ß-Lactamases 3.0

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: 30 April 2024 | Viewed by 585

Special Issue Editor


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Guest Editor
School of Medicine, University Paris Saclay, Hopital de Bicêtre, Service de Bactériologie, Bâtiment Broca, 3ème étage, 78 rue du Gal Leclerc, 94275 Le Kremlin-Bicêtre, France
Interests: genetics of antibiotic resistance; gram negatives; ß-lactamases; carbapenemases; diagnostics (biochemical, phenotypical, molecular) and diagnostics of antibiotics resistance genes; NGS; transcriptomics; microbiota
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Special Issue Information

Dear Colleagues,

The discovery of antibiotics has revolutionized medicine by enabling the efficient treatment of many life-threatening bacterial infections. The fight against bacteria is turning again into one of the greatest challenges faced by our societies, especially with the spread of multidrug-resistant (MDR) bacteria. In some cases, resistance extends to the entire repertoire of available therapeutic agents (the so-called pan-drug-resistant phenotypes), posing a formidable challenge to antimicrobial therapy. This is an extremely worrying situation that brings us back to the pre-antibiotic era and thus threatens many achievements of modern medicine that rely on antibiotic therapies.

β-lactams are among the most prescribed antibiotics worldwide, mainly due to their weak toxicity and good efficacy. However, their clinical use is currently threatened by the worldwide spread of β-lactamases (BLs) capable of hydrolyzing them, especially among MDR Gram-negative bacteria (GNB). As the incidence of GNB infections for which few effective treatments are available increases, so does the contribution of drug-hydrolyzing enzymes such as β-lactamases to this serious clinical problem. Currently, β-lactamase-mediated resistance does not spare even the newest and most powerful β-lactams (carbapenems), whose activity is challenged by the class B metallo-β-lactamases (MBLs) (e.g., IMP, VIM, NDM) and the classes A and D serine-carbapenemases (e.g., KPC, IMI, GES, OXA-48, OXA-23, OXA-40).

The number of ß-lactamases being described has drastically increased (BLDB reference). They are either point mutant derivatives of well-known enzymes that may lead to modified hydrolysis profiles or to novel enzymes that are rarely described in human samples but may become a future problem. This large heterogeneity of enzymes illustrates the formidable potential of bacteria to adapt themselves to hostile environments and to fight against antibiotics.

This Special Issue is dedicated to all aspects of ß-lactamase research, with a special emphasis on the following topics:

  • Their presence in different fields (human, veterinarian and environmental samples);
  • Structure–function analysis;
  • Epidemiology;
  • The genetic basis at the origin of their dispersion (mobile genetic elements and plasmids);
  • The origin of ß-lactamase genes;
  • Unknown ß-lactamases present in metagenomic samples;
  • Novel drugs resistant to beta-lactamase hydrolysis and inhibitors.

Dr. Thierry Naas
Guest Editor

Manuscript Submission Information

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Keywords

  • ß-lactamases
  • multidrug-resistant bacteria
  • mobile genetic elements and plasmids
  • bacterial resistance
  • antibiotic therapies

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Published Papers (1 paper)

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Research

13 pages, 1340 KiB  
Article
In Silico Molecular Analysis of Carbapenemase-Negative Carbapenem-Resistant Pseudomonas aeruginosa Strains in Greece
by Katerina Tsilipounidaki, Christos-Georgios Gkountinoudis, Zoi Florou, George C. Fthenakis and Efthymia Petinaki
Microorganisms 2024, 12(4), 805; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms12040805 - 16 Apr 2024
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Abstract
To date, three carbapenem resistance mechanisms have been identified: carbapenemase released from the pathogen, changes in the expression of the outer membrane OprD porin, and overexpression of the efflux pump MexAB-OprM. Twelve carbapenemase-negative carbapenem-resistant Pseudomonas aeruginosa strains, isolated from patients hospitalized at the [...] Read more.
To date, three carbapenem resistance mechanisms have been identified: carbapenemase released from the pathogen, changes in the expression of the outer membrane OprD porin, and overexpression of the efflux pump MexAB-OprM. Twelve carbapenemase-negative carbapenem-resistant Pseudomonas aeruginosa strains, isolated from patients hospitalized at the University Hospital of Larissa, Central Greece, during 2023, which belonged to various sequence types (STs), were selected and were studied focusing on the characterization of their β-lactamases, on changes to OprD and its regulator MexT proteins, and on alterations to the MexAB-OprM regulator proteins encoded by the mexR, nalC, and nalD genes. Whole genome sequencing analysis revealed the presence of β-lactamase encoding genes, with blaPAO present in all isolates. Additionally, seven different genes of the oxacillinase family (blaOXA-35, blaOXA-50, blaOXA-395, blaOXA-396, blaOXA-486, blaOXA-488, blaOXA-494) were identified, with each strain harboring one to three of these. Regarding the OprD, five strains had truncated structures, at Loop 2, Loop 3, Loop 4, and Loop 9, while the remaining strains carried previously reported amino acid changes. Further, an additional strain had a truncated MexR; whereas, two other strains had totally modified NalC sequences. The active form of MexT, responsible for the downregulation of OprD production, as the intact sequence of the NalD protein, was found in all the strains studied. It is concluded that the truncated OprD, MexR, and NalC proteins, detected in eight strains, probably led to inactive proteins, contributing to carbapenem resistance. However, four strains carried known modifications in OprD, MexR, and NalC, as previously reported in both susceptible and resistant strains, a finding that indicates the complexity of carbapenem resistance in P. aeruginosa. Full article
(This article belongs to the Special Issue ß-Lactamases 3.0)
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