Article
Microbiology
Alan A. Schmalstig, Andrew Wiggins, Debbie Badillo, Katherine S. Wetzel, Graham F. Hatfull, Miriam Braunstein
Summary: Researchers have found that bacteriophages can enter mammalian cells and infect and kill intracellular M. abscessus. This discovery highlights the potential of phage therapy for treating intracellular bacterial infections, specifically M. abscessus.
Review
Immunology
Michal Bar-Oz, Michal Meir, Daniel Barkan
Summary: Non-tuberculous mycobacteria (NTM) are a group of diverse organisms that are increasingly recognized as pathogens. Among NTMs, Mycobacterium abscessus (Mabs) causes severe and difficult to treat infections. The knowledge of the mechanisms of virulence in Mabs is limited compared to that in M. tuberculosis (Mtb). This review provides a framework and knowledge base for researchers interested in studying the secretion of virulence-associated molecules in Mabs.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Stephen Adonai Leon-Icaza, Salimata Bagayoko, Romain Verge, Nino Iakobachvili, Chloe Ferrand, Talip Aydogan, Celia Bernard, Angelique Sanchez Dafun, Marlene Murris-Espin, Julien Mazieres, Pierre Jean Bordignon, Serge Mazeres, Pascale Bernes-Lasserre, Victoria Rame, Jean-Michel Lagarde, Julien Marcoux, Marie-Pierre Bousquet, Christian Chalut, Christophe Guilhot, Hans Clevers, Peter J. Peters, Virginie Molle, Geanncarlo Lugo-Villarino, Kaymeuang Cam, Laurence Berry, Etienne Meunier, Celine Cougoule
Summary: Although Mabs infection can induce oxidative stress, pharmacological activation of antioxidant pathways can better control Mabs growth and reduce its virulence. Genetic and pharmacological inhibition of CFTR is associated with improved Mabs growth and increased virulence. Pharmacological activation of antioxidant pathways can inhibit Mabs growth and improve efficacy when combined with cefoxitin.
Article
Cell Biology
Juan Manuel Belardinelli, Deepshikha Verma, Wei Li, Charlotte Avanzi, Crystal J. Wiersma, John T. Williams, Benjamin K. Johnson, Matthew Zimmerman, Nicholas Whittel, Bhanupriya Angala, Han Wang, Victoria Jones, Veronique Dartois, Vinicius C. N. de Moura, Mercedes Gonzalez-Juarrero, Camron Pearce, Alan R. Schenkel, Kenneth C. Malcolm, Jerry A. Nick, Susan A. Charman, Timothy N. C. Wells, Brendan K. Podell, Jonathan L. Vennerstrom, Diane J. Ordway, Robert B. Abramovitch, Mary Jackson
Summary: This study found that antimalarial drugs can serve as potent inhibitors of M. abscessus, offering potential for clinical treatment.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Jerry A. Nick, Rebekah M. Dedrick, Alice L. Gray, Eszter K. Vladar, Bailey E. Smith, Krista G. Freeman, Kenneth C. Malcolm, L. Elaine Epperson, Nabeeh A. Hasan, Jo Hendrix, Kimberly Callahan, Kendra Walton, Brian Vestal, Emily Wheeler, Noel M. Rysavy, Katie Poch, Silvia Caceres, Valerie K. Lovell, Katherine B. Hisert, Vinicius Calado de Moura, Delphi Chatterjee, Prithwiraj De, Natalia Weakly, Stacey L. Martiniano, David A. Lynch, Charles L. Daley, Michael Strong, Fan Jia, Graham F. Hatfull, Rebecca M. Davidson
Summary: This study describes a successful phage treatment of treatment-refractory Mycobacterium abscessus pulmonary infection in a patient with severe lung disease. The phages used in the treatment were engineered to enhance their ability to lyse M. abscessus and were specifically selected based on their effectiveness against the patient's bacterial isolate. The treatment resulted in genetic stability of the bacterial isolate and improved clinical symptoms in the patient.
