scholarly journals Metabolite Profiling of Malaysian Gracilaria edulis Reveals Eplerenone as Novel Antibacterial Compound for Drug Repurposing Against MDR Bacteria

2021 ◽  
Vol 12 ◽  
Author(s):  
Ali Asghar ◽  
Yong-Chiang Tan ◽  
Muhammad Shahid ◽  
Yoon-Yen Yow ◽  
Chandrajit Lahiri
Keyword(s):  
Antimicrobial Resistance ◽  
Chemical Constituents ◽  
Bacterial Species ◽  
Drug Repurposing ◽  
Role Playing ◽  
Preliminary Evaluation ◽  
Red Seaweed ◽  
Gracilaria Edulis ◽  
Ongoing Effort ◽  
Biochemical Compounds

With a continuous threat of antimicrobial resistance on human health worldwide, efforts for new alternatives are ongoing for the management of bacterial infectious diseases. Natural products of land and sea, being conceived to be having fewer side effects, pose themselves as a welcome relief. In this respect, we have taken a scaffolded approach to unearthing the almost unexplored chemical constituents of Malaysian red seaweed, Gracilaria edulis. Essentially, a preliminary evaluation of the ethyl acetate and acetone solvent extracts, among a series of six such, revealed potential antibacterial activity against six MDR species namely, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella enterica, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, and Bacillus subtilis. Detailed analyses of the inlying chemical constituents, through LC-MS and GC-MS chromatographic separation, revealed a library of metabolic compounds. These were led for further virtual screening against selected key role playing proteins in the virulence of the aforesaid bacteria. To this end, detailed predictive pharmacological analyses added up to reinforce Eplerenone as a natural alternative from the plethora of plausible bioactives. Our work adds the ongoing effort to re-discover and repurpose biochemical compounds to combat the antimicrobial resistance offered by the Gram-positive and the -negative bacterial species.

Clin-mNGS: Automated Pipeline for Pathogen Detection from Clinical Metagenomic Data

2020 ◽  
Vol 15 ◽  
Author(s):  
Akshatha Prasanna ◽  
Vidya Niranjan
Keyword(s):  
Antimicrobial Resistance ◽  
High Performance ◽  
Pathogen Detection ◽  
Bacterial Species ◽  
Workflow Management ◽  
Metagenomic Data ◽  
Antimicrobial Resistance Genes ◽  
Culture Independent ◽  
Automated Pipeline ◽  
User Friendly

Background: Since bacteria are the earliest known organisms, there has been significant interest in their variety and biology, most certainly concerning human health. Recent advances in Metagenomics sequencing (mNGS), a culture-independent sequencing technology have facilitated an accelerated development in clinical microbiology and our understanding of pathogens. Objective: For the implementation of mNGS in routine clinical practice to become feasible, a practical and scalable strategy for the study of mNGS data is essential. This study presents a robust automated pipeline to analyze clinical metagenomic data for pathogen identification and classification. Method: The proposed Clin-mNGS pipeline is an integrated, open-source, scalable, reproducible, and user-friendly framework scripted using the Snakemake workflow management software. The implementation avoids the hassle of manual installation and configuration of the multiple command-line tools and dependencies. The approach directly screens pathogens from clinical raw reads and generates consolidated reports for each sample. Results: The pipeline is demonstrated using publicly available data and is tested on a desktop Linux system and a High-performance cluster. The study compares variability in results from different tools and versions. The versions of the tools are made user modifiable. The pipeline results in quality check, filtered reads, host subtraction, assembled contigs, assembly metrics, relative abundances of bacterial species, antimicrobial resistance genes, plasmid finding, and virulence factors identification. The results obtained from the pipeline are evaluated based on sensitivity and positive predictive value. Conclusion: Clin-mNGS is an automated Snakemake pipeline validated for the analysis of microbial clinical metagenomics reads to perform taxonomic classification and antimicrobial resistance prediction.

scholarly journals Patient-Specific Predictive Antibiogram in Decision Support for Empiric Antibiotic Treatment

2020 ◽  
Vol 41 (S1) ◽  
pp. s521-s522
Author(s):  
Debarka Sengupta ◽  
Vaibhav Singh ◽  
Seema Singh ◽  
Dinesh Tewari ◽  
Mudit Kapoor ◽  
...  
Keyword(s):  
Machine Learning ◽  
Antimicrobial Resistance ◽  
Model Building ◽  
Medical Center ◽  
Bacterial Species ◽  
Model Performance ◽  
The United States ◽  
Patient Specific ◽  
Gradient Boosting ◽  
Comparative Performance

