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

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 12327

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Dr. Thierry Naas

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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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Dr. Rémy A. Bonnin

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Team Resist, UMR-1184 (INSERM—Université Paris-Saclay—CEA), LabEx Lermit, Faculty of Medicine, Le Kremlin-Bicêtre, France
Interests: genetic; genomics; epidemiology; antibiotic resistance; acinetobacter; enterobacterales; horizontal gene transfer
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Dr. Laura Dabos

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Evolutionary Systems Genetics of Microbes Lab, Centro de Biotecnología y Genómica de Plantas, Universidad Politécnica de Madrid, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Madrid, Spain
Interests: antibiotic resistance; evolution of beta-lactamases; biochemistry and structure of carbapenemases; molecular biology; CRISPR-Cas9
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

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;
Epidemiology;
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
Dr. Rémy A. Bonnin
Dr. Laura Dabos
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. 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 2700 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.

Related Special Issue

ß-Lactamases 3.0 in Microorganisms (1 article)

Published Papers (8 papers)

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Research

7 pages, 961 KiB

Open AccessCommunication

The Molecular Characterization of bla_NDM-1-Positive Acinetobacter baumannii Isolated in Central Greece

by Katerina Tsilipounidaki, Christos-George Gkountinoudis, Zoi Florou, George C. Fthenakis, Vivi Miriagou and Efthymia Petinaki

Microorganisms 2023, 11(10), 2588; https://doi.org/10.3390/microorganisms11102588 - 19 Oct 2023

Cited by 1 | Viewed by 845

Abstract

The objective of the present study is to report the detection and the molecular characterization of nine bla_NDM-1-positive Acinetobacter baumannii isolates, which were isolated from patients in a tertiary care hospital in Central Greece from December 2022 to August 2023. The isolates were characterized by whole genome sequencing to obtain Pasteur multilocus sequencing typing (MLST) and to identify the bla_NDM-1-environment, resistome, and virulence genes content. In silico MLST analysis showed that the isolates belonged to four different clones (STs 160, 2, 85, and 2493). All strains, apart from the bla_NDM-1-gene, possessed at least eight different genes, encoding resistance to various antimicrobial agents. Whole genome sequencing revealed two different structures of the bla_NDM-1 environment. The first, detected in ST160 strain, was identical with the Tn125, whereas the second, found in STs 2, 85, and 2493 was associated with Tn7382. To our knowledge, after a sole strain reported in 2016 and imported by a patient hospitalized in a Libyan hospital, this is the first report of the emergence of polyclonal bla_NDM-1-positive Acinetobacter baumannii in Greece. Our findings re-emphasize the need to apply diligent surveillance protocols in order to limit the horizontal transfer of the bla_NDM-1 gene to other A. baumannii clones or to other recipient strains. Full article

(This article belongs to the Special Issue ß-Lactamases 2.0)

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7 pages, 597 KiB

Open AccessCommunication

First Detection and Molecular Characterization of Pseudomonas aeruginosa bla_NDM-1 ST308 in Greece

by Katerina Tsilipounidaki, Christos-George Gkountinoudis, Zoi Florou, George C. Fthenakis, Vivi Miriagou and Efthymia Petinaki

Microorganisms 2023, 11(9), 2159; https://doi.org/10.3390/microorganisms11092159 - 26 Aug 2023

Cited by 2 | Viewed by 1165

Abstract

The objective of the present study is to report the detection and the molecular characterization of nine bla_NDM-1-positive Pseudomonas aeruginosa isolates, all of which belonged to the epidemic high-risk international clone ST308, and all were isolated from patients in a tertiary care hospital in Central Greece from May to July 2023.The isolates were characterized by whole genome sequencing to obtain multi-locus sequencing typing (MLST) and identify the bla_NDM1-environment and resistome and virulence genes content. In silico MLST analysis showed that all isolates belonged to the high-risk ST308 international clone. All strains possessed 22 different genes, encoding resistance to various antimicrobial agents. Whole genome sequencing revealed that the bla_NDM-1 was chromosomally located within the integrative and conjugative element ICE_Tn43716385 and that it was part of one cassette along with two other resistance genes, floR and msrE. Two additional resistance cassettes were also found in the genome, which included the arrays of aph(6)-Id, aph(3″)-Ib, floR, sul2 and aadA10, qnrVC1, aac(3)-Id, dfrB5, aac(6′)-II. Additionally, the strains possessed various virulence genes, e.g., aprA, exoU, lasA, lasB, toxA, and estA. All of the isolates shared identical genomes, which showed 98% similarity with the P. aeruginosa ST308 genome (acc. no CP020703), previously reported from Singapore. To our knowledge, this is the first report of ST308 bla_NDM-1-positive P. aeruginosa isolation in Europe, which indicates the transmission dynamics of this high-risk clone. Full article