Article
Multidisciplinary Sciences
Josephine M. Bryant, Karen P. Brown, Sophie Burbaud, Isobel Everall, Juan M. Belardinelli, Daniela Rodriguez-Rincon, Dorothy M. Grogono, Chelsea M. Peterson, Deepshikha Verma, Ieuan E. Evans, Christopher Ruis, Aaron Weimann, Divya Arora, Sony Malhotra, Bridget Bannerman, Charlotte Passemar, Kerra Templeton, Gordon MacGregor, Kasim Jiwa, Andrew J. Fisher, Tom L. Blundell, Diane J. Ordway, Mary Jackson, Julian Parkhill, R. Andres Floto
Summary: The study suggests that epigenetic modifiers acquired through horizontal gene transfer can lead to sudden increases in the pathogenic potential of specific environmental clones, while allopatric parallel evolution during chronic lung infection promotes rapid increases in virulence. The findings indicate that constrained pathogenic evolution is observed while person-to-person transmission remains indirect.
Article
Microbiology
Uday S. Ganapathy, Martin Gengenbacher, Thomas Dick
Summary: Benzoxaboroles, including the clinical candidate epetraborole, have shown activity against Mycobacterium abscessus, expanding the options for developing benzoxaborole-based candidates to treat M. abscessus lung disease.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Wassihun Wedajo Aragaw, Christine Roubert, Evelyne Fontaine, Sophie Lagrange, Matthew D. Zimmerman, Veronique Dartois, Martin Gengenbacher, Thomas Dick
Summary: Cyclohexyl-griselimycin, a preclinical candidate for treating tuberculosis, has shown activity against the drug-resistant Mycobacterium abscessus in vitro and in a mouse model. This discovery provides a new lead compound for M. abscessus drug development and supports the strategy of screening chemical matter from TB drug discovery to expedite the discovery of novel antibiotics against M. abscessus.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Multidisciplinary Sciences
Adam M. Crowe, Jessica M. C. Krekhno, Kirstin L. Brown, Jayesh A. Kulkarni, Katherine C. Yam, Lindsay D. Eltis
Summary: Mycobacterium abscessus contains genes predicted to encode two steroid catabolic pathways, and unlike other similar bacteria, it lacks genes encoding MCP hydrolase. The study shows that cholesterol is essential for the growth of the bacteria and the catabolic pathways are not solely dependent on coenzyme A sequestration.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Microbiology
Abdeldjalil Madani, Dereje A. Negatu, Abdellatif El Marrouni, Randy R. Miller, Christopher W. Boyce, Nicholas Murgolo, Christopher J. Bungard, Matthew D. Zimmerman, Veronique Dartois, Martin Gengenbacher, David B. Olsen, Thomas Dick
Summary: Tricyclic pyrrolopyrimidines (TPPs) are a new class of antibacterials that inhibit the ATPase activity of DNA gyrase to combat Mycobacterium abscessus.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Dereje Abate Negatu, Andreas Beuchel, Abdeldjalil Madani, Nadine Alvarez, Chao Chen, Wassihun Wedajo Aragaw, Matthew D. Zimmerman, Benoit Laleu, Martin Gengenbacher, Veronique Dartois, Peter Imming, Thomas Dick
Summary: The study identified P4Cs as a novel class of antibacterial drugs against the M. abscessus complex, exhibiting bactericidal and antibiofilm activities, and potential for treating drug-resistant M. abscessus disease.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Jickky Palmae Sarathy, Matthew D. Zimmerman, Martin Gengenbacher, Veronique Dartois, Thomas Dick
Summary: The antituberculosis candidate OPC-167832 was found to be active against Mycobacterium abscessus, but its moderate potency and lack of efficacy in a mouse model makes it unsuitable for repurposing. The study identifies OPC-167832-DprE1 as a lead-target couple for optimizing treatment of M. abscessus.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Chemistry, Multidisciplinary
Min Jia Khor, Agnieszka Broda, Markus Kostrzewa, Francis Drobniewski, Gerald Larrouy-Maumus
Summary: Rapid diagnosis of bacterial infections is crucial for successful treatment. Traditional methods relying on protein detection may not be able to distinguish subspecies. This study proposes a new method using ethanol with a specific matrix for accurate subspecies identification.
FRONTIERS IN CHEMISTRY
(2021)
Article
Microbiology
Noemi Poerio, Camilla Riva, Tommaso Olimpieri, Marco Rossi, Nicola Lore, Federica De Santis, Lucia Henrici De Angelis, Fabiana Ciciriello, Marco M. D'Andrea, Vincenzina Lucidi, Daniela M. Cirillo, Maurizio Fraziano
Summary: Mycobacterium abscessus is a highly-resistant pathogen that causes severe pulmonary infections, particularly in vulnerable patients. The development of new therapeutic strategies is urgently needed due to the limited treatment options. This study demonstrates that apoptotic body-like liposomes loaded with phosphatidylinositol 5-phosphate can enhance the antimycobacterial response and reduce inflammation. Combination therapy with antibiotics and bioactive liposomes further reduces mycobacterial burden and inflammatory response. These findings provide a conceptual basis for a novel therapeutic approach to control M. abscessus infection and related immunopathogenic responses.