Background: The rising trend of antibiotic resistance imposes a heavy burden on healthcare both clinically and economically (US$55 billion), with 23,000 estimated annual deaths in the United States as well as increased length of stay and morbidity. Machine-learning–based methods have, of late, been used for leveraging patient’s clinical history and demographic information to predict antimicrobial resistance. We developed a machine-learning model ensemble that maximizes the accuracy of such a drug-sensitivity versus resistivity classification system compared to the existing best-practice methods. Methods: We first performed a comprehensive analysis of the association between infecting bacterial species and patient factors, including patient demographics, comorbidities, and certain healthcare-specific features. We leveraged the predictable nature of these complex associations to infer patient-specific antibiotic sensitivities. Various base-learners, including k-NN (k-nearest neighbors) and gradient boosting machine (GBM), were used to train an ensemble model for confident prediction of antimicrobial susceptibilities. Base learner selection and model performance evaluation was performed carefully using a variety of standard metrics, namely accuracy, precision, recall, F1 score, and Cohen κ. Results: For validating the performance on MIMIC-III database harboring deidentified clinical data of 53,423 distinct patient admissions between 2001 and 2012, in the intensive care units (ICUs) of the Beth Israel Deaconess Medical Center in Boston, Massachusetts. From ~11,000 positive cultures, we used 4 major specimen types namely urine, sputum, blood, and pus swab for evaluation of the model performance. Figure 1 shows the receiver operating characteristic (ROC) curves obtained for bloodstream infection cases upon model building and prediction on 70:30 split of the data. We received area under the curve (AUC) values of 0.88, 0.92, 0.92, and 0.94 for urine, sputum, blood, and pus swab samples, respectively. Figure 2 shows the comparative performance of our proposed method as well as some off-the-shelf classification algorithms. Conclusions: Highly accurate, patient-specific predictive antibiogram (PSPA) data can aid clinicians significantly in antibiotic recommendation in ICU, thereby accelerating patient recovery and curbing antimicrobial resistance.Funding: This study was supported by Circle of Life Healthcare Pvt. Ltd.Disclosures: None

Antimicrobial resistance in zoonotic bacteria: lessons learned from host-specific pathogens

2008 ◽  
Vol 9 (2) ◽  
pp. 177-186 ◽  
Author(s):  
Trudy M. Wassenaar ◽  
Peter Silley
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Species ◽  
Lessons Learned ◽  
Animal Host ◽  
Relative Contribution ◽  
Single Animal ◽  
Resistance Patterns ◽  
Animal Hosts ◽  
Zoonotic Bacteria ◽  
Selection Of

AbstractThe relative contribution of veterinary and human clinical treatments to the selection of antimicrobial resistance in zoonotic pathogens remains controversial. In this review, we consider bacterial pathogens that differ in host specificity and address their resistance profiles: pathogens that only occur in the human host, pathogens that are specific to particular food-producing animals and pathogens that occur in both host types. Compared with those pathogens restricted to a single animal host, pathogens found in both human and animal hosts appear to have higher incidences of resistance. However, the most urgent and severe resistance problems occur with pathogens exclusively infecting humans. Differences exist in the available genetic repertoire of a bacterial species and these are reflected in the observed resistance patterns; it is important to note that different bacterial species do not automatically result in similarly resistant populations when they undergo comparable selection in different host species. Thus, within a bacterial species, prevalence of resistance can differ between populations isolated from different hosts. For some species, fluctuations in dominant subpopulations, for instance particular serotypes, can be the most important factor determining resistance. The frequently expressed opinion that veterinary use of antimicrobials is at the heart of many resistance problems may be an oversimplification of the complex forces at play.

scholarly journals Antimicrobial Activity of Non-steroidal Anti-inflammatory Drugs on Biofilm: Current Evidence and Potential for Drug Repurposing

2021 ◽  
Vol 12 ◽  
Author(s):  
Rodrigo Cuiabano Paes Leme ◽  
Raquel Bandeira da Silva
Keyword(s):  
Bacterial Species ◽  
Drug Repurposing ◽  
Current Evidence ◽  
Pharmacokinetic Studies ◽  
Bacterial Populations ◽  
Human Pharmacokinetic ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