(This article belongs to the Special Issue ß-Lactamases 2.0)

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14 pages, 3120 KiB

Open AccessArticle

Comparative Genomic Analysis of ST131 Subclade C2 of ESBL-Producing E. coli Isolates from Patients with Recurrent and Sporadic Urinary Tract Infections

by Daniel Jaén-Luchoro, Arezou Kahnamouei, Shora Yazdanshenas, Anna Lindblom, Emma Samuelsson, Christina Åhrén and Nahid Karami

Microorganisms 2023, 11(7), 1622; https://doi.org/10.3390/microorganisms11071622 - 21 Jun 2023

Cited by 1 | Viewed by 1262

Abstract

The global emergence of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-E. coli), mainly causing urinary tract infections (UTI), is a major threat to human health. ESBL-E. coli sequence type (ST) 131 is the dominating clone worldwide, especially its subclade C2. Patients developing recurrent UTI (RUTI) due to ST131 subclade C2 appear to have an increased risk of recurrent infections. We have thus compared the whole genome of ST131 subclade C2 isolates from 14 patients with RUTI to those from 14 patients with sporadic UTI (SUTI). We aimed to elucidate if isolates causing RUTI can be associated with specific genomic features. Paired isolates from patients with RUTI were identical, presenting 2-18 single nucleotide polymorphism (SNP) differences for all six patients investigated. Comparative genomic analyses, including virulence factors, antibiotic resistance, pangenome and SNP analyses did not find any pattern associated with isolates causing RUTI. Despite extensive whole genome analyses, an increased risk of recurrences seen in patients with UTI due to ST131 subclade C2 isolates could not be explained by bacterial genetic differences in the two groups of isolates. Hence, additional factors that could aid in identifying bacterial properties contributing to the increased risk of RUTI due to ESBL-E. coli ST131 subclade C2 remains to be explored. Full article

(This article belongs to the Special Issue ß-Lactamases 2.0)

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10 pages, 2014 KiB

Open AccessCommunication

Molecular Evolutionary Analyses of the Pseudomonas-Derived Cephalosporinase Gene

by Tatsuya Shirai, Mao Akagawa, Miho Makino, Manami Ishii, Ayaka Arai, Norika Nagasawa, Mitsuru Sada, Ryusuke Kimura, Kaori Okayama, Taisei Ishioka, Haruyuki Ishii, Shinichiro Hirai, Akihide Ryo, Haruyoshi Tomita and Hirokazu Kimura

Microorganisms 2023, 11(3), 635; https://doi.org/10.3390/microorganisms11030635 - 01 Mar 2023

Viewed by 1557

Abstract

Despite the increasing evidence of the clinical impact of Pseudomonas-derived cephalosporinase (PDC) sequence polymorphisms, the molecular evolution of its encoding gene, bla_PDC, remains elusive. To elucidate this, we performed a comprehensive evolutionary analysis of bla_PDC. A Bayesian Markov Chain Monte Carlo phylogenetic tree revealed that a common ancestor of bla_PDC diverged approximately 4660 years ago, leading to the formation of eight clonal variants (clusters A–H). The phylogenetic distances within clusters A to G were short, whereas those within cluster H were relatively long. Two positive selection sites and many negative selection sites were estimated. Two PDC active sites overlapped with negative selection sites. In docking simulation models based on samples selected from clusters A and H, piperacillin was bound to the serine and the threonine residues of the PDC active sites, with the same binding mode for both models. These results suggest that, in P. aeruginosa, bla_PDC is highly conserved, and PDC exhibits similar antibiotic resistance functionality regardless of its genotype. Full article

(This article belongs to the Special Issue ß-Lactamases 2.0)

