Novel Biomimetic Human TLR2-Derived Peptides for Potential Targeting of Lipoteichoic Acid: An in Silico Assessment

Antimicrobial resistance is one of the most significant threats to health and economy around the globe and has been compounded by the emergence of COVID-19, raising important consequences for antimicrobial resistance development. Contrary to conventional targeting approaches, the use of biomimetic application via nanoparticles for enhanced cellular targeting, cell penetration and localized antibiotic delivery has been highlighted as a superior approach to identify novel targeting ligands for combatting antimicrobial resistance. Gram-positive bacterial cell walls contain lipoteichoic acid (LTA), which binds specifically to Toll-like receptor 2 (TLR2) on human macrophages. This phenomenon has the potential to be exploited for the design of biomimetic peptides for antibacterial application. In this study, we have derived peptides from sequences present in human TLR2 that bind to LTA with high affinity. In silico approaches including molecular modelling, molecular docking, molecular dynamics, and thermodynamics have enabled the identification of these crucial binding amino acids, the design of four novel biomimetic TLR2-derived peptides and their LTA binding potential. The outcomes of this study have revealed that one of these novel peptides binds to LTA more strongly and stably than the other three peptides and has the potential to enhance LTA targeting and bacterial cell penetration.

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Comparative analysis of antimicrobial resistance genes of Mycobacterium tuberculosis and Mycobacterium bovis in silico

International Journal of Infectious Diseases ◽

10.1016/j.ijid.2020.09.213 ◽

2020 ◽

Vol 101 ◽

pp. 70

Author(s):

T. Senbadejo ◽

T. Ganiyu ◽

L. Ezediuno ◽

C. Olaitan

Keyword(s):

Mycobacterium Tuberculosis ◽

Comparative Analysis ◽

Antimicrobial Resistance ◽

Mycobacterium Bovis ◽

Resistance Genes ◽

In Silico ◽

Antimicrobial Resistance Genes

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Multidrug Antimicrobial Resistance and Molecular Detection of mcr-1 Gene in Salmonella Species Isolated from Chicken

Animals ◽

10.3390/ani11010206 ◽

2021 ◽

Vol 11 (1) ◽

pp. 206

Author(s):

Md Bashir Uddin ◽

S.M. Bayejed Hossain ◽

Mahmudul Hasan ◽

Mohammad Nurul Alam ◽

Mita Debnath ◽

...

Keyword(s):

Functional Analysis ◽

Antimicrobial Resistance ◽

In Silico ◽

Salmonella Enterica ◽

Molecular Mechanisms ◽

Antimicrobial Agents ◽

Genetic Relationships ◽

Evolutionary Relationship ◽

Salmonella Spp ◽

Gram Negative

Colistin (polymyxin E) is widely used in animal and human medicine and is increasingly used as one of the last-resort antibiotics against Gram-negative bacilli. Due to the increased use of colistin in treating infections caused by multidrug-resistant Gram-negative bacteria, resistance to this antibiotic ought to be monitored. The study was undertaken to elucidate the molecular mechanisms, genetic relationships and phenotype correlations of colistin-resistant isolates. Here, we report the detection of the mcr-1 gene in chicken-associated Salmonella isolates in Bangladesh and its in-silico functional analysis. Out of 100 samples, 82 Salmonella spp. were isolated from chicken specimens (liver, intestine). Phenotypic disc diffusion and minimum inhibitory concentration (MIC) assay using different antimicrobial agents were performed. Salmonella isolates were characterized using PCR methods targeting genus-specific invA and mcr-1 genes with validation for the functional analysis. The majority of the tested Salmonella isolates were found resistant to colistin (92.68%), ciprofloxacin (73.17%), tigecycline (62.20%) and trimethoprim/sulfamethoxazole (60.98%). When screened using PCR, five out of ten Salmonella isolates were found to carry the mcr-1 gene. One isolate was confirmed for Salmonella enterica subsp. enterica serovar Enteritidis, and other four isolates were confirmed for Salmonella enterica subsp. enterica serovar Typhimurium. Sequencing and phylogenetic analysis revealed a divergent evolutionary relationship between the catalytic domain of Neisseria meningitidis lipooligosaccharide phosphoethanolamine transferase A (LptA) and MCR proteins, rendering them resistant to colistin. Three-dimensional homology structural analysis of MCR-1 proteins and molecular docking interactions suggested that MCR-1 and LptA share a similar substrate binding cavity, which could be validated for the functional analysis. The comprehensive molecular and in-silico analyses of the colistin resistance mcr-1 gene of Salmonella spp. of chicken origin in the present study highlight the importance of continued monitoring and surveillance for antimicrobial resistance among pathogens in food chain animals.