It has been demonstrated that some non-steroidal anti-inflammatory drugs (NSAIDs), like acetylsalicylic acid, diclofenac, and ibuprofen, have anti-biofilm activity in concentrations found in human pharmacokinetic studies, which could fuel an interest in repurposing these well tolerated drugs as adjunctive therapies for biofilm-related infections. Here we sought to review the currently available data on the anti-biofilm activity of NSAIDs and its relevance in a clinical context. We performed a systematic literature review to identify the most commonly tested NSAIDs drugs in the last 5 years, the bacterial species that have demonstrated to be responsive to their actions, and the emergence of resistance to these molecules. We found that most studies investigating NSAIDs’ activity against biofilms were in vitro, and frequently tested non-clinical bacterial isolates, which may not adequately represent the bacterial populations that cause clinically-relevant biofilm-related infections. Furthermore, studies concerning NSAIDs and antibiotic resistance are scarce, with divergent outcomes. Although the potential to use NSAIDs to control biofilm-related infections seems to be an exciting avenue, there is a paucity of studies that tested these drugs using appropriate in vivo models of biofilm infections or in controlled human clinical trials to support their repurposing as anti-biofilm agents.

scholarly journals Antimicrobial resistance of Klebsiella pneumoniae strains isolated from urine in hospital patients and outpatients

2021 ◽  
Vol 5 (1) ◽  
pp. 001-007
Author(s):  
Ostojic Maja ◽  
Hubana Mahir ◽  
Cvetnić Marija ◽  
Benić Miroslav ◽  
Cvetnić Zeljko
Keyword(s):  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Bacterial Species ◽  
Urine Samples ◽  
Klebsiella Pneumonia ◽  
Immunocompromised Patients ◽  
Therapeutic Results ◽  
Highly Effective ◽  
Hospital Patients ◽  
Almost All

Background: Klebsiella pneumoniae is a bacterial species that often causes infections in humans. Infections occur most frequently in hospitalised or immunocompromised patients and are treated with antimicrobials. In recent decades, K. pneumoniae has developed significant resistance to many antimicrobials. Objective: The main goal of this study was to determine the frequency of resistance of isolated K. pneumoniae strains from urine samples of hospital patients and outpatients, and to find evidence of ESBL strains and their resistance to certain antibiotics. Methods: During the study period, Klebsiella pneumonia was isolated from the urine samples of 430 patients. The procedure for processing of urine samples, identification, susceptibility toward antimicrobials and evidence of ESBL strains were carried out according to the recommended standards. Results: Of the total K. pneumoniae isolates, 153 (35.6%) were isolated from hospital patients and 277 (64.4%) from outpatients. Strains isolated from hospital patients were resistant to each tested antibiotic. ESBL strains were detected in 169 (39.30%) samples, 92 (60.13%) from hospital patients and 77 (27.8%) from outpatients. Conclusion: Strains of K. pneumoniae isolated from the urine of hospital patients and outpatients have developed significant resistance against all tested antibiotic substances. A higher occurrence of ESBL strains was observed in hospital patients than in outpatients. ESBL strains were resistant to all penicillins and almost all cephalosporins. Highly effective antimicrobials were amikacin, colistine, carbapenem and fosfomycin. The best therapeutic results were achieved when patients were treated with fosfomycin and imipenem.

scholarly journals Antimicrobial Susceptibility Testing and Tentative Epidemiological Cutoff Values for FiveBacillusSpecies Relevant for Use as Animal Feed Additives or for Plant Protection

2018 ◽  
Vol 84 (19) ◽  
Author(s):  
Yvonne Agersø ◽  
Birgitte Stuer-Lauridsen ◽  
Karin Bjerre ◽  
Michelle Geervliet Jensen ◽  
Eric Johansen ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Resistance Genes ◽  
Pathogenic Bacteria ◽  
Animal Feed ◽  
Bacterial Species ◽  
Feed Additives ◽  
Content Type ◽  
Cutoff Values ◽  
Antimicrobial Resistance Genes ◽  
Species Specific

