scholarly journals Comprehensive genome data analysis establishes a triple whammy of carbapenemases, ICEs and multiple clinically-relevant bacteria

2019 ◽  
Author(s):  
João Botelho ◽  
Joana Mourão ◽  
Adam P. Roberts ◽  
Luísa Peixe
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Bacterial Species ◽  
Beta Lactamase ◽  
Bacterial Genomes ◽  
Genome Database ◽  
Integrative And Conjugative Elements ◽  
Encoding Genes ◽  
Clinically Relevant Bacteria

AbstractCarbapenemases inactivate most β-lactam antibiotics, including carbapenems and have been frequently reported among Enterobacteriaceae, Acinetobacter spp. and Pseudomonas spp. Traditionally, the horizontal gene transfer of carbapenemase encoding genes (CEGs) has been linked to plasmids. However, given that integrative and conjugative elements (ICEs) are possibly the most abundant conjugative elements among prokaryotes, we conducted an in-silico analysis to ascertain the likely role of ICEs in the spread of CEGs among all bacterial genomes (n=182,663). We detected 17,520 CEGs, of which 66 were located within putative ICEs among several bacterial species (including clinically-relevant bacteria as Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli). Most CEGs detected within ICEs belong to the IMP, NDM and SPM metallo-beta-lactamase families, and the serine beta-lactamase KPC and GES families. Different mechanisms were likely responsible for acquisition of these genes. The majority of CEG-bearing ICEs belong to the MPFG, MPFT and MPFF classes and often encode resistance to other antibiotics (e.g., aminoglycosides and fluoroquinolones). This study provides a snapshot of the different CEGs associated with ICEs among available bacterial genomes and sheds light on the underappreciated contribution of ICEs to the spread of carbapenem resistance globally.Author NotesAll supporting data has been provided within the article or through supplementary data files. Supplementary material is available with the online version of this article.Impact StatementCarbapenems are commonly used to treat severe infections in humans. Resistance is often mediated by carbapenemases. These enzymes degrade carbapenems and are frequently present in plasmids. Here, we demonstrate that common carbapenemase-encoding genes (CEGs) found in clinical isolates (e.g. blaKPC, blaGES, blaIMP, blaNDM, blaVIM) can also be located within integrative and conjugative elements (ICEs). CEG-bearing ICEs belong to three mating-pair formation families. These mobile elements may be particularly important in bacteria where plasmids do not seem to play a significant role in the spread of antibiotic resistance genes, as Pseudomonas spp. This study considerably expands the knowledge of the repertoire of CEGs-bearing ICEs among clinically-relevant bacterial pathogens, such as Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli.Data SummaryAll the bacterial genomes scanned in this study have been deposited previously in the National Center for Biotechnology Information genome database and are listed on the supplementary tables. The extracted 66 ICEs in fasta format and the outputs for the profile HMMs scanned on the 386 putative MGEs identified in this study are deposited on figshare at https://figshare.com/projects/_Comprehensive_genome_data_analysis_establishes_a_triple_whammy_of_carbapenemases_ICEs_and_multiple_clinically-relevant_bacteria/78369.

scholarly journals Comprehensive genome data analysis establishes a triple whammy of carbapenemases, ICEs and multiple clinically relevant bacteria

2020 ◽  
Vol 6 (10) ◽  
Author(s):  
João Botelho ◽  
Joana Mourão ◽  
Adam P. Roberts ◽  
Luísa Peixe
Keyword(s):  
Type Species ◽  
Bacterial Species ◽  
Carbapenem Resistance ◽  
Beta Lactamase ◽  
Bacterial Genomes ◽  
Content Type ◽  
Integrative And Conjugative Elements ◽  
Link Type ◽  
Genome Data Analysis ◽  
Clinically Relevant Bacteria