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7 pages, 1040 KiB

Open AccessCommunication

Diversity of Bacterial Clones and Plasmids of NDM-1 Producing Escherichia coli Clinical Isolates in Central Greece

by Katerina Tsilipounidaki, Zoi Florou, Anargyros Skoulakis, George C. Fthenakis, Vivi Miriagou and Efthymia Petinaki

Microorganisms 2023, 11(2), 516; https://doi.org/10.3390/microorganisms11020516 - 17 Feb 2023

Cited by 4 | Viewed by 1582

Abstract

The objective of the present study was to genetically characterize ten NDM-1 producing Escherichia coli isolates, recovered from patients in a hospital in Central Greece during the period 2017 to 2021.The isolates were studied by whole genome sequencing to obtain multi-locus sequencing typing (MLST), identification of bla_NDM1-environment, resistome and plasmid content. MLST analysis showed the presence of eight sequence types: ST46* (two isolates), ST46, ST744, ST998, ST410, ST224, ST4380, ST683 and ST12 (one isolate each). Apart of the presence of bla_NDM-1, the isolates carried a combination of various to β-lactams encoding resistance genes: bla_TEM-1B, bla_CTX-15, bla_OXA-1, bla_VIM-1, bla_SHV-5, bla_OXA-16, bla_OXA-10 and bla_VEB-1. Additionally, plurality of resistance genes to aminoglycosides, macrolides, rifamycin, phenicols, sulfonamides and tetracycline was detected. The presence of multiple replicons was observed, with predominance of IncFII and IncFIB. Analysis of bla_NDM-1 genetic environment of the isolates showed that seven had 100% identity with the pS-3002cz plasmid (Accession Number KJ 958927), two with the pB-3002cz plasmid (Accession Number KJ958926) and one with the pEc19397-131 plasmid (Accession Number MG878866). Τhis latter plasmid was derived by the fusion of two, previously identified, plasmids, pAMPD2 and pLK75 (Accession Numbers CP078058 and KJ440076, respectively). The diversity of clones and plasmids of NDM-1 producing E. coli isolated from patients in Greece indicates a continuous horizontal gene transfer. Full article

(This article belongs to the Special Issue ß-Lactamases 2.0)

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11 pages, 1345 KiB

Open AccessArticle

Molecular Epidemiology of Multidrug-Resistant Pseudomonas aeruginosa Acquired in a Spanish Intensive Care Unit: Using Diverse Typing Methods to Identify Clonal Types

by Marta Adelantado Lacasa, Maria Eugenia Portillo, Joaquin Lobo Palanco, Judith Chamorro and Carmen Ezpeleta Baquedano

Microorganisms 2022, 10(9), 1791; https://doi.org/10.3390/microorganisms10091791 - 06 Sep 2022

Cited by 1 | Viewed by 1705

Abstract

The increasing number of infections from multidrug-resistant P. aeruginosa (MDRPA) has compromised the selection of appropriate treatment in critically ill patients. Recent investigations have shown the existence of MDRPA global clones that have been disseminated in hospitals worldwide. We aimed to describe the molecular epidemiology and genetic diversity of the MDRPA acquired by Intensive Care Units (ICU) patients in our hospital. We used phenotypic methods to define the MDRPA and molecular methods were used to illustrate the presence of carbapenemase encoding genes. To characterize the MDRPA isolates, we used MALDI-TOF biomarker peaks, O-antigen serotyping, and multi-locus sequence typing analyses. Our data show that the most widely distributed MDRPA clone in our ICU unit was the ST175 strain. These isolates were further investigated by the whole-genome sequencing technique to determine the resistome profile and phylogenetic relationships, which showed, as previously described, that the MDR profile was due to the intrinsic resistance mechanisms and not the carbapenemase encoding genes. In addition, this study suggests that the combination of environmental focus and cross-transmission are responsible for the spread of MDRPA clones within our ICU unit. Serotyping and MALDI-TOF analyses are useful tools for the early detection of the most prevalent MDRPA clones in our hospital. Using these methods, semi-directed treatments can be introduced at earlier stages and healthcare professionals can actively search for environmental foci as possible sources of outbreaks. Full article

(This article belongs to the Special Issue ß-Lactamases 2.0)