ABSTRACTBacillus megaterium(n= 29),Bacillus velezensis(n= 26),Bacillus amyloliquefaciens(n= 6),Bacillus paralicheniformis(n= 28), andBacillus licheniformis(n= 35) strains from different sources, origins, and time periods were tested for the MICs for nine antimicrobial agents by the CLSI-recommended method (Mueller-Hinton broth, 35°C, for 18 to 20 h), as well as with a modified CLSI method (Iso-Sensitest [IST] broth, 37°C [35°C forB. megaterium], 24 h). This allows a proposal of species-specific epidemiological cutoff values (ECOFFs) for the interpretation of antimicrobial resistance in these species. MICs determined by the modified CLSI method were 2- to 16-fold higher than with the CLSI-recommended method for several antimicrobials. The MIC distributions differed between species for five of the nine antimicrobials. Consequently, use of the modified CLSI method and interpretation of resistance by use of species-specific ECOFFs is recommended. The genome sequences of all strains were determined and used for screening for resistance genes against the ResFinder database and for multilocus sequence typing. A putative chloramphenicol acetyltransferase (cat) gene was found in oneB. megateriumstrain with an elevated chloramphenicol MIC compared to the otherB. megateriumstrains. InB. velezensisandB. amyloliquefaciens, a putative tetracycline efflux gene,tet(L), was found in all strains (n= 27) with reduced tetracycline susceptibility but was absent in susceptible strains. AllB. paralicheniformisand 23% ofB. licheniformisstrains had elevated MICs for erythromycin and harboredermD. The presence of these resistance genes follows taxonomy suggesting they may be intrinsic rather than horizontally acquired. Reduced susceptibility to chloramphenicol, streptomycin, and clindamycin could not be explained in all species.IMPORTANCEWhen commercializing bacterial strains, likeBacillusspp., for feed applications or plant bioprotection, it is required that the strains are free of acquired antimicrobial resistance genes that could potentially spread to pathogenic bacteria, thereby adding to the pool of resistance genes that may cause treatment failures in humans or animals. Conversely, if antimicrobial resistance is intrinsic to a bacterial species, the risk of spreading horizontally to other bacteria is considered very low. Reliable susceptibility test methods and interpretation criteria at the species level are needed to accurately assess antimicrobial resistance levels. In the present study, tentative ECOFFs for fiveBacillusspecies were determined, and the results showed that the variation in MICs followed the respective species. Moreover, putative resistance genes, which were detected by whole-genome sequencing and suggested to be intrinsic rather that acquired, could explain the resistance phenotypes in most cases.

Skrining Fitokimia Enam Genotipe Teh

2014 ◽  
Vol 1 (2) ◽  
pp. 63
Author(s):  
Budi Martono ◽  
Rudi T. Setiyono
Keyword(s):  
Camellia Sinensis ◽  
Chemical Constituents ◽  
The Other ◽  
Preliminary Evaluation ◽  
Phytochemical Screening ◽  
Tea Leaves ◽  
Randomized Design ◽  
Medicinal Crops ◽  
Completely Randomized Design

