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Glutamine metabolism inhibition has dual immunomodulatory and antibacterial activities against Mycobacterium tuberculosis

Parveen et al., using immunological, and metabolomics-based assays, demonstrate the importance of host glutamine metabolism in tuberculosis pathogenesis and show host-directed activity against tuberculosis.

Sadiya Parveen
Jessica Shen
William R. Bishai
ResearchOpen Access16 Nov 2023
Nature Communications

Volume: 14, P: 1-15
Rapid in vivo detection of isoniazid-sensitive Mycobacterium tuberculosis by breath test

There is an urgent need for rapid point-of-care tools for tuberculosis diagnosis and antibiotic sensitivity analysis. Here, the authors describe a breath test that, within minutes, detects isoniazid-susceptible Mycobacterium tuberculosisin infected animals.

Seong W. Choi
Mamoudou Maiga
Graham S. Timmins
Research23 Sept 2014
Nature Communications

Volume: 5, P: 1-6
The Vasoactivity of the Fetal Lamb Ductus Arteriosus Studied in Utero

William F Friedman
Morton P Printz
Ed J Hoskins
Research01 May 1983
Pediatric Research

Volume: 17, P: 331-337
A bacterial cyclic dinucleotide activates the cytosolic surveillance pathway and mediates innate resistance to tuberculosis

William Bishai and colleagues report that cyclic-di-adenosine monophosphate produced during infection with Mycobacterium tuberculosis induces IFN-β and contributes to the innate sensing of tuberculosis.

Bappaditya Dey
Ruchi Jain Dey
William R Bishai
Research02 Mar 2015
Nature Medicine

Volume: 21, P: 401-406
Indoleamides are active against drug-resistant Mycobacterium tuberculosis

New classes of antitubercular drugs are in constant demand as drug-resistant strains of Mycobacterium tuberculosis become more prevalent. Here, the authors characterize a class of drugs that are active against various M. tuberculosisstrains, including those resistant to currently used antituberculars.

Shichun Lun
Haidan Guo
William R. Bishai
Research19 Dec 2013
Nature Communications

Volume: 4, P: 1-8
Re-engineered BCG overexpressing cyclic di-AMP augments trained immunity and exhibits improved efficacy against bladder cancer

Vaccination with BCG has been shown to induce a pre-priming effect in innate immune cells termed trained immunity. Here the authors re-engineer the BCG vaccine and show augmented immune responses, enhanced induction of trained immunity and improved antitumor efficacy in pre-clinical models of bladder cancer.

Alok Kumar Singh
Monali Praharaj
Trinity J. Bivalacqua
ResearchOpen Access15 Feb 2022
Nature Communications

Volume: 13, P: 1-16
The Mycobacterium tuberculosis protein Ldt_Mt2 is a nonclassical transpeptidase required for virulence and resistance to amoxicillin

A new transpeptidase that modifies the structure of the cell wall of Mycobacterium tuberculosis is important for bacterial virulence and could become the target of new antituberculosis agents.

Radhika Gupta
Marie Lavollay
Gyanu Lamichhane
Research21 Mar 2010
Nature Medicine

Volume: 16, P: 466-469
Inhibition of host PARP1 contributes to the anti-inflammatory and antitubercular activity of pyrazinamide

The mode of action of the tuberculosis antibiotic pyrazinamide is poorly understood. Here, Krug et al show that pyrazinamide inhibits the immune regulator PARP1 and demonstrate PARP1 inhibition as a host-directed therapy.

Stefanie Krug
Manish Gupta
William R. Bishai
ResearchOpen Access09 Dec 2023
Nature Communications

Volume: 14, P: 1-15
Isoniazid resistance without a loss of fitness in Mycobacterium tuberculosis

The treatment ofMycobacterium tuberculosis with drugs such as isoniazid often results in drug resistance, but the mechanisms leading to the resistance are not fully known. In this study, an M. tuberculosisstrain lacking the sigma factor I is shown to be resistant to isoniazid.

Jong-Hee Lee
Nicole C. Ammerman
William R. Bishai
Research20 Mar 2012
Nature Communications

Volume: 3, P: 1-8
Inhibition of innate immune cytosolic surveillance by an M. tuberculosis phosphodiesterase

A mycobacterial phosphodiesterase, CdnP, hydrolyzes bacteria-derived 3′,5′-c-di-AMP as well as host-generated 2′,3′-cGAMP, which activates the host cytosolic surveillance pathway, to dampen host responses.