Carbapenemases inactivate most β-lactam antibiotics, including carbapenems, and have frequently been reported among Enterobacteriaceae , Acinetobacter spp. and Pseudomonas spp. Traditionally, the horizontal gene transfer of carbapenemase-encoding genes (CEGs) has been linked to plasmids. However, given that integrative and conjugative elements (ICEs) are possibly the most abundant conjugative elements among prokaryotes, we conducted an in silico analysis to ascertain the likely role of ICEs in the spread of CEGs among all bacterial genomes (n=182 663). We detected 17 520 CEGs, of which 66 were located within putative ICEs among several bacterial species (including clinically relevant bacteria, such as Pseudomonas aeruginosa , Klebsiella pneumoniae and Escherichia coli ). Most CEGs detected within ICEs belong to the IMP, NDM and SPM metallo-beta-lactamase families, and the serine beta-lactamase KPC and GES families. Different mechanisms were likely responsible for acquisition of these genes. The majority of CEG-bearing ICEs belong to the MPFG, MPFT and MPFF classes and often encode resistance to other antibiotics (e.g. aminoglycosides and fluoroquinolones). This study provides a snapshot of the different CEGs associated with ICEs among available bacterial genomes and sheds light on the underappreciated contribution of ICEs to the spread of carbapenem resistance globally.

scholarly journals Pharmacodynamic Profile of Ertapenem against Klebsiella pneumoniae and Escherichia coli in a Murine Thigh Model

2005 ◽  
Vol 49 (1) ◽  
pp. 276-280 ◽  
Author(s):  
Dana Maglio ◽  
Mary Anne Banevicius ◽  
Christina Sutherland ◽  
Chinedum Babalola ◽  
Charles H. Nightingale ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Bacterial Species ◽  
Resistance Mechanism ◽  
Infection Model ◽  
Beta Lactamase ◽  
Pharmacodynamic Parameter ◽  
Mean Values ◽  
Extended Spectrum Beta Lactamase ◽  
Pharmacodynamic Profile

ABSTRACT The pharmacodynamic profile of ertapenem was evaluated in a neutropenic mouse thigh infection model. Extended-spectrum beta-lactamase (ESBL)-positive and ESBL-negative clinical strains of Escherichia coli and Klebsiella pneumoniae were studied. MICs ranged from 0.0078 to 0.06 μg/ml with standard inoculum tests. Ertapenem doses were administered once to five times daily to achieve various exposures, reported as the percentage of the dosing interval that the concentration of free ertapenem was in excess of the MIC (%T>MICfree). Mean values for the static exposure and 80% maximally effective exposure (ED80) were 19% (range, 2 to 38%) and 33% (range, 13 to 65%) T>MICfree, respectively. Differences in exposure requirements based on the presence of an ESBL resistance mechanism or bacterial species were not evident. In addition, experiments using a 100-fold higher inoculum did not decrease the magnitude of the reduction in bacterial density from baseline achieved compared to lower-inoculum studies. The pharmacodynamic parameter of %T>MICfree correlated well with bactericidal activity for all isolates, and the static and ED80 exposures are consistent with those reported previously for carbapenems.

scholarly journals Detection of KPC in Acinetobacter spp. in Puerto Rico

2009 ◽  
Vol 54 (3) ◽  
pp. 1354-1357 ◽  
Author(s):  
Iraida E. Robledo ◽  
Edna E. Aquino ◽  
María I. Santé ◽  
Jorge L. Santana ◽  
Diana M. Otero ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Puerto Rico ◽  
Klebsiella Pneumoniae ◽  
Acinetobacter Calcoaceticus ◽  
Multidrug Resistant ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Novel Variant ◽  
Acinetobacter Spp

ABSTRACT During an island-wide PCR-based surveillance study of beta-lactam resistance in multidrug-resistant (MDR) Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter calcoaceticus-baumannii complex isolates obtained from 17 different hospitals, 10 KPC-positive Acinetobacter isolates were identified. DNA sequencing of the bla KPC gene identified KPC-2, -3, and -4 and a novel variant, KPC-10. This is the first report of a KPC-type beta-lactamase identified in Acinetobacter species.

scholarly journals Improving the Efficacy of Antimicrobials against Biofilm-Embedded Bacteria Using Bovine Hyaluronidase Azoximer (Longidaza®)

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1740
Author(s):  
Elena Trizna ◽  
Diana Baidamshina ◽  
Anna Gorshkova ◽  
Valentin Drucker ◽  
Mikhail Bogachev ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Immune System ◽  
Side Effects ◽  
Klebsiella Pneumoniae ◽  
Chronic Infection ◽  
Bacterial Species ◽  
Biofilm Bacteria ◽  
Biofilm Structure