<p>Skrining fitokimia dimaksudkan untuk melakukan evaluasi pendahuluan tentang kandungan kimia pada teh (Camellia sinensis). Selain itu, teh mengandung katekin yang dapat digunakan sebagai petunjuk kualitas dari daun teh. Penelitian bertujuan mengetahui kandungan senyawa aktif dan kadar katekin pada teh. Penelitian dilaksanakan mulai bulan April sampai dengan Juni 2012 di laboratorium Pengujian Balai Penelitian Tanaman Rempah dan Obat, Bogor. Skrining fitokimia pucuk peko dengan dua daun (p+2) dilakukan berdasarkan prosedur dari Materia Medika Indonesia (MMI), sedangkan analisis katekin dengan menggunakan metode SNI gambir. Penelitian disusun berdasarkan rancangan acak lengkap (RAL), enam perlakuan dengan empat ulangan. Perlakuan yang digunakan adalah enam genotipe teh (Tbs 1, Tbs 2, Hibrid, Cin 143, Rb 3, dan Kiara 8). Hasil penelitian menunjukkan keenam genotipe yang diuji mengandung senyawa alkaloid, saponin, tanin, fenolik, flavanoid, steroid, dan glikosida. Genotipe Tbs 1, Hibrid, dan Kiara 8 positif mengandung senyawa triterpenoid, sedangkan Tbs 2, Rb 3, dan Cin 143 negatif. Genotipe Tbs 1 dan Tbs 2 memiliki kandungan katekin paling tinggi (kecuali bagian ruas+tangkai daun) dibandingkan dengan empat genotipe lainnya. Pucuk peko, daun pertama, dan daun kedua pada genotipe Tbs 1 memiliki kadar katekin masing-masing 17,92%, 11,73%, dan 14,67%, sedangkan pada genotipe Tbs 2 masing-masing 18,22%, 13,48%, dan 15,81%. Kadar katekin terendah dihasilkan oleh bagian ruas+tangkai daun pada genotipe Rb 3 (1,78%). Pucuk peko menghasilkan kandungan katekin bervariasi antara 8,36%-18,22%, lebih tinggi dibandingkan dengan daun pertama, daun kedua, dan bagian ruas + tangkai daun.</p><p>Kata kunci: Camellia sinensis, fitokimia, genotipe, katekin, pucuk peko</p><p>Phytochemical screening was intended for a preliminary evaluation of the chemical constituents of the tea (Camellia sinensis). In addition, tea also contains catechin that can be used as an indication of the quality of tea leaves. The objectives of this study were to determine the content of the active compounds and catechin in tea. The research was conducted from April to June 2012 in the Laboratory of the Research Institute for Spices and Medicinal Crops, Bogor. The phytochemical screening was performed based on the procedure of Materia Medika Indonesia (MMI), while the catechin analysis used the method of SNI gambir. The study was carried out in completely randomized design with six treatments and four replications. The treatments used are six tea genotypes namely Tbs 1, Tbs 2, Hibrid, Cin 143, Rb 3, and Kiara 8. The results showed that the six tea genotypes tested contained the compounds of alkaloid, saponin, tannin, phenolic, flavanoid, steroid, and glycoside. Positively triterpenoid compounds present in the genotype of Tbs1, Hybrids, and Kiara 8, and negative in Tbs 2, Rb 3, and Cin 143. The genotypes of Tbs 1 and Tbs 2 produced the highest catechin content compared to the other genotypes. Catechin content was lowest in the part of internodes+leaf stalk of Rb 3 (1.78%). Pecco shoots produce catechin content of about 8.36%-18.22%, higher than the first leaf, second leaf, and the parts of internodes+leaf stalk.</p>

scholarly journals Update on drug-repurposing: is it useful for tackling antimicrobial resistance?

2019 ◽  
Vol 14 (10) ◽  
pp. 829-831 ◽  
Author(s):  
Grace Kaul ◽  
Manjulika Shukla ◽  
Arunava Dasgupta ◽  
Sidharth Chopra
Keyword(s):  
Antimicrobial Resistance ◽  
Drug Repurposing

scholarly journals Antimicrobial Resistance, an Update from the Ward: Increased Incidence of New Potential Pathogens and Site of Infection-Specific Antibacterial Resistances

Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 631
Author(s):  
Irene Stefanini ◽  
Martina Boni ◽  
Paola Silvaplana ◽  
Paola Lovera ◽  
Stefania Pelassa ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Species ◽  
University Hospital ◽  
Ecological Approach ◽  
The European Union ◽  
Bacterial Strains ◽  
General Observation ◽  
Source Type ◽  
Geographical Scale ◽  
Community Onset

In order to monitor the spread of antimicrobial resistance, the European Union requires hospitals to be equipped with infection control centers. With this aim, we analyzed 1583 bacterial strains isolated from samples of different origin from patients with community-onset and nosocomial infections in a public tertiary University Hospital on the outskirts of Turin, Italy. Statistical analyses of the isolates (source, type) and their antimicrobial resistance (AMR) were performed. The survey revealed infections associated with bacterial species considered as not-commensal and not-pathogenic, hence potentially emerging as new threats for human health. Conversely to the general observation of nosocomial strains being more resistant to antibiotics compared to community-acquired strains, nosocomial strains isolated in this study were more resistant only to 1/42 tested antibiotics (tetracycline). By adopting an ecological approach, we observed that blood infections are associated with the broadest range of species compared to infections affecting other areas and we obtained clear indications on the antibiotics that should be preferred in the treatment of infections at specific body sites. Future investigations carried out on a larger geographical scale will clarify whether these indications are limited to the geographical region investigated over this study, or whether the same trends are visible at national or international level.

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