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Potential of nanoparticles encapsulated drugs for possible inhibition of the antimicrobial resistance development

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2021.111943 ◽

2021 ◽

Vol 141 ◽

pp. 111943

Author(s):

Ramendra Pati Pandey ◽

Riya Mukherjee ◽

Anjali Priyadarshini ◽

Archana Gupta ◽

Arpana Vibhuti ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Resistance Development

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Microbial Photoinactivation by Visible Light Results in Limited Loss of Membrane Integrity

Antibiotics ◽

10.3390/antibiotics10030341 ◽

2021 ◽

Vol 10 (3) ◽

pp. 341

Author(s):

Katharina Hoenes ◽

Richard Bauer ◽

Barbara Spellerberg ◽

Martin Hessling

Keyword(s):

Visible Light ◽

Pseudomonas Fluorescens ◽

Bacterial Cell ◽

Bacterial Species ◽

Membrane Integrity ◽

Cell Lysis ◽

Microbial Inactivation ◽

Bacterial Cells ◽

Resistance Development ◽

Transmission Electron

Interest in visible light irradiation as a microbial inactivation method has widely increased due to multiple possible applications. Resistance development is considered unlikely, because of the multi-target mechanism, based on the induction of reactive oxygen species by wavelength specific photosensitizers. However, the affected targets are still not completely identified. We investigated membrane integrity with the fluorescence staining kit LIVE/DEAD® BacLight™ on a Gram positive and a Gram negative bacterial species, irradiating Staphylococcus carnosus and Pseudomonas fluorescens with 405 nm and 450 nm. To exclude the generation of viable but nonculturable (VBNC) bacterial cells, we applied an ATP test, measuring the loss of vitality. Pronounced uptake of propidium iodide was only observed in Pseudomonas fluorescens at 405 nm. Transmission electron micrographs revealed no obvious differences between irradiated samples and controls, especially no indication of an increased bacterial cell lysis could be observed. Based on our results and previous literature, we suggest that visible light photoinactivation does not lead to rapid bacterial cell lysis or disruption. However, functional loss of membrane integrity due to depolarization or inactivation of membrane proteins may occur. Decomposition of the bacterial envelope following cell death might be responsible for observations of intracellular component leakage.

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Association between antimicrobial usage and resistance in Salmonella from poultry farms in Nigeria

BMC Veterinary Research ◽

10.1186/s12917-021-02938-2 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Abdurrahman Hassan Jibril ◽

Iruka N. Okeke ◽

Anders Dalsgaard ◽

John Elmerdahl Olsen

Keyword(s):

Treatment Outcome ◽

Antimicrobial Resistance ◽

Global Health ◽

Human Medicine ◽

Antimicrobial Use ◽

Resistance Development ◽

Use Patterns ◽

Antimicrobial Usage ◽

Poultry Farms ◽

Reduction Strategies

Abstract Background Antimicrobial resistance (AMR) is a global health threat affecting treatment outcome in animals and humans. A pre-requisite for development of AMR reduction strategies is knowledge of antimicrobial use patterns, and how these affect resistance development. The aim of this study was to determine antimicrobial usage (AMU) and whether such usage was associated with AMR in Salmonella from poultry farms in Northwest Nigeria. Results Fifteen (37%) of antimicrobial products observed contained compounds that are of highest priority and critically important for human medicine. Broilers chicken consumed higher (28 ± 14 mg/kg active ingredients) amounts of antimicrobials compared to layers (13 ± 8 mg/kg) per week (p = 0.0009). Surprisingly, chickens raised under backyard system consumed higher amounts of antimicrobials (34 ± 7 mg/kg) than poultry in other systems (p = 0.02). High levels of resistance to tetracycline (58%), sulphonamides (65%), ciprofloxacin (46%) and gentamicin (42%) correlated with high farm level usage of these antimicrobials, and there was a strong correlation (r = 0.9) between farm usage and resistance of isolates to the same antimicrobials (p = 0.03). Conclusion High AMU, including use of highest priority critically important antimicrobials was observed at poultry farms in Northwest Nigeria. AMU correlated with high levels of resistance. Communication of prudent use of antimicrobials to farmers and regulation to obtain reduction in AMU should be a priority.

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WGS based analysis of acquired antimicrobial resistance in human and non-human Acinetobacter baumannii isolates from a German perspective

BMC Microbiology ◽

10.1186/s12866-021-02270-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Gamal Wareth ◽

Christian Brandt ◽

Lisa D. Sprague ◽

Heinrich Neubauer ◽

Mathias W. Pletz

Keyword(s):