While in a biofilm, bacteria are extremely resistant to both antimicrobials and the immune system, leading to the development of chronic infection. Here, we show that bovine hyaluronidase fused with a copolymer of 1,4-ethylenepiperazine N-oxide and (N-carboxymethyl) -1,4-ethylenepiperazinium bromide (Longidaza®) destroys both mono- and dual-species biofilms formed by various bacteria. After 4 h of treatment with 750 units of the enzyme, the residual biofilms of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae preserved about 50–70% of their initial mass. Biomasses of dual-species biofilms formed by S. aureus and the four latter species were reduced 1.5-fold after 24 h treatment, while the significant destruction of S. aureus–P. aeruginosa and S. aureus–K. pneumoniae was also observed after 4 h of treatment with Longidaza®. Furthermore, when applied in combination, Longidaza® increased the efficacy of various antimicrobials against biofilm-embedded bacteria, although with various increase-factor values depending on both the bacterial species and antimicrobials chosen. Taken together, our data indicate that Longidaza® destroys the biofilm structure, facilitating the penetration of antimicrobials through the biofilm, and in this way improving their efficacy, lowering the required dose and thus also potentially reducing the associated side effects.

scholarly journals Antibacterial activity of methanol extracts of the leaves of three medicinal plants against selected bacteria isolated from wounds of lymphoedema patients

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dereje Nigussie ◽  
Gail Davey ◽  
Belete Adefris Legesse ◽  
Abebaw Fekadu ◽  
Eyasu Makonnen
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antibacterial Activity ◽  
Medicinal Plants ◽  
Klebsiella Pneumoniae ◽  
Streptococcus Pyogenes ◽  
Bacterial Species ◽  
Wound Infections ◽  
Methanol Extracts

Abstract Background Patients with lymphoedema are at high risk of getting bacterial and fungal wound infections leading to acute inflammatory episodes associated with cellulitis and erysipelas. In Ethiopia, wound infections are traditionally treated with medicinal plants. Methods Agar well diffusion and colorimetric microdilution methods were used to determine the antibacterial activity of methanol extracts of the three medicinal plants against Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Shewanella alage, methicillin-resistant S. aureus ATCC®43300TM, Staphylococcus aureus ATCC25923, Escherichia coli ATCC25922, Klebsiella pneumoniae ATCC700603, and Pseudomonas aeruginosa ATCC37853. Results The methanol extract of L. inermis leaves showed high activity against all tested bacterial species, which was comparable to the standard drugs. Similarly, the extracts of A. indica showed activity against all tested species though at higher concentrations, and higher activity was recorded against Streptococcus pyogenes isolates at all concentrations. However, the extract of A. aspera showed the lowest activity against all tested species except Streptococcus pyogenes isolates. The lowest minimum inhibitory concentration (MIC) was recorded with the extract of L. inermis against E. coli isolate and S. aureus ATCC 25923. Conclusion Methanol extracts of L. inermis, A. indica, and A. aspera leaves exhibited antimicrobial activity against selected bacterial isolates involved in wound infections, of which the methanol extracts of L. inermis exhibited the highest activity. The results of the present study support the traditional use of plants against microbial infections, which could potentially be exploited for the treatment of wound infections associated with lymphoedema.

scholarly journals ICEs are the main reservoirs of the ciprofloxacin-modifying crpP gene in Pseudomonas aeruginosa

2020 ◽  
Author(s):  
João Botelho ◽  
Filipa Grosso ◽  
Luísa Peixe
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Direct Repeats ◽  
Bacterial Genomes ◽  
Genome Database ◽  
Integrative And Conjugative Elements ◽  
Data Files ◽  
Supplementary Material ◽  
Ciprofloxacin Resistance ◽  
Chromosomal Mutations ◽  
Sequence Types