MICROBIOLOGY SPECTRUM
(2022)
Review
Microbiology
Saubashya Sur, Tanushree Patra, Mistu Karmakar, Anindita Banerjee
Summary: This article reviews the importance of bioinformatic studies on Mycobacterium abscessus and highlights the use of computational methods to understand factors responsible for pathogen survival and resistance. The utility of genome-based studies in comprehending disease progression, tracing transmission routes, and global epidemiological outbreaks is emphasized. The article also underscores the significance of interdisciplinary research in combating M. abscessus.
CRITICAL REVIEWS IN MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jeremie Rosain, Anna-Lena Neehus, Jeremy Manry, Rui Yang, Jeremie Le Pen, Wassim Daher, Zhiyong Liu, Yi-Hao Chan, Natalia Tahuil, Ozden Turel, Mathieu Bourgey, Masato Ogishi, Jean-Marc Doisne, Helena M. Izquierdo, Takayoshi Shirasaki, Tom Le Voyer, Antoine Guerin, Paul Bastard, Marcela Moncada-Velez, Ji Eun Han, Taushif Khan, Franck Rapaport, Seon-Hui Hong, Andrew Cheung, Kathrin Haake, Barbara C. Mindt, Laura Perez, Quentin Philippot, Danyel Lee, Peng Zhang, Darawan Rinchai, Fatima Al Ali, Manar Mahmoud Ahmad Ata, Mahbuba Rahman, Jessica N. Peel, Soren Heissel, Henrik Molina, Yasemin Kendir-Demirkol, Rasheed Bailey, Shuxiang Zhao, Jonathan Bohlen, Mathieu Mancini, Yoann Seeleuthner, Marie Roelens, Lazaro Lorenzo, Camille Soudee, Maria Elvira Josefina Paz, Maria Laura Gonzalez, Mohamed Jeljeli, Jean Soulier, Serge Romana, Anne-Sophie L'Honneur, Marie Materna, Ruben Martinez-Barricarte, Mathieu Pochon, Carmen Oleaga-Quintas, Alexandre Michev, Melanie Migaud, Romain Levy, Marie-Alexandra Alyanakian, Flore Rozenberg, Carys A. Croft, Guillaume Vogt, Jean-Francois Emile, Laurent Kremer, Cindy S. Ma, Jorg H. Fritz, Stanley M. Lemon, Andras N. Spaan, Nicolas Manel, Laurent Abel, Margaret R. MacDonald, Stephanie Boisson-Dupuis, Nico Marr, Stuart G. Tangye, James P. Di Santo, Qian Zhang, Shen-Ying Zhang, Charles M. Rice, Vivien Beziat, Nico Lachmann, David Langlais, Jean-Laurent Casanova, Philippe Gros, Jacinta Bustamante
Summary: Inborn errors of IFN-g-dependent macrophagic immunity cause mycobacterial diseases, while inborn errors of IFN-a/b-dependent intrinsic immunity lead to viral diseases. Children with complete IRF1 deficiency have early-onset, life-threatening diseases caused by weakly virulent mycobacteria and related intramacrophagic pathogens. Their IFN-a/b-dependent antiviral immunity is largely normal, but their IFN-g-dependent macrophagic immunity is impaired.
Article
Chemistry, Medicinal
Marianna Stampolaki, Satish R. Malwal, Nadine Alvarez-Cabrera, Zijun Gao, Mohammad Moniruzzaman, Svitlana O. Babii, Nikolaos Naziris, Andre Rey-Cibati, Mariana Valladares-Delgado, Andreea L. Turcu, Kyung-Hwa Baek, Phan Trong-Nhat, Hyeryon Lee, Mattheo Alcaraz, Savannah Watson, Mariette van der Watt, Dina Coertzen, Natasa Efstathiou, Maria Chountoulesi, Carolyn M. Shoen, Ioannis P. Papanastasiou, Jose Brea, Michael H. Cynamon, Lyn-Marie Birkholtz, Laurent Kremer, Joo Hwan No, Santiago Vazquez, Gustavo Benaim, Costas Demetzos, Helen I. Zgurskaya, Thomas Dick, Eric Oldfield, Antonios D. Kolocouris
Summary: SQ109 is a potent tuberculosis drug candidate that inhibits MmpL3 transporter and cell wall biosynthesis in Mycobacterium tuberculosis. It also shows activity against bacteria and protozoan parasites. In this study, 18 analogs of SQ109 were synthesized and tested against various microorganisms. Some analogs showed more activity than SQ109 against drug-resistant M. abscessus and P. falciparum. These analogs also exhibited low toxicity to human cells, making them potential antimalarial drug leads. Surface plasmon resonance and differential scanning calorimetry were used to study the binding of inhibitors to MmpL3 and lipid membranes, respectively.
