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Antibiotics
Special Issues
Recent Advances in the Development of Beta-Lactamase Inhibitors
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Recent Advances in the Development of Beta-Lactamase Inhibitors

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Mechanism and Evolution of Antibiotic Resistance".

Deadline for manuscript submissions: closed (30 October 2022) | Viewed by 2113

Special Issue Editors

Dr. Cecilia Pozzi

E-Mail Website
Guest Editor
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, via Aldo Moro 2, 53100 Siena, Italy
Interests: X-ray crystallography; structural biology; β-lactamases; antibiotic resistance; bacterial thymidylate synthase; human thymidylate synthase; pteridine reductase; Heat shock protein 90 N-terminal domain; Hippo-pathway; 14-3-3; bioinorganic chemistry; ferritin; glutaminyl cyclase
Special Issues, Collections and Topics in MDPI journals
Dr. Giusy Tassone

E-Mail Website
Guest Editor
Department of Biotechnology, Chemistry, and Pharmacy, University of Siena, 53100 Siena, Italy
Interests: structural biology; X-ray crystallography; molecular modelling; β-lactamases; antibiotic resistance; heat shock protein 90 N-terminal domain; 14-3-3 proteins; bacterial thymidylate synthase; human thymidylate synthase; pteridine reductase; Hippo-pathway; bioinorganic chemistry; ferritin; glutaminyl cyclase

Special Issue Information

Dear Colleagues,

This Special Issue is focused on β-lactamases and, more specifically, on the prominent advances made in recent years on the development of molecules able to effectively block the activity of these enzymes to fight bacteria resistance to β-lactam antibiotics.

In bacteria, a major resistance mechanism to β-lactam antibiotics is the production of one or more β-lactamases. These enzymes are classified in two structurally and mechanistically unrelated families, serine-β-lactamases (SBLs; classes A, C, and D) and the metallo-β-lactamases (MBLs; class B). The interest in discovering novel inhibitors has recently been renewed to counter the threat from extended-spectrum β-lactamases (ESBLs) and carbapenemases which are not inhibited by the classical SBL inhibitors clavulanic acid and tazobactam. Recently, two novel BL inhibitors, the diazabicyclooctane (DBO) avibactam and the boronate vaborbactam, have been reported and are currently applied in clinic in combination with ceftazidime and meropenem, respectively. β-lactamases are a wide family of enzymes, thus, the development of effective pan-class inhibitors is particularly challenging.

This Special Issue features multidisciplinary research focused on serine and metallo-β-lactamases, aiming to provide novel insight on these key targets to counteract bacteria resistance to β-lactam antibiotics. The main topics covered by this Special Issue are the identification and characterization of BL enzymes, mechanistic and structural studies, and the identification and development of SBL and MBL inhibitors.

Dr. Cecilia Pozzi
Dr. Giusy Tassone
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • serine-β-lactamases
  • metallo-β-lactamases
  • resistance
  • β-lactam antibiotics
  • β-lactamase inhibitors
  • extended spectrum β-lactamases
  • carbapenemases

Published Papers (1 paper)

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Research

22 pages, 10046 KiB  
Article
Novel 1,2,3-Triazole-sulphadiazine-ZnO Hybrids as Potent Antimicrobial Agents against Carbapenem Resistant Bacteria
by Faizah S. Aljohani, Nadjet Rezki, Mohamed R. Aouad, Mohamed Hagar, Basant A. Bakr, Marwa M. Shaaban and Bassma H. Elwakil
Antibiotics 2022, 11(7), 916; https://doi.org/10.3390/antibiotics11070916 - 7 Jul 2022
Cited by 6 | Viewed by 1493
Abstract
Bacterial pneumonia is considered one of the most virulent diseases with high morbidity and mortality rates, especially in hospitalized patients. Moreover, bacterial resistance increased over the last decades which limited the therapy options to carbapenem antibiotics. Hence, the metallo-β-lactamase-producing bacteria were deliberated as [...] Read more.
Bacterial pneumonia is considered one of the most virulent diseases with high morbidity and mortality rates, especially in hospitalized patients. Moreover, bacterial resistance increased over the last decades which limited the therapy options to carbapenem antibiotics. Hence, the metallo-β-lactamase-producing bacteria were deliberated as the most deadly and ferocious infectious agents. Sulphadiazine-ZnO hybrids biological activity was explored in vitro and in vivo against metallo-β-lactamases (MBLs) producing Klebsiella pneumoniae. Docking studies against NDM-1 and IMP-1 MBLs revealed the superior activity of the 3a compound in inhibiting both MBLs enzymes in a valid reliable docking approach. The MBLs inhibition enzyme assay revealed the remarkable sulphadiazine-ZnO hybrids inhibitory effect against NDM-1 and IMP-1 MBLs. The tested compounds inhibited the enzymes both competitively and noncompetitively. Compound 3b-ZnO showed the highest antibacterial activity against the tested metallo-β-lactamase producers with an inhibition zone (IZ) diameter reaching 43 mm and a minimum inhibitory concentration (MIC) reaching 2 µg/mL. Sulphadiazine-ZnO hybrids were tested for their in vitro cytotoxicity in a normal lung cell line (BEAS-2Bs cell line). Higher cell viability was observed with 3b-ZnO. Biodistribution of the sulphadiazine-ZnO hybrids in the lungs of uninfected rats revealed that both [124I]3a-ZnO and [124I]3b-ZnO hybrids remained detectable within the rats’ lungs after 24 h of endotracheal aerosolization. Moreover, the residence duration in the lungs of [124I]3b-ZnO (t1/2 4.91 h) was 85.3%. The histopathological investigations confirmed that compound 3b-ZnO has significant activity in controlling bacterial pneumonia infection in rats. Full article
(This article belongs to the Special Issue Recent Advances in the Development of Beta-Lactamase Inhibitors)
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