark / Ding, Li / LaCava, John / Burns, Kathleen H / Boeke, Jef D / Fenyö, David

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 8

Abstract: Retrotransposons are genomic DNA sequences that copy themselves to new genomic locations via RNA intermediates; LINE-1 is the only active and autonomous retrotransposon in the human genome. The mobility of LINE-1 is largely repressed in somatic tissues ... ...

Abstract	Retrotransposons are genomic DNA sequences that copy themselves to new genomic locations via RNA intermediates; LINE-1 is the only active and autonomous retrotransposon in the human genome. The mobility of LINE-1 is largely repressed in somatic tissues but is derepressed in many cancers, where LINE-1 retrotransposition is correlated with p53 mutation and copy number alteration (CNA). In cell lines, inducing LINE-1 expression can cause double-strand breaks (DSBs) and replication stress. Reanalyzing multiomic data from breast, ovarian, endometrial, and colon cancers, we confirmed correlations between LINE-1 expression, p53 mutation status, and CNA. We observed a consistent correlation between LINE-1 expression and the abundance of DNA replication complex components, indicating that LINE-1 may also induce replication stress in human tumors. In endometrial cancer, high-quality phosphoproteomic data allowed us to identify the DSB-induced ATM-MRN-SMC S phase checkpoint pathway as the primary DNA damage response (DDR) pathway associated with LINE-1 expression. Induction of LINE-1 expression in an in vitro model led to increased phosphorylation of MRN complex member RAD50, suggesting that LINE-1 directly activates this pathway.
MeSH term(s)	Cell Cycle/genetics ; Cell Cycle Proteins/metabolism ; DNA Breaks, Double-Stranded ; DNA Copy Number Variations/genetics ; DNA Repair/genetics ; DNA-Binding Proteins/metabolism ; Databases, Genetic ; Gene Expression/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Long Interspersed Nucleotide Elements/genetics ; Long Interspersed Nucleotide Elements/physiology ; Neoplasms/genetics ; Nuclear Proteins/metabolism ; Proteins/genetics ; Proteins/metabolism ; Retroelements/genetics ; S Phase Cell Cycle Checkpoints/genetics ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Cell Cycle Proteins ; DNA-Binding Proteins ; L1TD1 protein, human ; Nuclear Proteins ; Proteins ; Retroelements ; Tumor Suppressor Protein p53
Language	English
Publishing date	2022-01-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2115999119
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Article ; Online: Patterns of disease on admission to children's wards and changes during a COVID-19 outbreak in KwaZulu-Natal Province, South Africa.

Jensen, C / Yannigan, Y / Mafanya, N / Majozi, N / Martin, T / Mnguni, T / Moodley, K / Morgan, M E / Moses, K / Ntombela, Z / Pansegrouw, A E / Pansegrouw, D / Ramsden, D / Van Lobenstein, J / McKerrow, N H

South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde

2022 Volume 112, Issue 4, Page(s) 279–287

Abstract: Background: Major causes of under-5 child deaths in South Africa (SA) are well recognised, and child mortality rates are falling. The focus of child health is therefore shifting from survival to disease prevention and thriving, but local data on the non- ...

Abstract	Background: Major causes of under-5 child deaths in South Africa (SA) are well recognised, and child mortality rates are falling. The focus of child health is therefore shifting from survival to disease prevention and thriving, but local data on the non-fatal disease burden are limited. Furthermore, COVID-19 has affected children's health and wellbeing, both directly and indirectly. Objectives: To describe the pattern of disease on admission of children at different levels of care, and assess whether this has been affected by COVID-19. Methods: Retrospective reviews of children's admission and discharge registers were conducted for all general hospitals in iLembe and uMgungundlovu districts in KwaZulu-Natal Province, SA, from January 2018 to September 2020. The Global Burden of Disease framework was adapted to create a data capture sheet with four broad diagnostic categories and 37 specific cause categories. Monthly admission numbers were recorded per cause category, and basic descriptive analysis was completed in Microsoft Excel. Results: Overall, 36 288 admissions were recorded across 18 hospital wards, 32.0% at district, 49.8% at regional and 18.2% at tertiary level. Communicable diseases, perinatal conditions and nutritional deficiencies (CPNs) accounted for 37.4% of admissions, non-communicable diseases (NCDs) for 43.5% and injuries for 17.1%. The distribution of broad diagnostic categories varied across levels of care, with CPNs being more common at district level and NCDs more common at regional and tertiary levels. Unintentional injuries represented the most common cause category (16.6%), ahead of lower respiratory tract infections (16.1%), neurological conditions (13.6%) and diarrhoeal disease (8.4%). The start of the local COVID-19 outbreak coincided with a 43.1% decline in the mean number of monthly admissions. Admissions due to neonatal conditions and intentional injuries remained constant during the COVID-19 outbreak, while those due to other disease groups (particularly respiratory infections) declined. Conclusions: Our study confirms previous concerns around a high burden of childhood injuries in our context. Continued efforts are needed to prevent and treat traditional neonatal and childhood illnesses. Concurrently, the management of NCDs should be prioritised, and evidence-based strategies are sorely needed to address the high injury burden in SA.
MeSH term(s)	COVID-19/epidemiology ; Child ; Disease Outbreaks ; Female ; Hospitals ; Humans ; Infant, Newborn ; Noncommunicable Diseases/epidemiology ; Pregnancy ; Retrospective Studies ; South Africa/epidemiology
Language	English
Publishing date	2022-04-04
Publishing country	South Africa
Document type	Journal Article
ZDB-ID	390968-2
ISSN	2078-5135 ; 0038-2469 ; 0256-9574
ISSN (online)	2078-5135
ISSN	0038-2469 ; 0256-9574
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