AbstractThe ciprofloxacin-modifying crpP gene was recently identified in a plasmid isolated from a clinical Pseudomonas aeruginosa clinical isolate. Homologues of this gene were also identified in Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii. We set out to explore the mobile genetic elements involved in the acquisition and spread of this gene in publicly available and complete genomes of Pseudomonas. The crpP gene was identified only in P. aeruginosa, in more than half of the complete chromosomes (61.9%, n=133/215) belonging to 52 sequence types, of which the high-risk clone ST111 was the most frequent. We identified 136 crpP-harboring ICEs, with 93.4% belonging to the mating-pair formation G (MPFG) family. The ICEs were integrated at the end of a tRNALys gene and were all flanked by highly conserved 45-bp direct repeats. The core ICEome contains 26 genes (2.2% of all genes), which are present in 99% or more of the crpP-harboring ICEs. The most frequently encoded traits on these ICEs include replication, transcription, intracellular trafficking and cell motility. Our work reveals that ICEs are the main vectors promoting the dissemination of the ciprofloxacin-modifying crpP gene in P. aeruginosa.Author NotesAll supporting data has been provided within the article or through supplementary data files. Supplementary material is available with the online version of this article.Impact StatementA high proportion of Pseudomonas aeruginosa clinical isolates are resistant to ciprofloxacin. Resistance to this antibiotic is often mediated by chromosomal mutations, but recently horizontally transferred genes have been identified. We assessed the repartition of the ciprofloxacin-modifying crpP gene among Pseudomonas genomes and we characterized the mobile elements associated with its acquisition. We found that this gene is prevalent in P. aeruginosa and frequently associated with integrative and conjugative elements (ICEs). Importantly, we also identified highly conserved direct repeats that can be used to accurately delimit crpP-carrying ICEs in P. aeruginosa genomes.Data SummaryAll the bacterial genomes scanned in this study have been deposited previously in the National Center for Biotechnology Information genome database and are listed on the supplementary tables. The newick files used to create the trees in Figures 1 and 4 are deposited on figshare at https://figshare.com/projects/ICEs_are_the_main_reservoirs_of_the_ciprofloxacin-modifying_crpP_gene_in_Pseudomonas_aeruginosa/79308.

scholarly journals Distribution of Extended-Spectrum β-Lactamase (ESBL)-Encoding Genes among Multidrug-Resistant Gram-Negative Pathogens Collected from Three Different Countries

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 247
Author(s):  
Khaled S. M. Azab ◽  
Mohamed Ali Abdel-Rahman ◽  
Hussien H. El-Sheikh ◽  
Ehab Azab ◽  
Adil A. Gobouri ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Saudi Arabia ◽  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Gram Negative ◽  
Extended Spectrum ◽  
Resistant Strains ◽  
Encoding Genes

The incidence of Extended-spectrum β-lactamase (ESBL)-encoding genes (blaCTX-M and blaTEM) among Gram-negative multidrug-resistant pathogens collected from three different countries was investigated. Two hundred and ninety-two clinical isolates were collected from Egypt (n = 90), Saudi Arabia (n = 162), and Sudan (n = 40). Based on the antimicrobial sensitivity against 20 antimicrobial agents from 11 antibiotic classes, the most resistant strains were selected and identified using the Vitek2 system and 16S rRNA gene sequence analysis. A total of 85.6% of the isolates were found to be resistant to more than three antibiotic classes. The ratios of the multidrug-resistant strains for Egypt, Saudi Arabia, and Sudan were 74.4%, 90.1%, and 97.5%, respectively. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa showed inconstant resistance levels to the different classes of antibiotics. Escherichia coli and Klebsiella pneumoniae had the highest levels of resistance against macrolides followed by penicillins and cephalosporin, while Pseudomonas aeruginosa was most resistant to penicillins followed by classes that varied among different countries. The isolates were positive for the presence of the blaCTX-M and blaTEM genes. The blaCTX-M gene was the predominant gene in all isolates (100%), while blaTEM was detected in 66.7% of the selected isolates. This work highlights the detection of multidrug-resistant bacteria and resistant genes among different countries. We suggest that the medical authorities urgently implement antimicrobial surveillance plans and infection control policies for early detection and effective prevention of the rapid spread of these pathogens.

