12 research outputs found
Molecular Characterisation of MDR Klebsiella pneumoniae and Escherichia coli isolates from Egypt containing Transferable Resistance to β-Lactam Antibiotics
No full textThe significant increase in antimicrobial resistance (AMR) over the past few years is a serious global public health concern, particularly in the developing countries, where infections with resistant organisms are associated with poor clinical reporting and higher cost burdens. The objectives of this research were to characterise multidrug-resistant (MDR) Klebsiella pneumoniae and Escherichia coli isolates from Egypt and evaluate the bacterial fitness associated with the acquisition of transferable, plasmid-based, resistance to β-Lactam antibiotics. A total of 169 MDR Enterobacteriaceae isolates from nosocomial and community-acquired infections were collected from 10 different university teaching hospitals on two surveillance studies and were divided into three groups (group 1: 65 K. pneumoniae from 2000-2003, and group 2: 63 K. pneumoniae from 2009-2011), and (group 3: 41 E. coli from 2009-2011). Phenotypic tests were performed according to CLSI 2013. Genotypic characterisation of blaCTX-M-15, blaOXA-48, and blaVIM distribution were performed by PCR and sequence analysis. The distribution of class 1 and class 2 integrons, and repeat-spacer CRISPR-Cas systems were analysed. Selected resistance plasmids transferability, stability and fitness were evaluated. An increase in multidrug resistance and class 1 integrons over time in the K. pneumoniae isolates was observed. A high prevalence of multidrug resistance, and class 1 and class 2 integrons were observed among the E. coli isolates. Types I-E* and IV-B CRISPR-Cas were detected among the isolates, showing hypervariability, and an inverse correlation with AMR prevalence. The transfer of certain β-Lactam resistance plasmids revealed that positive epistasis plays an important role in stabilising resistance within the analysed transconjugants. The new insights reveal the potential for the stable accumulation of β-lactam resistance and other antibiotic resistances over time in bacterial cells and the lower tendency for losing those resistances even in the absence of antibiotic pressure
Detection of new SHV-12, SHV-5 and SHV-2a variants of extended spectrum beta-lactamase in Klebsiella pneumoniae in Egypt.
No full textBACKGROUND: Klebsiella pneumoniae outbreaks possessing extended-spectrum β-lactamase- (ESBL) mediated resistance to third-generation cephalosporins have increased significantly in hospital and community settings worldwide. The study objective was to characterize prevalent genetic determinants of TEM, SHV and CTX-M types ESBL activity in K. pneumoniae isolates from Egypt. METHODS: Sixty five ESBL-producing K. pneumoniae strains, isolated from nosocomial and community-acquired infections from 10 Egyptian University hospitals (2000-2003), were confirmed with double disc-synergy method and E-test. blaTEM, blaSHV and blaCTX-m genes were identified by PCR and DNA sequencing. Pulsed-field gel electrophoresis (PFGE) was conducted for genotyping. RESULTS: All isolates displayed ceftazidime and cefotaxime resistance. blaTEM and blaSHV genes were detected in 98% of the isolates' genomes, while 11% carried blaCTX-m. DNA sequencing revealed plasmid-borne SHV-12,-5,-2a (17%), CTX-m-15 (11%), and TEM-1 (10%) prevalence. Among SHV-12 (n=8), one isolate displayed 100% blaSHV-12 amino acid identity, while others had various point mutations: T17G (Leu to Arg, position 6 of the enzyme: n=2); A8T and A10G (Tyr and Ile to Phe and Val, positions 3 and 4, respectively: n=4), and; A703G (Lys to Glu 235: n=1). SHV-5 and SHV-2a variants were identified in three isolates: T17G (n=1); A703G and G705A (Ser and Lys to Gly and Glu: n=1); multiple mutations at A8T, A10G, T17G, A703G and G705A (n=1). Remarkably, 57% of community-acquired isolates carried CTX-m-15. PFGE demonstrated four distinct genetic clusters, grouping strains of different genetic backgrounds. CONCLUSIONS: This is the first study demonstrating the occurrence of SHV-12, SHV-5 and SHV-2a variants in Egypt, indicating the spread of class A ESBL in K. pneumoniae through different mechanisms
a comprehensive review of assessment methods
No full textFunding Information: The author(s) declare that financial support was received for the research and/or publication of this article. This work is also supported by national funds through FCT/MCTES/FSE/UE, (doi: 10.54499/2023.01366.BD ) and Instituto Polit\u00E9cnico de Lisboa, national support through IPL/2022/InChildhealth/BI/12M; projects IPL/IDI&CA2024/WWTPSValor_ESTeSL and IPL/IDI&CA2024/MycoSOS_ESTeSL. This work was also supported by the Academy of Medical Sciences Springboard award Round 7 (SBF007\\100130). Funded by the European Union (grant agreement: 101056883). Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Health and Digital Executive Agency (HaDEA). Neither the European Union nor the granting authority can be held responsible for them. InChildHealth is also receiving funding from the Swiss State Secretariat for Education, Research and Innovation (SERI grant agreement 22.00324), from the United Kingdom Research and Innovation (UKRI grant agreement 10040524), and from the Australian National Health & Medical Research Council (NHMRC grant agreements APP2017786 and APP2008813). Publisher Copyright: Copyright © 2025 Cervantes, Pena, Riesenberger, Rodriguez, Henderson, Gonçalves, Newire, Pogner, Salonen, Almeida Silva, Ferguson, Haverinen-Shaughnessy and Viegas.This review addresses the increasing problem of fungal contamination in schools, which has a profound impact on indoor air quality and student health. Fungal contamination creates health problems such as respiratory problems, allergies, which can be particularly harmful in schools (e.g., Aspergillus fumigatus and Fusarium sp. are especially important as they are a well-known indoor allergens and can induce serious respiratory diseases). The aim of this study is to determine the effect of geographic location as well as season of filamentous fungi in school context. Through a