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10 pages, 977 KiB

Open AccessEditor’s ChoiceArticle

Whole Genome Sequencing and Molecular Analysis of Carbapenemase-Producing Escherichia coli from Intestinal Carriage in Elderly Inpatients

by Maria Giufrè, Giulia Errico, Monica Monaco, Maria Del Grosso, Michela Sabbatucci, Annalisa Pantosti, Marina Cerquetti, Michela Pagnotta, Manuela Marra, Maria Carollo, Angelo Rossini, Elena Fogato, Elisabetta Cesana, Flaminia Gentiloni Silverj, Dorjan Zabzuni and Marco Tinelli

Microorganisms 2022, 10(8), 1561; https://doi.org/10.3390/microorganisms10081561 - 03 Aug 2022

Cited by 4 | Viewed by 1550

Abstract

The spread of carbapenemase-producing (CP) Enterobacterales is currently a worldwide concern, especially in the elderly. Twelve CP-E. coli isolated from rectal swabs of colonized inpatients aged ≥65 years from four hospitals in two Italian cities (Milan and Rome) were analyzed by whole genome sequencing (WGS) to obtain multi-locus sequence typing (MLST), identification of carbapenemase-encoding genes, resistome, plasmid content, and virulence genes. MLST analysis showed the presence of 10 unrelated lineages: ST410 (three isolates from three different hospitals in two cities) and ST12, ST38, ST69, ST95, ST131, ST189, ST648, ST1288, and ST1598 (one isolate each). Most isolates (9/12, 75%) contained a serine-β-lactamase gene (5 bla_KPC-3, 2 bla_KPC-2, and 2 bla_OXA-181), while three isolates harbored a metallo-β-lactamase gene (two bla_NDM-5 and one bla_VIM-1). In most CP-E. coli, the presence of more than one plasmid was observed, with the predominance of IncF. Several virulence genes were detected. All isolates contained genes enhancing the bacterial fitness, such as gad and terC, and all isolates but one, fimH, encoding type 1 fimbriae. In conclusion, CP-E. coli clones colonizing elderly patients showed heterogeneous genetic backgrounds. We recommend strict surveillance to monitor and prevent the spread of successful, high-risk clones in healthcare settings. Full article

(This article belongs to the Special Issue ß-Lactamases 2.0)

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9 pages, 573 KiB

Open AccessArticle

Screening and Characterization of Multidrug-Resistant Enterobacterales among Hospitalized Patients in the African Archipelago of Cape Verde

by Samanta Freire, Teresa Grilo, Maria Luísa Teixeira, Euclides Fernandes, Laurent Poirel and Marta Aires-de-Sousa

Microorganisms 2022, 10(7), 1426; https://doi.org/10.3390/microorganisms10071426 - 14 Jul 2022

Cited by 3 | Viewed by 1494

Abstract

This study aimed to investigate, for the first time, the occurrence and characteristics of extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing Enterobacterales in Cape Verde. A total of 98 inpatients hospitalized at Hospital Universitário Agostinho Neto were screened for rectal colonization. All ESBL- and carbapenemase-producing isolates were tested for antimicrobial susceptibility and characterized by multilocus sequence typing. Mating-out assay followed by PCR-based replicon typing were performed to characterize the plasmids harboring carbapenemase encoding genes. A large proportion of patients carried ESBL- or carbapenemase-producing Enterobacterales (56% and 6%, respectively). Among 93 ESBL-producing isolates, there were mainly Klebsiella pneumoniae (58%) and Escherichia coli (37%). Five different ESBLs were detected, with CTX-M-15 being highly predominant (92%). Six carbapenemase-producing isolates (five E. coli and one K. pneumoniae) were recovered, and all of the OXA-48-like type (four OXA-181, one OXA-48, and one OXA-244). The bla_OXA-48 gene was located on an IncFI-type plasmid, the bla_OXA-181 gene on IncFI or IncX3 plasmids, and the bla_OXA-244 gene was found to be chromosomally located. The five carbapenemase-producing E. coli isolates belonged to five distinct sequence types. This study overall showed a very high prevalence of ESBL-producing Enterobacterales, as well as the emergence of carbapenemase producers in this hospital. Full article

(This article belongs to the Special Issue ß-Lactamases 2.0)

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