Identification of Anti-Mycobacterium and Anti-Legionella Compounds With Potential Distinctive Structural Scaffolds From an HD-PBL Using Phenotypic Screens in Amoebae Host Models

Frontiers in Microbiology
Nabil HannaThierry Soldati

Abstract

Tubercular Mycobacteria and Legionella pneumophila are the causative agents of potentially fatal respiratory diseases due to their intrinsic pathogenesis but also due to the emergence of antibiotic resistance that limits treatment options. The aim of our study was to explore the antimicrobial activity of a small ligand-based chemical library of 1255 structurally diverse compounds. These compounds were screened in a combination of three assays, two monitoring the intracellular growth of the pathogenic bacteria, Mycobacterium marinum and L. pneumophila, and one assessing virulence of M. marinum. We set up these assays using two amoeba strains, the genetically tractable social amoeba Dictyostelium discoideum and the free-living amoeba Acanthamoeba castellanii. In summary, 64 (5.1%) compounds showed anti-infective/anti-virulence activity in at least one of the three assays. The intracellular assays hit rate varied between 1.7% (n = 22) for M. marinum and 2.8% (n = 35) for L. pneumophila with seven compounds in common for both pathogens. In parallel, 1.2% (n = 15) of the tested compounds were able to restore D. discoideum growth in the presence of M. marinum spiked in a lawn of food bacteria. We also validated the generality of the ...Continue Reading

References

May 2, 1998·Science·R SakowiczL S Goldstein
Mar 29, 2000·Journal of Molecular Biology·R IyerA H Delcour
Apr 28, 2004·Emerging Infectious Diseases·Gilbert GreubDidier Raoult
Dec 17, 2004·Nature·Christopher Lipinski, Andrew Hopkins
Jan 11, 2005·Applied and Environmental Microbiology·Maëlle MolmeretYousef Abu Kwaik
Feb 1, 2005·Cellular Microbiology·Michael Steinert, Klaus Heuner
Apr 6, 2005·Journal of Chemical Information and Modeling·David VidalMiquel Pons
Jul 9, 2005·Science·Stephen B LongRoderick Mackinnon
Feb 15, 2007·Environmental Microbiology·Hubert HilbiSimon Urwyler
Apr 19, 2007·Journal of Natural Products·Josefin LarssonAnders Backlund
May 9, 2007·Nature Chemical Biology·Sovan SarkarDavid C Rubinsztein
Jul 20, 2007·Nature Chemical Biology·Anang A Shelat, R Kiplin Guy
Oct 3, 2007·The Journal of Pharmacology and Experimental Therapeutics·Rosanna SupinoFranco Zunino
Jun 10, 2008·The Journal of Biological Chemistry·Liling YangJianren Mao
Jun 14, 2008·Current Opinion in Microbiology·Pierre Cosson, Thierry Soldati
Dec 17, 2008·Journal of Computer-aided Molecular Design·Josefin RosénAnders Backlund
Jan 2, 2009·Journal of Medicinal Chemistry·Yoshinori SugimotoTohru Oishi
Jan 10, 2009·Nature Protocols·Romain FroquetPierre Cosson
May 13, 2009·Journal of Chemical Information and Modeling·Johannes KirchmairGerhard Wolber
Oct 29, 2009·Cell Communication and Signaling : CCS·Matthias Sieber, Ria Baumgrass
Nov 26, 2009·Journal of Medicinal Chemistry·Enea SalsiAndrea Mozzarelli
Dec 8, 2009·Journal of Molecular Biology·T BertrandM Mathieu
Oct 21, 2010·Molecular Systems Biology·Jonathan BoulaisMichel Desjardins
Oct 30, 2010·Journal of Enzyme Inhibition and Medicinal Chemistry·Yasser BustanjiHatim S Alkhatib
Feb 11, 2011·Protein Science : a Publication of the Protein Society·Céline Schalk-HihiLawrence C Kuo
Feb 12, 2011·Journal of Medicinal Chemistry·Steven L SwannPhilip J Hajduk
Mar 2, 2011·Nature Reviews. Drug Discovery·Ricardo MacarronG Sitta Sittampalam
Mar 8, 2011·Bioorganic & Medicinal Chemistry Letters·Qianyi ChenAmarnath Natarajan
Jun 10, 2011·Expert Opinion on Therapeutic Patents·Xiaoyun LuQidong You

❮ Previous
Next ❯

Citations

Mar 26, 2021·Frontiers in Cell and Developmental Biology·Romain BodinierPierre Cosson
Apr 5, 2021·Cellular Microbiology·Neeraja Subhash, Varadharajan Sundaramurthy

❮ Previous
Next ❯

Methods Mentioned

BETA
Assay

Software Mentioned

ChemGPS
Lingo
ChemBioDraw
Netwalker1
GraphPad Prism
OpenEye
Rtsne
R
Excel
NP

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.