Ruchi Jain Dey
Bappaditya Dey
William R Bishai
Research12 Dec 2016
Nature Chemical Biology

Volume: 13, P: 210-217
Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance

Ashlee Earl and colleagues analyze whole-genome sequences from 5,310 Mycobacterium tuberculosis isolates from five continents. They find that resistance to isoniazid arises before rifampicin resistance across all of the lineages, geographical regions and time periods.

Abigail L Manson
Keira A Cohen
Ashlee M Earl
Research16 Jan 2017
Nature Genetics

Volume: 49, P: 395-402
Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases

The Inflammatory Bowel Disease Multi’omics Database includes longitudinal data encompassing a multitude of analyses of stool, blood and biopsies of more than 100 individuals, and provides a comprehensive description of host and microbial activities in inflammatory bowel diseases.

Jason Lloyd-Price
Cesar Arze
Curtis Huttenhower
ResearchOpen Access29 May 2019
Nature

Volume: 569, P: 655-662
Latent Mycobacterium tuberculosis–persistence, patience, and winning by waiting

Yukari C. Manabe
William R. Bishai
Reviews01 Dec 2000
Nature Medicine

Volume: 6, P: 1327-1329
Locking down metabolism

An allosteric inhibitor of Mycobacterium tuberculosis tryptophan synthase—an enzyme that is nonessential for in vitro growth—has potent antimicrobial activity, revealing a potentially expanded target list for antimicrobials and greater chemical space for new inhibitors.

William R Bishai
News & Views18 Aug 2017
Nature Chemical Biology

Volume: 13, P: 925-926
Cyclic AMP intoxication of macrophages by a Mycobacterium tuberculosis adenylate cyclase

Mycobacterium tuberculosis induces a cyclic AMP (cAMP) burst within infected macrophages that influences cell signalling, but the underlying mechanism for this increase in cAMP remains unclear. It is now shown that it is produced by a bacterial adenylate cyclase that facilitates delivery of bacterial-derived cAMP into the macrophage cytoplasm, presumably enhancing virulence through the activation of downstream signalling pathways.

Nisheeth Agarwal
Gyanu Lamichhane
William R. Bishai
Research10 Jun 2009
Nature

Volume: 460, P: 98-102
TRAV1-2⁺ CD8⁺ T-cells including oligoconal expansions of MAIT cells are enriched in the airways in human tuberculosis

Emily Wong et al. observe that Mycobacterium tuberculosis (Mtb) infection induces recruitment and expansion of a CD8⁺ TRAV1-2⁺ T-cell population in the airways of human patients. T cell receptor analysis showed expansion of this cell population, including oligoclonal MAIT cells, in sites where Mtb antigens are present, suggesting they act as sentinels of pulmonary infection.

Emily B. Wong
Marielle C. Gold
David M. Lewinsohn
ResearchOpen Access05 Jun 2019
Communications Biology

Volume: 2, P: 1-13

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Glutamine metabolism inhibition has dual immunomodulatory and antibacterial activities against Mycobacterium tuberculosis

Rapid in vivo detection of isoniazid-sensitive Mycobacterium tuberculosis by breath test

The Vasoactivity of the Fetal Lamb Ductus Arteriosus Studied in Utero

A bacterial cyclic dinucleotide activates the cytosolic surveillance pathway and mediates innate resistance to tuberculosis

Indoleamides are active against drug-resistant Mycobacterium tuberculosis

Re-engineered BCG overexpressing cyclic di-AMP augments trained immunity and exhibits improved efficacy against bladder cancer

The Mycobacterium tuberculosis protein Ldt_Mt2 is a nonclassical transpeptidase required for virulence and resistance to amoxicillin

Inhibition of host PARP1 contributes to the anti-inflammatory and antitubercular activity of pyrazinamide

Isoniazid resistance without a loss of fitness in Mycobacterium tuberculosis

Inhibition of innate immune cytosolic surveillance by an M. tuberculosis phosphodiesterase

Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance

Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases

Latent Mycobacterium tuberculosis–persistence, patience, and winning by waiting

Locking down metabolism

Cyclic AMP intoxication of macrophages by a Mycobacterium tuberculosis adenylate cyclase

TRAV1-2⁺ CD8⁺ T-cells including oligoconal expansions of MAIT cells are enriched in the airways in human tuberculosis

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