Antimicrobial Resistance ◽

Acinetobacter Baumannii ◽

Genome Sequencing ◽

Resistance Genes ◽

In Silico ◽

Acquired Resistance ◽

Whole Genome ◽

Chromosomal Gene ◽

Milk Samples ◽

Carbapenemase Gene

Abstract Background Acinetobacter baumannii ability to develop and acquire resistance makes it one of the most critical nosocomial pathogens globally. Whole-genome sequencing (WGS) was applied to identify the acquired or mutational variants of antimicrobial resistance (AMR) genes in 85 German A. baumannii strains utilizing Illumina technology. Additionally, the whole genome of 104 German isolates deposited in the NCBI database was investigated. Results In-silico analysis of WGS data revealed wide varieties of acquired AMR genes mediating resistance mostly to aminoglycosides, cephalosporins, carbapenems, sulfonamides, tetracyclines and macrolides. In the 189 analyzed genomes, the ant (3″)-IIa conferring resistance to aminoglycosides was the most frequent (55%), followed by blaADC.25 (38.6%) conferring resistance to cephalosporin, blaOXA-23 (29%) and the blaOXA-66 variant of the intrinsic blaOXA-51-likes (26.5%) conferring resistance to carbapenems, the sul2 (26%) conferring resistance to sulfonamides, the tet. B (19.5%) conferring resistance to tetracycline, and mph. E and msr. E (19%) conferring resistance to macrolides. blaTEM variants conferring resistance to cephalosporins were found in 12% of genomes. Thirteen variants of the intrinsic blaOXA-51 carbapenemase gene, blaOXA-510 and blaADC-25 genes were found in isolates obtained from dried milk samples. Conclusion The presence of strains harboring acquired AMR genes in dried milk raises safety concerns and highlights the need for changes in producing dried milk. Acquired resistance genes and chromosomal gene mutation are successful routes for disseminating AMR determinants among A. baumannii. Identification of chromosomal and plasmid-encoded AMR in the genome of A. baumannii may help understand the mechanism behind the genetic mobilization and spread of AMR genes.

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In silico identification of vaccine targets for 2019-nCoV

F1000Research ◽

10.12688/f1000research.22507.1 ◽

2020 ◽

Vol 9 ◽

pp. 145 ◽

Cited By ~ 7

Author(s):

Chloe Hyun-Jung Lee ◽

Hashem Koohy

Keyword(s):

T Cell ◽

In Silico ◽

Vaccine Development ◽

De Novo ◽

Cell Receptor ◽

Binding Potential ◽

Hla Alleles ◽

Immunogenic Peptides ◽

Novel Coronavirus ◽

Positional Weight

Background: The newly identified coronavirus known as 2019-nCoV has posed a serious global health threat. According to the latest report (18-February-2020), it has infected more than 72,000 people globally and led to deaths of more than 1,016 people in China. Methods: The 2019 novel coronavirus proteome was aligned to a curated database of viral immunogenic peptides. The immunogenicity of detected peptides and their binding potential to HLA alleles was predicted by immunogenicity predictive models and NetMHCpan 4.0. Results: We report in silico identification of a comprehensive list of immunogenic peptides that can be used as potential targets for 2019 novel coronavirus (2019-nCoV) vaccine development. First, we found 28 nCoV peptides identical to Severe acute respiratory syndrome-related coronavirus (SARS CoV) that have previously been characterized immunogenic by T cell assays. Second, we identified 48 nCoV peptides having a high degree of similarity with immunogenic peptides deposited in The Immune Epitope Database (IEDB). Lastly, we conducted a de novo search of 2019-nCoV 9-mer peptides that i) bind to common HLA alleles in Chinese and European population and ii) have T Cell Receptor (TCR) recognition potential by positional weight matrices and a recently developed immunogenicity algorithm, iPred, and identified in total 63 peptides with a high immunogenicity potential. Conclusions: Given the limited time and resources to develop vaccine and treatments for 2019-nCoV, our work provides a shortlist of candidates for experimental validation and thus can accelerate development pipeline.

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mSphere of Influence: Evolutionary Strategies To Sensitize Drug-Resistant Pathogens

mSphere ◽

10.1128/msphere.00313-19 ◽

2019 ◽

Vol 4 (3) ◽

Cited By ~ 1

Author(s):

Rebecca S. Shapiro

Keyword(s):

Drug Resistance ◽

Antimicrobial Resistance ◽

Genetic Interaction ◽

Interaction Networks ◽

Evolutionary Strategies ◽

Drug Resistant ◽

Bacterial Evolution ◽

Resistance Development ◽

Collateral Sensitivity ◽

Link Type

ABSTRACTRebecca S. Shapiro studies antimicrobial resistance and genetic interaction networks. In this mSphere of Influence article, she reflects on how the papers “Bacterial evolution of antibiotic hypersensitivity” by Lázár et al. (V. Lázár, G. Pal Singh, R. Spohn, I. Nagy, et al., Mol Syst Biol 9:700, 2013,https://doi.org/10.1038/msb.2013.57) and “Use of collateral sensitivity networks to design drug cycling protocols that avoid resistance development” by L. Imamovic and M. O. A. Sommer (Sci Transl Med 5:204ra132, 2013,https://doi.org/10.1126/scitranslmed.3006609) impacted her thinking about multigene interaction effects on drug resistance.

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