ACS INFECTIOUS DISEASES
(2023)
Article
Multidisciplinary Sciences
Jona Karam, Fabien P. Blanchet, Eric Vives, Prisca Boisguerin, Yves-Marie Boudehen, Laurent Kremer, Wassim Daher
Summary: It has been discovered that neutralizing anti-CD81 antibodies and deletion of the large extracellular loop (LEL) of CD81 significantly reduce the uptake of Mab by macrophages. Saturation of Mab with soluble GST-CD81-LEL or CD81-LEL-derived peptides also decreases the internalization of the bacteria. The study unveils AhpC as a major interactant of CD81-LEL, and pre-exposure of macrophages with soluble AhpC inhibits mycobacterial uptake while overexpression of AhpC in Mab enhances its internalization. These findings highlight the previously unexplored role of CD81/AhpC in promoting the uptake of pathogenic mycobacteria by host cells.
Article
Microbiology
Francoise Roquet-Baneres, Mattheo Alcaraz, Claire Hamela, Jan Abendroth, Thomas E. Edwards, Laurent Kremer
Summary: Researchers have discovered that a compound called NITD-916 displays potent antimicrobial activity against M. fortuitum both in vitro and in vivo. This compound inhibits the growth of M. fortuitum by targeting InhA(MFO) and shows promising effectiveness against drug resistance. This study suggests that NITD-916 could be a potential drug for the treatment of M. fortuitum pulmonary diseases.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Review
Infectious Diseases
Mattheo Alcaraz, Thomas E. Edwards, Laurent Kremer
Summary: The treatment options for Mycobacterium abscessus infections are limited. The authors review the potential drug targets in M. abscessus related to the mycolic acid biosynthetic pathway and discuss the activity of inhibitors targeting MmpL3 and InhA. They highlight the potential of NITD-916 as a direct InhA inhibitor for the treatment of multidrug resistant M. abscessus infections.
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
(2023)
Editorial Material
Microbiology
Wassim Daher, Laurent Kremer
Summary: Mycobacterium abscessus relies on high levels of biotin biosynthesis during infection to adapt to the alkaline lung airway environment by remodelling cell envelope through fatty acid changes that increase fluidity.
NATURE MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Albertus Viljoen, Alain Vercellone, Myriam Chimen, Gerald Gaibelet, Serge Mazeres, Jerome Nigou, Yves F. Dufrene
Summary: The pathogenic bacterium Mycobacterium tuberculosis evades the immune system by binding to the C-type lectin DC-SIGN on dendritic cells. Our multidisciplinary study combining atomic force microscopy, Forster resonance energy transfer, and bioassays unravels the molecular mechanism behind the selective recognition of this receptor. We found that the distribution of DC-SIGN ligands differs between MyMTBC species, with dense nanodomains observed on M. bovis BCG. Upon bacteria-host cell adhesion, ligand nanodomains induce the recruitment and clustering of DC-SIGN, highlighting the importance of ligand clustering in pathogen recognition.
