Alternative Approaches to Tackle Antibiotic Resistance in Tuberculosis (TB)

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Novel Antimicrobial Agents".

Deadline for manuscript submissions: 20 April 2024 | Viewed by 1979

Special Issue Editors

Mycobacteria Research Laboratory, Department of Biological Science, Institute of Structural and Molecular Biology, Birkbeck, University of London/UCL, Malet Street, London WC1E 7HX , UK
Interests: tuberculosis; antimicrobial drug resistance; target validation; new drug discovery; repurposing drugs
Special Issues, Collections and Topics in MDPI journals
Department of Infection Biology, The London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK
Interests: bacterial energy metabolism; target validation; antimicrobial resistance (AMR); infectious diseases
Special Issues, Collections and Topics in MDPI journals
Department of Microbial Diseases, UCL Eastman Dental Institute, University College London, London NW3 2PF, UK
Interests: antimicrobial resistance; metabolomics; transcriptomics; 3Rs; drug development

Special Issue Information

Dear Colleagues,

The COVID-19 pandemic has set back the progress made on antimicrobial resistance (AMR). It was recently reported that nearly 1.5 million people have died due to drug-resistant infections, and for the first time in a decade, there has been an increase in tuberculosis (TB)-related deaths. Without urgent re-focus, we risk slowing down drug discovery and the provision of new treatments for drug-resistant Mycobacterium tuberculosis (Mtb) and pathogenic non-tubercular mycobacteria (NTM). Unique in their immune evasion, dormancy, and resuscitation, the causal pathogens of TB and NTM have demonstrated extreme resistance to antibiotics. HIV-TB co-infections further exacerbate the TB epidemic, with more than 200,000 deaths occurring amongst HIV-positive patients every year. Therefore, the development of more efficient combination regimens must be urgently accelerated.  

In this Special Issue, we highlight international research that improves our ability to bring this universal goal closer to reality. We share examples of the application of modern technological advances that optimise high-throughput screening approaches, novel strategies to improve the hit rates of compounds that show promise in vitro and retain activity in the infected host environment, novel medicinal chemical approaches to identifying small-molecule inhibitors, and finally key progress in revealing new essential or virulence targets for pharmacological intervention through an improved understanding of the basic biological processes that different pathogens use to cause disease, among other topics. 

We invite manuscript submissions that further our understanding of antimicrobial resistance within the Mtb complex as well as infection caused by NTM and areas of leading research highlighting alternative approaches to tackling extensive drug resistance in the TB-causing bacilli. Submissions on investigative preclinical research outcomes considering the 3Rs (replacement, reduction, refinement) in laboratory practice are especially encouraged.

Prof. Dr. Sanjib Bhakta
Dr. Sam Willcocks
Dr. Dimitrios Evangelopoulos
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • tuberculosis
  • antibiotic resistance
  • 3Rs
  • Mycobacterium tuberculosis
  • non-tubercular mycobacteria/NTM
  • repurposing
  • alternative models and methods in drug discovery
  • accelerating drug development

Published Papers (1 paper)

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Research

15 pages, 4283 KiB  
Article
Antimicrobial Peptides Designed against the Ω-Loop of Class A β-Lactamases to Potentiate the Efficacy of β-Lactam Antibiotics
Antibiotics 2023, 12(3), 553; https://doi.org/10.3390/antibiotics12030553 - 10 Mar 2023
Cited by 1 | Viewed by 1696
Abstract
Class A serine β-lactamases (SBLs) have a conserved non-active site structural domain called the omega loop (Ω-loop), in which a glutamic acid residue is believed to be directly involved in the hydrolysis of β-lactam antibiotics by providing a water molecule during catalysis. We [...] Read more.
Class A serine β-lactamases (SBLs) have a conserved non-active site structural domain called the omega loop (Ω-loop), in which a glutamic acid residue is believed to be directly involved in the hydrolysis of β-lactam antibiotics by providing a water molecule during catalysis. We aimed to design and characterise potential pentapeptides to mask the function of the Ω-loop of β-lactamases and reduce their efficacy, along with potentiating the β-lactam antibiotics and eventually decreasing β-lactam resistance. Considering the Ω-loop sequence as a template, a group of pentapeptide models were designed, validated through docking, and synthesised using solid-phase peptide synthesis (SPPS). To check whether the β-lactamases (BLAs) were inhibited, we expressed specific BLAs (TEM-1 and SHV-14) and evaluated the trans-expression through a broth dilution method and an agar dilution method (HT-SPOTi). To further support our claim, we conducted a kinetic analysis of BLAs with the peptides and employed molecular dynamics (MD) simulations of peptides. The individual presence of six histidine-based peptides (TSHLH, ETHIH, ESRLH, ESHIH, ESRIH, and TYHLH) reduced β-lactam resistance in the strains harbouring BLAs. Subsequently, we found that the combinational effect of these peptides and β-lactams sensitised the bacteria towards the β-lactam drugs. We hypothesize that the antimicrobial peptides obtained might be considered among the novel inhibitors that can be used specifically against the Ω-loop of the β-lactamases. Full article
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