ß-Lactamases, 3rd Edition

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

Deadline for manuscript submissions: 16 June 2025 | Viewed by 6064

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

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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 (4 papers)

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Research

10 pages, 1665 KiB  
Article
One Health Approach to Study the Occurrence and Antimicrobial Resistance of Extended-Spectrum β-Lactamase- and Carbapenemase-Producing Escherichia coli and Klebsiella spp. in Urban Agriculture in Burkina Faso
by Fatimata Bintou Josiane Diarra, Isidore Juste Ouindgueta Bonkoungou, Zakaria Garba, Namwin Siourimè Somda, Djifahamaï Soma, Marguerite Edith Malatala Nikiema, Evariste Bako, Souleymane Sore, Natéwindé Sawadogo, Nicolas Barro and Kaisa Haukka
Microorganisms 2024, 12(11), 2170; https://doi.org/10.3390/microorganisms12112170 - 29 Oct 2024
Viewed by 1683
Abstract
Data on antimicrobial resistance in Burkina Faso’s agricultural sector is still limited. This study assessed the occurrence of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-Ec) and Klebsiella spp. (ESBL-K) in lettuce, environment, and gardeners’ stools in market gardens in Ouagadougou, Burkina [...] Read more.
Data on antimicrobial resistance in Burkina Faso’s agricultural sector is still limited. This study assessed the occurrence of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-Ec) and Klebsiella spp. (ESBL-K) in lettuce, environment, and gardeners’ stools in market gardens in Ouagadougou, Burkina Faso. A total of 356 samples were collected from three vegetable gardens (76 lettuce, 76 soil, 62 manure, 63 irrigation water, and 79 human stools). The ESBL-selective medium was used for initial selection of ESBL-producing bacteria, and the isolates were further identified using biochemical tests. An antibiotic susceptibility test was performed using the disk diffusion method. The overall prevalence of ESBL-Ec and/or ESBL-K in the samples was 232/356 (65.2%). Of the lettuce samples, the prevalence of ESBL-Ec was 19/76 (25.0%) and ESBL-K 33/76 (43.4%). In the market gardens environment, the prevalence of ESBL-Ec was 32/201 (15.9%) and ESBL-K 124/201 (61.7%). In the gardeners’ stools, the prevalence of ESBL-Ec was 42/79 (53.2%) and ESBL-K 24/79 (30.4%). Two ESBL-K isolates were found to produce NDM carbapenemase. Due to the high prevalence of ESBL-producing bacteria, which may also be carbapenemase producers, it is necessary to monitor pathogens in agricultural products with a “One Health” approach to limit and prevent infections in the population. Full article
(This article belongs to the Special Issue ß-Lactamases, 3rd Edition)
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12 pages, 1545 KiB  
Article
Lippia origanoides and Thymus vulgaris Essential Oils Synergize with Ampicillin against Extended-Spectrum Beta-Lactamase-Producing Escherichia coli
by Levi Jafet Bastida-Ramírez, Leticia Buendía-González, Euridice Ladisu Mejía-Argueta, Antonio Sandoval-Cabrera, María Magdalena García-Fabila, Sergio Humberto Pavón-Romero, Monica Padua-Ahumada and Jonnathan Guadalupe Santillán-Benítez
Microorganisms 2024, 12(8), 1702; https://doi.org/10.3390/microorganisms12081702 - 17 Aug 2024
Viewed by 1340
Abstract
(1) Background: Could compounds such as monoterpenes and sesquiterpenes present in essential plant oils inhibit bacterial growth as an alternative to help mitigate bacterial resistance? The purpose of this study is evaluating the in vitro antibacterial effect of Lippia organoides EO (LEO) and [...] Read more.
