Special Issue "ß-Lactamases"
Deadline for manuscript submissions: 31 December 2021.
Interests: genetics of antibiotic resistance; Gram negatives; ß-lactamases; carbapenemases; diagnostics (biochemical, phenotypical, molecular) and diagnostics of antibiotics resistance genes; NGS; transcriptomics; microbiota
Interests: carbapenemase producing Enterobacterales; Epidemiology and genomics of Acinetobacter spp.; colistin resistance; mobile genetic elements
Special Issues and Collections in MDPI journals
Interests: microbiology; PCR; gel electrophoresis; cloning
The discovery of antibiotics has revolutionized medicine by enabling 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, the 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 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, 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 special emphasis on:
- Their presence in different compartments (human, veterinarian and environmental samples);
- Structure–function analysis;
- 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
Assoc. Prof. Rémy A. Bonnin
Dr. Laura Dobos
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 papers will be 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. Microorganisms 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 2000 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.
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
1. Characterization of ESBL-producing Escherichia coli and Klebsiella pneumoniae isolated from clinical samples in a northern Portuguese hospital: predominance of CTX-M-15 and high genetic diversity
Abstract: Background: Enterobacteriaceae are major players in the spread of resistance to β-lactam antibiotics through the action of CTX-M β-lactamases. We aimed to analyze the diversity and genetic characteristics of ESBL-producing Escherichia coli and Klebsiella pneumoniae isolates from patients in a northern Portuguese hospital. Methods: A total of 62 cefotaxime/ceftazidime-resistant E. coli (n=38) and K. pneumoniae (n=24) clinical isolates were studied. Identification was performed by MALDI-TOF MS. Antimicrobial susceptibility testing against 13 antibiotics was performed. Detection of ESBL encoding resistance genes, phylogenetic grouping, and molecular typing (for selected isolates) was carried out by PCR/sequencing. Results: ESBL activity was detected in all 62 E. coli and K. pneumoniae isolates. Most of the ESBL-producing E. coli isolates carried a blaCTX-M gene (37/38 isolates), being blaCTX-M-15 predominant (n=32), although blaCTX-M-27 (n=1) and blaCTX-M-1 (n=1) were also detected. Two E. coli isolates carried the blaKPC2/3 gene. Regarding the 24 ESBL-producing K. pneumoniae isolates, 18 carried a blaCTX-M gene (blaCTX-M-15, 16 isolates; blaCTX-M-55, 2 isolates). All K. pneumoniae isolates carried blaSHV genes, including ESBL-variants (blaSHV-12, blaSHV-27, 14 isolates) or non-ESBL-variants (blaSHV-11, blaSHV-28, 10 isolates); Ten K. pneumoniae isolates also carried the blaKPC2/3 gene and showed imipenem-resistance. ESBL-positive E. coli isolates were ascribed to the B2 phylogenetic group (82%), mostly associated with ST131 lineage and, at a lower rate, to ST410/A. Regarding K. pneumoniae, the three international lineages ST15, ST147, and ST280 were detected among selected isolates. Conclusions: Different ESBL variants of CTX-M (especially CTX-M-15) and SHV-type (specially SHV-12) were detected among CTX/CAZR E. coli and K. pneumoniae isolates, in occasions associated with carbapenemases (blaKPC2/3 gene). Keywords: Antimicrobial resistance, Klebsiella pneumoniae, Escherichia coli, Public health, Car-bapenemases, β-lactamases, KPC2/3, CTX-M-15, human, Portugal
2. Title: CTX-M carrying plasmid identity in sequential E. coli isolates from patients with recurrent urinary tract infections.
Short summery: blaCTX-M (-14, -15 and -27)-carrying plasmids in various ESBL-E coli from patients with recurrent urinary tract infections (UTI) were analyzed for identity in 2-3 sequential isolates/patient using a new method, optical DNA-mapping combined with CRISPR/Cas9 (PMID: 27905467). Plasmids were strikingly identical in sequential ESBL-E coli isolated up to 6 months apart. Possible plasmid transfer between sequential ESBL-E.coli UTI-isolates was seen occasionally but appear to be very rare.
3. A comprehensive review on betalactamases and their role outside bacteria (archae, humans, viruses..)
4. An original article on betalactamases characterization in CPR
5. by Guest editors
6. by Guest editors
7. Old antibiotics are one more treatment option for bacterial infections
8. A mathematical and mutational genotype-phenotype analysis of TEM-beta-lactamase
Abstract: The TEM β-lactamase (BLs) are widespread in clinical isolates often conferring resistance to cephalosporins and β-lactamase-inhibitors (BLI), which are the mainstay of empiric therapy for infections by gram-negative bacteria. Single amino acid substitutions, so far not addressed by molecular diagnostics, can dramatically change the phenotype of TEMs.Applying mathematical modelling, we aimed to identify amino acid positions of diagnostic relevance, which were proofed by targeted mutagenesis and comprehensive testing of the MIC against broad panel of substrates and inhibitors. Twelve amino acid positions were identified as good candidates for molecular differentiation of the phenotype. In double-mutants, where ESBL- and BLI-resistance-related positions were combined, the ESBL phenotype manifested. A different phenotype was observed for some TEM alleles compared to the reference database.
9.Targeted molecular detection of nosocomial carbapenemase-producing gram-negative bacteria – on near- and distant-patient surfaces
Abstract: Background： Here, we describe an integrative method to detect carbapenemase-producing gram-negative bacteria (gn-Cp) on surfaces/fomites in the patient environment. For sampling, we examined patient rooms from different wards of a 1400-bed university hospital in Germany. From December 2018 to June 2020, we examined environmental samples from 28 patient rooms occupied with patients who were proven to be colonized with gn-Cp by rectal screening. Methods：Depending on the duration of the patient’s hospitalization, we took samples after 24 hours, 72 hours and one week. For sampling, we divided the patients´ environment into four parts and took samples from near- and extended patient areas. To obtain a representative bacterial swab from a larger surface, such as the patient cabinet, we used PolywipesTM (medical wire, Corsham, Wiltshire, UK). To enrich the bacteria within the wipe, we used CASO boullion (Merck KGaA, Germany). The bacterial DNA was isolated. Carbapenemase was detected with specific qPCR primers. Results ：With this culture- and molecular-based approach, we could control the effectiveness of cleaning and disinfection in everyday clinical practice. Therefore, we could track the spread of gn-Cp within the patient room. The number of positive detections fluctuated between 30.5 % (mean value positive results after 72 hours) and 35.2 % (after 24 hours and one week). Conclusion：The method used to detect multidrug-resistant bacteria in the environment of patients by using PolywipesTM is reliable and can therefore be used as an effective, new tool in hygiene and infection control.