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New Drugs and Novel Strategies against Nontuberculous Mycobacteria 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 8108

Special Issue Editors


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Guest Editor
Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, Italy
Interests: mycobacteria; tuberculosis; infection diseases; early drug discovery; nontuberculous mycobacteria; Mycobacterium tuberculosis; Mycobacterium abscessus
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Guest Editor
Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, 119071 Moscow, Russia
Interests: synthesis of new compounds against Mycobacterium tuberculosis and Mycobacterium abscessus
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Special Issue Information

Dear Colleagues,

Nontuberculous mycobacteria (NTM) are opportunistic pathogens, causing pulmonary diseases largely in immunocompromised patients or patients with pre-existing lung conditions, such as bronchiectasis, chronic obstructive pulmonary disease, and cystic fibrosis (CF). The NTM incidence (3.3 to 22.6%) is growing in particular among CF patients worldwide. Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABSC) are the most commonly identified NTM species in CF individuals. Among NTM species, Mycobacterium abscessus is becoming the most rapidly emerging pathogen in CF centers around the world.

NTM lung disease treatment is challenging due to the long and often unsuccessful therapy. In FC patients, MABSC infection accelerates lung function decline more than other bacteria, including Pseudomonas aeruginosa and Burkholderia cepacia. CF patients with MABSC are more likely to require transplant or to die despite drug treatment. M. abscessus eradication is further complicated by the spread of drug-resistant strains. Consequently, the discovery of new drugs is vital for CF patients’ life. Increasing research and drug discovery efforts are mandatory to have significant therapeutic advances for NTM diseases.

With this issue, we would like to invite possible contributors that study new drugs and novel strategies against these emerging pathogens to write a research article or review.

Prof. Dr. Maria Rosalia Pasca
Dr. Laurent Chiarelli
Dr. Giulia Degiacomi
Dr. Vadim Makarov
Guest Editors

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Keywords

  • nontuberculous Mycobacteria
  • Mycobacterium abscessus
  • lung diseases
  • cystic fibrosis
  • new drugs
  • cellular targets
  • drug resistance
  • mechanism of action of new drugs
  • emerging bacterial pathogens
  • therapy

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Published Papers (2 papers)

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Review

14 pages, 925 KiB  
Review
Mycobacterium abscessus Infections in Cystic Fibrosis Individuals: A Review on Therapeutic Options
by Deborah Recchia, Giovanni Stelitano, Alessandro Stamilla, Damaris L. Gutierrez, Giulia Degiacomi, Laurent R. Chiarelli and Maria Rosalia Pasca
Int. J. Mol. Sci. 2023, 24(5), 4635; https://doi.org/10.3390/ijms24054635 - 27 Feb 2023
Cited by 16 | Viewed by 3071
Abstract
Mycobacterium abscessus is an opportunistic pathogen that mainly colonizes and infects cystic fibrosis patients’ lungs. M. abscessus is naturally resistant to many antibiotics such as rifamycin, tetracyclines and β-lactams. The current therapeutic regimens are not very effective and are mostly based on repurposed [...] Read more.
Mycobacterium abscessus is an opportunistic pathogen that mainly colonizes and infects cystic fibrosis patients’ lungs. M. abscessus is naturally resistant to many antibiotics such as rifamycin, tetracyclines and β-lactams. The current therapeutic regimens are not very effective and are mostly based on repurposed drugs used against Mycobacterium tuberculosis infections. Thus, new approaches and novel strategies are urgently needed. This review aims to provide an overview of the latest ongoing findings to fight M. abscessus infections by analyzing emerging and alternative treatments, novel drug delivery strategies, and innovative molecules. Full article
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21 pages, 10385 KiB  
Review
Fragment-Based Drug Discovery against Mycobacteria: The Success and Challenges
by Namdev S. Togre, Ana M. Vargas, Gunapati Bhargavi, Mohan Krishna Mallakuntla and Sangeeta Tiwari
Int. J. Mol. Sci. 2022, 23(18), 10669; https://doi.org/10.3390/ijms231810669 - 14 Sep 2022
Cited by 14 | Viewed by 4303
Abstract
The emergence of drug-resistant mycobacteria, including Mycobacterium tuberculosis (Mtb) and non-tuberculous mycobacteria (NTM), poses an increasing global threat that urgently demands the development of new potent anti-mycobacterial drugs. One of the approaches toward the identification of new drugs is fragment-based drug discovery (FBDD), [...] Read more.
The emergence of drug-resistant mycobacteria, including Mycobacterium tuberculosis (Mtb) and non-tuberculous mycobacteria (NTM), poses an increasing global threat that urgently demands the development of new potent anti-mycobacterial drugs. One of the approaches toward the identification of new drugs is fragment-based drug discovery (FBDD), which is the most ingenious among other drug discovery models, such as structure-based drug design (SBDD) and high-throughput screening. Specialized techniques, such as X-ray crystallography, nuclear magnetic resonance spectroscopy, and many others, are part of the drug discovery approach to combat the Mtb and NTM global menaces. Moreover, the primary drawbacks of traditional methods, such as the limited measurement of biomolecular toxicity and uncertain bioavailability evaluation, are successfully overcome by the FBDD approach. The current review focuses on the recognition of fragment-based drug discovery as a popular approach using virtual, computational, and biophysical methods to identify potent fragment molecules. FBDD focuses on designing optimal inhibitors against potential therapeutic targets of NTM and Mtb (PurC, ArgB, MmpL3, and TrmD). Additionally, we have elaborated on the challenges associated with the FBDD approach in the identification and development of novel compounds. Insights into the applications and overcoming the challenges of FBDD approaches will aid in the identification of potential therapeutic compounds to treat drug-sensitive and drug-resistant NTMs and Mtb infections. Full article
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