Антимікробна резистентність провідних збудників інфекцій сечових шляхів у Києві (Україна)

2017 ◽  
Vol 1 (2) ◽  
pp. 48-60
Author(s):  
A.G. Salmanov ◽  
A.V. Rudenko
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Staphylococcus Epidermidis ◽  
Klebsiella Oxytoca ◽  
Enterobacter Aerogenes ◽  
Enterobacter Cloacae ◽  
Proteus Vulgaris ◽  
Providencia Rettgeri ◽  
E Coli

Мета роботи — вивчити резистентність до антибіотиків бактеріальних збудників інфекцій сечових шляхів (ІСШ), виділених у пацієнтів урологічного стаціонару в м. Києві. Матеріали і методи. Досліджено 1612 штамів бактерій, виділених із сечі хворих з ІСШ (цистит, уретрит, пієлонефрит), госпіталізованих в урологічне відділення ДУ «Інститут урології НАМН України» у м. Києві протягом 2016 р. Серед пацієнтів переважали жінки — 1201 (74,5 %). Вік хворих становив від 17 до 74 років. Для збору даних використано медичну документацію лікарні. Мікробіологічні дослідження виконано у лабораторії мікробіології ДУ «Інститут урології НАМН України». Аналізували результати культурального дослідження зразків сечі, зібраних за наявності клінічних ознак ІСШ. Дослідження клінічного матеріалу та інтерпретацію отриманих результатів проводили загальноприйнятими методами. Вивчено чутливість уропатогенів до 31 антибіотика дискодифузійним методом відповідно до рекомендацій Інституту клінічних та лабораторних стандартів США (Clinical and Laboratory Standards Institute (CLSI)). Результати та обговорення. Аналіз мікробного спектра сечі виявив домінування серед уропатогенів штамів Escherichia coli (32,0 %), Enterococcus faecalis (19,5 %), Klebsiella pneumoniae (10,9 %), Staphylococcus epidermidis (8,9 %), S. haemolyticus (6,5 %) та Pseudomonas aeruginosa (6,4 %). Частка Enterococcus faecium, Enterobacter aerogenes і Streptococcus viridans становила відповідно 2,5, 2,2 і 1,6 %, Enterobacter cloacae, Klebsiella oxytoca, Acinetobacter baumannii, Proteus vulgaris та Providencia rettgeri — менше 1,0 %. У більшості випадків (69,7 %) мікроорганізми виділено у монокультурі, у решті випадків — у мікробних асоціа- ціях. Високу резистентність до тестованих антибіотиків виявили штами E. aerogenes (45,1 %), E. cloacae (45,7 %), E. faecium (40,9 %), E. faecalis (40,7 %), E. coli (39,9 %), P. aeruginosa (34,0 %), K. pneumoniae (28,6 %). Найбільш активними до уропатогенів були іміпенем (E. coli — 87,6 %, P. aeruginosa — 75,7 %, E. cloacae — 67,3 %, E. aerogenes — 72,6 %, K. pneumoniae — 93,2 %), меропенем (E. coli — 89,1 %, P. aeruginosa — 76,7 %, K. pneumoniae — 82,6 %), лефлоцин (E. coli — 74,5 %, ентерококи — 78,7 %, P. aeruginosa — 76,7 %, E. cloacae — 73,9 %, E. aerogenes — 80,4 %, K. pneumoniae — 83,5 %), амоксицилін/клавуланат (ентерококи — 84,6 %), фурагін (ентерококи — 82,6 %), цефоперазон (K. pneumoniae — 89,2 %, P. aeruginosa — 73,8 %), цефтріаксон (K. pneumoniae — 80,1 %). Висновки. Антибіотикорезистентність збудників ІСШ — важлива терапевтична проблема. Найбільшою активністю до уропатогенів характеризуються іміпенем, меропенем, лефлоцин, амоксицилін/ клавуланат, фурагін, цефоперазон, цефтріаксон, які можна розглядати як препарат вибору для призначення стартової терапії ІСШ. Необхідно здійснювати постійний моніторинг за резистентністю до дії антибіотиків. Політику використання антибіотиків у кожному стаціонарі слід визначати залежно від локальних даних щодо резистентності до протимікробних препаратів.

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