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Mycobacterium

  • Lack of Specificity of Phenotypic Screens for Inhibitors of the <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span> FAS-II System
    Mechanisms of Action: Physiological Effects
    Lack of Specificity of Phenotypic Screens for Inhibitors of the Mycobacterium tuberculosis FAS-II System

    Phenotypic screening of inhibitors of the essential Mycobacterium tuberculosis FAS-II dehydratase HadAB led to the identification of GSK3011724A, a compound previously reported to inhibit the condensation step of FAS-II. Whole-cell-based and cell-free assays confirmed the lack of activity of GSK3011724A against the dehydratase despite evidence of cross-resistance...

    Anna E. Grzegorzewicz, Joël Lelièvre, Jorge Esquivias, Bhanupriya Angala, Jiuyu Liu, Richard E. Lee, Michael R. McNeil, Mary Jackson
  • The Unique C-Terminal Extension of Mycobacterial F-ATP Synthase Subunit α Is the Major Contributor to Its Latent ATP Hydrolysis Activity
    Mechanisms of Action: Physiological Effects
    The Unique C-Terminal Extension of Mycobacterial F-ATP Synthase Subunit α Is the Major Contributor to Its Latent ATP Hydrolysis Activity

    Mycobacterial F1Fo-ATP synthases (α3:β3:γ:δ:ε:a:b:b′:c9) are incapable of ATP-driven proton translocation due to their latent ATPase activity. This prevents wasting of ATP and altering of the proton motive force, whose dissipation is lethal to mycobacteria. We demonstrate that the mycobacterial C-terminal extension of nucleotide-binding subunit α...

    Chui-Fann Wong, Gerhard Grüber
  • Adduct Formation of Delamanid with NAD in Mycobacteria
    Mechanisms of Action: Physiological Effects
    Adduct Formation of Delamanid with NAD in Mycobacteria

    Delamanid (DLM), a nitro-dihydroimidazooxazole derivative currently approved for pulmonary multidrug-resistant tuberculosis (TB) therapy, is a prodrug activated by mycobacterial 7,8-didemethyl-8-hydroxy 5-deazaflavin electron transfer coenzyme (F420)-dependent nitroreductase (Ddn). Despite inhibiting the biosynthesis of a subclass of mycolic acids, the active DLM metabolite remained unknown. Comparative liquid chromatography-...

    Mikayo Hayashi, Akihito Nishiyama, Ryuki Kitamoto, Yoshitaka Tateishi, Mayuko Osada-Oka, Yukiko Nishiuchi, Shaban A. Kaboso, Xiuhao Chen, Mamoru Fujiwara, Yusuke Inoue, Yoshikazu Kawano, Masanori Kawasaki, Tohru Abe, Tsutomu Sato, Kentaro Kaneko, Kimiko Itoh, Sohkichi Matsumoto, Makoto Matsumoto
  • Free
    Successful Systemic and Topical Treatment of <span class="named-content genus-species" id="named-content-1">Mycobacterium abscessus</span> Otomastoiditis
    Editor's Pick Challenging Clinical Case in Antimicrobial Resistance
    Successful Systemic and Topical Treatment of Mycobacterium abscessus Otomastoiditis

    Mycobacterium abscessus is an extensively drug-resistant opportunistic pathogen that can cause chronic otomastoiditis. There are no evidence-based treatment regimens for this severe infection. We treated four children with M. abscessus otomastoiditis with a structured regimen of topical imipenem and...

    Floor van Wijk, Jérôme Waterval, Koen van Aerde, Stefanie S. V. Henriet, F. J. Anton Meijer, Lennaert C. Borra, Rob E. Aarnoutse, Jakko van Ingen
  • Open Access
    Watching DNA Replication Inhibitors in Action: Exploiting Time-Lapse Microfluidic Microscopy as a Tool for Target-Drug Interaction Studies in <em>Mycobacterium</em>
    Mechanisms of Action: Physiological Effects
    Watching DNA Replication Inhibitors in Action: Exploiting Time-Lapse Microfluidic Microscopy as a Tool for Target-Drug Interaction Studies in Mycobacterium

    Spreading resistance to antibiotics and the emergence of multidrug-resistant strains have become frequent in many bacterial species, including mycobacteria, which are the causative agents of severe diseases and which have profound impacts on global health.

    Damian Trojanowski, Marta Kołodziej, Joanna Hołówka, Rolf Müller, Jolanta Zakrzewska-Czerwińska
  • <span class="named-content genus-species" id="named-content-1">Mycobacterium abscessus</span> Cells Have Altered Antibiotic Tolerance and Surface Glycolipids in Artificial Cystic Fibrosis Sputum Medium
    Biologic Response Modifiers
    Mycobacterium abscessus Cells Have Altered Antibiotic Tolerance and Surface Glycolipids in Artificial Cystic Fibrosis Sputum Medium

    Mycobacterium abscessus is a biofilm-forming, multidrug-resistant nontuberculous mycobacterial (NTM) pathogen increasingly found in cystic fibrosis patients. Antibiotic treatment for these infections is often unsuccessful, partly due to M. abscessus’s high intrinsic antibiotic resistance.

    ...
    Augusto Cesar Hunt-Serracin, Brian J. Parks, Joseph Boll, Cara C. Boutte
  • Indole-2-Carboxamides Are Active against <em>Mycobacterium abscessus</em> in a Mouse Model of Acute Infection
    Chemistry; Biosynthesis
    Indole-2-Carboxamides Are Active against Mycobacterium abscessus in a Mouse Model of Acute Infection

    Nontuberculous mycobacteria (NTM) pathogens particularly infect patients with structural lung disorders. We previously reported novel indole-2-carboxamides (ICs) that are active against a wide panel of NTM pathogens.

    Amit N. Pandya, Pavan K. Prathipati, Pooja Hegde, Wei Li, Kyle F. Graham, Subhra Mandal, Kristen M. Drescher, Christopher J. Destache, Diane Ordway, Mary Jackson, E. Jeffrey North
  • Open Access
    Clinical Therapeutics
    Rifabutin Acts in Synergy and Is Bactericidal with Frontline Mycobacterium abscessus Antibiotics Clarithromycin and Tigecycline, Suggesting a Potent Treatment Combination
    Mark Pryjma, Ján Burian, Charles J. Thompson
  • Open Access
    Mechanisms of Resistance
    Imidazopyridine Compounds Inhibit Mycobacterial Growth by Depleting ATP Levels
    Theresa O'Malley, Torey Alling, Julie V. Early, Heather A. Wescott, Anuradha Kumar, Garrett C. Moraski, Marvin J. Miller, Thierry Masquelin, Philip A. Hipskind, Tanya Parish
  • Experimental Therapeutics
    Evidence for Inhibition of Topoisomerase 1A by Gold(III) Macrocycles and Chelates Targeting Mycobacterium tuberculosis and Mycobacterium abscessus
    Rashmi Gupta, Carolina Rodrigues Felix, Matthew P. Akerman, Kate J. Akerman, Cathryn A. Slabber, Wenjie Wang, Jessie Adams, Lindsey N. Shaw, Yuk-Ching Tse-Dinh, Orde Q. Munro, Kyle H. Rohde

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