(1) Background: Could compounds such as monoterpenes and sesquiterpenes present in essential plant oils inhibit bacterial growth as an alternative to help mitigate bacterial resistance? The purpose of this study is evaluating the in vitro antibacterial effect of Lippia organoides EO (LEO) and Thymus vulgaris EO (TEO), individually and in combination with ampicillin, against extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli strains; (2) Methods: Experimental in vitro design with post-test. The EOs were obtained by hydrodistillation and were analyzed by GC. ESBL-producing E. coli strains used were selected from urine cultures and the blaCTX-M and blaTEM resistance genes were identified by end point PCR. The disk diffusion method was used for the susceptibility tests. The MICs and MBCs were determined by microdilution test. Finally, the interaction effect was observed by checkerboard assay; (3) Results: A 39.9% decrease in the growth of the strain thymol in TEO and 70.4% in carvacrol in LEO was shown, observing inhibition halos of 32 mm for both EOs. MICs of 632 and 892 μg/mL for LEO and 738 and 940 μg/mL for TEO were determined. Finally, it was observed that, at low doses, there is a synergistic effect between TEO + LEO and EOs + ampicillin; (4) Conclusions: The findings demonstrate that TEO and LEO have an inhibitory effect on ESBL-producing E. coli, suggesting that they are candidates for further studies in the formulation of antibiotics to reduce bacterial resistance to traditional antibiotics. Full article
(This article belongs to the Special Issue ß-Lactamases, 3rd Edition)
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14 pages, 2704 KiB  
Article
Molecular, Genetic, and Biochemical Characterization of OXA-484 Carbapenemase, a Difficult-to-Detect R214G Variant of OXA-181
by Camille Gonzalez, Saoussen Oueslati, Mariam Rima, Réva Nermont, Laurent Dortet, Katie L. Hopkins, Bogdan I. Iorga, Rémy A. Bonnin and Thierry Naas
Microorganisms 2024, 12(7), 1391; https://doi.org/10.3390/microorganisms12071391 - 9 Jul 2024
Cited by 1 | Viewed by 1105
Abstract
OXA-244, an R214G variant of OXA-48, is silently spreading worldwide likely because of difficulties in detection using classical screening media. Here, we characterized two clinical isolates of Escherichia coli and Citrobacter youngae that displayed reduced susceptibility to carbapenems but were lacking significant carbapenemase [...] Read more.
OXA-244, an R214G variant of OXA-48, is silently spreading worldwide likely because of difficulties in detection using classical screening media. Here, we characterized two clinical isolates of Escherichia coli and Citrobacter youngae that displayed reduced susceptibility to carbapenems but were lacking significant carbapenemase activity as revealed by negative Carba NP test results. However, positive test results were seen for OXA-48-like enzymes by lateral flow immunoassays. WGS revealed the presence of a blaOXA-181-like gene that codes for OXA-484, an R214G variant of OXA-181. BlaOXA-484 gene was located on a 58.4-kb IncP1-like plasmid (pN-OXA-484), that upon transfer into E. coli HB4 with impaired permeability, conferred carbapenem and temocillin resistance (MICs > 32 mg/L). E. coli TOP10 (pTOPO-OXA-484) revealed reduced MICs in most substrates as compared to E. coli TOP10 (pTOPO-OXA-181), especially for imipenem (0.25 mg/L versus 0.75 mg/L) and temocillin (16 mg/L versus 1028 mg/L). Catalytic efficiencies of OXA-484 were reduced as compared to OXA-181 for most ß-lactams including imipenem and temocillin with 27.5- and 21.7-fold reduction, respectively. Molecular modeling confirmed that the salt bridges between R214, D159, and the R1 substituent’s carboxylate group of temocillin were not possible with G214 in OXA-484, explaining the reduced affinity for temocillin. In addition, changes in active site’s water network may explain the decrease in hydrolysis rate of carbapenems. OXA-484 has weak imipenem and temocillin hydrolytic activities, which may lead to silent spread due to underdetection using selective screening media or biochemical imipenem hydrolysis confirmatory tests. Full article
(This article belongs to the Special Issue ß-Lactamases, 3rd Edition)
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11 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://doi.org/10.3390/microorganisms12040805 - 16 Apr 2024
Viewed by 1285
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, 3rd Edition)
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