Article
Microbiology
Scott A. Cunningham, Christophe Rodriguez, Paul-Louis Woerther, Christophe Menigaux, Thomas Bauer, Jean-Louis Herrmann, Martin Rottman, Anne-Laure Roux, Jean-Louis Gaillard, Robin Patel, Faten El Sayed
Summary: In this study, we report the first emergence of dual resistance to levofloxacin and rifampin in C. avidum in vivo, in a patient who received both antibiotics orally during salvage debridement and implant retention of an ODRI. This study highlights potential limitations of the combination of oral rifampin and levofloxacin in patients undergoing these surgical procedures and the potential need to evaluate specific optimal therapy for emerging ODRI pathogens.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
John Jairo Aguilera-Correa, Yves-Marie Boudehen, Laurent Kremer
Summary: By analyzing two-dimensional images of fluorescent or Congo red-stained M. abscessus colony-biofilms grown on a membrane, we found that colony-biofilms of smooth and rough variants of M. abscessus responded differently to rifabutin and bedaquiline, highlighting the importance of morphotype in addressing antibiotic treatment for biofilm-related infections in patients.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Tonia Dargham, Ivy Mallick, Laurent Kremer, Pierre Santucci, Stephane Canaan
Summary: This article presents a computational analysis of the core proteome associated with intrabacterial lipid inclusions (ILI) in Mycobacterium tuberculosis (Mtb). The study provides insights into ILI metabolism and tuberculosis pathogenesis, making it a valuable resource for the mycobacterial community.
Article
Microbiology
Yves-Marie Boudehen, Yara Tasrini, John Jairo Aguilera-Correa, Mattheo Alcaraz, Laurent Kremer
Summary: Mycobacterium abscessus is a multi-drug-resistant non-tuberculous mycobacterial species causing tuberculosis-like lung infections. This study developed a method to silence the expression of specific genes in M. abscessus during host infection, demonstrating the essentiality of mmpL3 for bacterial growth.
MICROBIOLOGY SPECTRUM
(2023)
Article
Chemistry, Medicinal
Marianna Stampolaki, Satish R. Malwal, Nadine Alvarez-Cabrera, Zijun Gao, Mohammad Moniruzzaman, Svitlana O. Babii, Nikolaos Naziris, Andre Rey-Cibati, Mariana Valladares-Delgado, Andreea L. Turcu, Kyung-Hwa Baek, Trong-Nhat Phan, Hyeryon Lee, Mattheo Alcaraz, Savannah Watson, Mariette van der Watt, Dina Coertzen, Natasa Efstathiou, Maria Chountoulesi, Carolyn M. Shoen, Ioannis P. Papanastasiou, Jose Brea, Michael H. Cynamon, Lyn-Marie Birkholtz, Laurent Kremer, Joo Hwan No, Santiago Vazquez, Gustavo Benaim, Costas Demetzos, Helen I. Zgurskaya, Thomas Dick, Eric Oldfield, Antonios D. Kolocouris
Summary: SQ109 is a potent tuberculosis drug candidate that targets cell wall biosynthesis by inhibiting MmpL3 transporter. It also shows activity against bacteria and protozoan parasites. By synthesizing analogs of SQ109, higher activity against drug-resistant strains of Mycobacterium abscessus and Plasmodium falciparum was found, making them potential new drug leads. Binding studies suggest that MmpL3 is not a major target in mycobacteria. Rating: 7/10.
ACS INFECTIOUS DISEASES
(2023)
Review
Microbiology
Wassim Daher, Virginia Pichler, Jona Karam, Olivier Neyrolles, Laurent Kremer
Summary: This review summarizes the complexity of interactions between mycobacterial ligands and host receptors during infection and pathogenesis. It highlights the recognition of pathogen-associated molecular patterns by phagocytic pattern recognition receptors as the first step of the infection process. It discusses the downstream effects of receptor-mediated pathways in promoting mycobacterial survival or activating host immune defenses, and the potential of mycobacterial surface molecules as therapeutic targets, diagnostic markers, or vaccine candidates.
FEMS MICROBIOLOGY REVIEWS
(2023)
Article
Multidisciplinary Sciences
Shekhar, Mattheo Alcaraz, Pule Seboletswe, Neha Manhas, Laurent Kremer, Parvesh Singh, Vipan Kumar
Summary: Triclosan azo-adducts have shown significant activity against Mycobacterium tuberculosis and non-tuberculous mycobacteria. The most potent compound in the series exhibited higher activity against drug-resistant strains and lower cytotoxicity to human cells. These compounds may work through a distinct mechanism.
Article
Nanoscience & Nanotechnology
Telmo O. Paiva, Albertus Viljoen, Thaina M. da Costa, Joan A. Geoghegan, Yves F. Dufrene
Summary: Attachment of Staphylococcus aureus to human skin corneocyte cells is mediated by bacterial cell-surface protein adhesins, including fibronectin-binding protein B (FnBPB). Using single-molecule experiments, it is demonstrated that FnBPB binds to corneodesmosin (CDSN) on atopic dermatitis patient corneocytes through a sophisticated two-site mechanism.
ACS NANOSCIENCE AU
(2023)