comprehensive screening of 6,659 articles, 47 studies were selected for data extraction, detailing sampling techniques, analysis methods, climatic conditions, and relevant fungal species. The study highlights the importance of regularly measuring IAQ and utilizing both active and passive sampling methodologies in addition to molecular genetic analysis to complement identification and improve comparability across studies. A targeted monitoring is also proposed for species such as Aspergillus fumigatus (Aspergillus section Fumigati), Fusarium sp., and Mucorales order, which are therapeutically relevant, as well as Stachybotrys atra and Aspergillus section Flavi, in terms of their toxicological potential. Additionally, the article discusses the importance of consistent data formatting for effective meta-analysis and the need for further research to inform regulatory frameworks protecting student health. Recommendations for minimizing fungal threats include evaluating building structure, ventilation, cleaning practices, and gathering information from parents about school activities. Overall, the study underscores the global health risks posed by fungi in schools and calls for extensive investigations combining various sampling and analytical techniques. Additionally, the article discusses the importance of consistent data formatting for effective meta-analysis and the need for further research to inform regulatory frameworks protecting student health. Recommendations for minimizing fungal threats include evaluating building structure, ventilation, cleaning practices, and gathering information from parents about school activities. Overall, the study underscores the global health risks posed by fungi in schools and calls for extensive investigations combining various sampling and analytical techniques.publishersversionpublishe
Graduation Success For Students In Global Distance Learning Programme - 8 March 2011
No full textLONDON - Success was celebrated at the London School of Hygiene and Tropical Medicine with a pre-Graduation Day party for students from around the world who have been working for their degrees and diplomas in the School’s Distance Learning programme. Dean of Studies Sharon Huttly discusses the importance of having 2 800 students in the programme who live in 140 countries and who outnumber those studying in London. Students and graduates Araksya Hovhannesyan, Boris Rebac, Egwuonwu Chidoziem, Enas Newire, and Colin Meghoo tell their reasons for choosing distance learning; tutor Sue Stirling gives a flavour of the tutorial process conducted between staff and students physically located in different parts of the globe; James Ransom of the Commonwealth Scholarship Commission explains the reasons why his UK government-funded body is convinced of the benefits - both internationally and to the UK - of continuing to provide scholarships for able distance learners wherever they may live
Identification of a Type IV-A CRISPR-Cas System Located Exclusively on IncHI1B/IncFIB Plasmids in Enterobacteriaceae
No full textClustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are diverse immune systems found in many prokaryotic genomes that target invading foreign DNA such as bacteriophages and plasmids. There are multiple types of CRISPR with arguably the most enigmatic being Type IV. During an investigation of CRISPR carriage in clinical, multi-drug resistant, Klebsiella pneumoniae, a Type IV-A3 CRISPR-Cas system was detected on plasmids from two K. pneumoniae isolates from Egypt (isolated in 2002–2003) and a single K. pneumoniae isolate from the United Kingdom (isolated in 2017). Sequence analysis of all other genomes available in GenBank revealed that this CRISPR-Cas system was present on 28 other plasmids from various Enterobacteriaceae hosts and was never found on a bacterial chromosome. This system is exclusively located on IncHI1B/IncFIB plasmids and is associated with multiple putative transposable elements. Expression of the cas loci was confirmed in the available clinical isolates by RT-PCR. In all cases, the CRISPR-Cas system has a single CRISPR array (CRISPR1) upstream of the cas loci which has several, conserved, spacers which, amongst things, match regions within conjugal transfer genes of IncFIIK/IncFIB(K) plasmids. Our results reveal a Type IV-A3 CRISPR-Cas system exclusively located on IncHI1B/IncFIB plasmids in Enterobacteriaceae that is likely to be able to target IncFIIK/IncFIB(K) plasmids presumably facilitating intracellular, inter-plasmid competition
isolate from a reusable water bottle
No full textA re-usable water bottle was swabbed as part of the citizen science project Swab and Send and a Klebsiella grimontii isolate was recovered on chromogenic agar and designated SS141. Whole genome sequencing of SS141 showed it has the potential to be a human pathogen as it contains the biosynthetic gene cluster for the potent cytotoxin, kleboxymycin, and genes for other virulence factors. The genome also contains the antibiotic resistance genes blaOXY-6-4 and a variant of fosA which is likely to explain the observed resistance to ampicillin, amoxicillin and fosfomycin. We have also shown that SS141 forms biofilms on both polystyrene and polypropylene surfaces, providing a reasonable explanation for its ability to colonise a re-usable water bottle. With the increasing use of re-usable water bottles as an alternative to disposables, and a strong forecast for growth in this industry over the next decade, this study highlights the need for cleanliness comparable to other re-usable culinary items.</p
Mobile colistin resistance gene mcr-1 detected on an IncI1 plasmid in Escherichia coli from meat
No full textMobile colistin resistance (mcr) genes encoded on conjugative plasmids, although described only relatively recently, have been reported globally both in humans and livestock. The genes are often associated with the insertion sequence ISApl1 that can transpose the genes to novel genetic locations. Since its first report, multiple variants of mcr have been discovered in a variety of genetic locations in Escherichia coli, in plasmids and integrated into the chromosome.
(Ardig project
New Teixobactin Analogues with a Total Lactam Ring
No full textTeixobactin is a new antibiotic peptide with strong efficacy
against
several Gram-positive resistant bacteria, the structure of which
is extremely difficult to obtain in the laboratory via multistep conventional
synthesis. To face the increasing antibiotic resistant bacteria, it
is fundamental to introduce new types of antibiotics with innovative
mechanisms of action without resistance; thus, many scientists are
studying and developing new methods to synthesize teixobactin analogues.
In this work, seven Arg10-teixobactin analogues with a
total lactam ring have been prepared via solid phase peptide synthesis.
In order to obtain the total lactam ring, d-Thr8 was replaced by (2R,3S)-diamino-propionic
acid. To verify their antimicrobial activity and efficacy, each analogue
was tested with MIC against different resistant pathogens, showing
an interesting activity for Nle11 containing compounds
Mobile colistin resistance gene mcr-1 is detected on an Incl1 plasmid in E.coli from meat
No full textObjectives: Mobile colistin resistance (mcr) genes encoded on conjugative plasmids, although described only relatively recently, have been reported globally both in humans and livestock. The genes are often associated with the insertion sequence ISApl1 that can transpose the genes to novel genetic locations. Since its first report, multiple variants of mcr have been discovered in a variety of genetic locations in Escherichia coli, in plasmids and integrated into the chromosome.Methods: Using hybrid assembly of short-read and long-read whole-genome sequencing data, the presence ofmcr-1 was confirmed on an IncI1 plasmid in E. coli. In vitro conjugation assays were performed to determine the potential to transfer between strains. Genetic comparison with previously reported IncI1 plasmids was performed.Results: The genomic sequence identified thatmcr-1 is present on a complete IncI1 plasmid. Comparison with previously reported extended-spectrum β-lactamase (ESBL)-encoding plasmids from E. coli in the Netherlands from the same time period indicated a distinct lineage for this plasmid.Conclusions: The observation ofmcr-1 on an IncI1 plasmid confirms that the genetic region of this gene is actively transposed between genetic locations. This active transposition has consequences for the study of the epidemiology of mcr in populations
Novltex: a new class of antibiotics with potent activity against multidrug-resistant bacterial pathogens─design, synthesis, and biological evaluation
No full textIncreasing spread of multidrug-resistant (MDR) bacteria demands antibiotics that combine potent activity with scalable synthesis. Novo29 (clovibactin) is promising but suffers from low yield (1%), dependence on costly and noncommercial d-hydroxy-asparagine (d-Hyn5), and lengthy syntheses. We report “Novltex”, a novel class of antibiotic that fuses the Leu10-teixobactin macrocycle to the Novo29 N-terminus tail, replacing d-Hyn5with inexpensive threonine. Our efficient synthesis delivers 30% yield with faster coupling cycles (∼10 min), enabling rapid and low-cost scale-up. A 16-member analogue library systematically probing amino-acid configuration identified analogue 4 (d-Leu2) as the initial lead, informing the rational design of analogue 12 (d-cyclohexylalanine2). Analogue 12 displays potent antibacterial activity (minimum inhibitory concentration (MIC) 0.12–0.5 μg/mL) against World Health Organization (WHO)-priority pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium, surpassing several licensed antibiotics while maintaining an excellent safety profile. Lipid II-binding assays confirm the conservation of the parent mechanism. Novltex, therefore, offers a practical, high-yielding, and cost-efficient platform for the development of next-generation antibiotics targeting MDR infections.</p
