scholarly journals ProphET, Prophage Estimation Tool: a standalone prophage sequence prediction tool with self-updating reference database

2017 ◽  
Author(s):  
João L. Reis-Cunha ◽  
Daniella C. Bartholomeu ◽  
Ashlee M. Earl ◽  
Bruce W. Birren ◽  
Gustavo C. Cerqueira
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Bacterial Genome ◽  
Initial Step ◽  
Reference Database ◽  
Public Health Decision ◽  
Resistance Factors ◽  
Health Decision ◽  
Integration Sites ◽  
Prophage Sequence

AbstractProphages are a significant force in prokaryote evolution. The remaining sequences of a bacteriophage integration event are known for altering gene expression, enabling creative destruction of the bacterial genome and to induce pathogenicity by harboring and transposing virulence and antibiotic resistance factors. In the light of the dreadful expansion of antibiotic resistance bacteriophages have gathered renewed interest from the scientific community and public health decision makers as a promising long forgotten alternative to control bacterial infections. Cataloging the repertoire of prophages and their integration sites is an important initial step in the understanding of bacteriophages either as tool or as a threat. In this work, we present ProphET (Prophage Estimation Tool), a standalone application without the limitations of their web based counterparts and which identifies prophages in bacterial genomes with higher precision than similar applications.

scholarly journals The rising impact of mathematical modelling in epidemiology: antibiotic resistance research as a case study

2007 ◽  
Vol 136 (3) ◽  
pp. 289-298 ◽  
Author(s):  
L. TEMIME ◽  
G. HEJBLUM ◽  
M. SETBON ◽  
A. J. VALLERON
Keyword(s):  
Public Health ◽  
Antibiotic Resistance ◽  
Mathematical Modelling ◽  
Citation Impact ◽  
Temporal Trends ◽  
Public Health Decision ◽  
Health Decision Making ◽  
Health Decision ◽  
Scientific Fields

SUMMARYMathematical modelling of infectious diseases has gradually become part of public health decision-making in recent years. However, the developing status of modelling in epidemiology and its relationship with other relevant scientific approaches have never been assessed quantitatively. Herein, using antibiotic resistance as a case study, 60 published models were analysed. Their interactions with other scientific fields are reported and their citation impact evaluated, as well as temporal trends. The yearly number of antibiotic resistance modelling publications increased significantly between 1990 and 2006. This rise cannot be explained by the surge of interest in resistance phenomena alone. Moreover, modelling articles are, on average, among the most frequently cited third of articles from the journal in which they were published. The results of this analysis, which might be applicable to other emerging public health problems, demonstrate the growing interest in mathematical modelling approaches to evaluate antibiotic resistance.

scholarly journals Associations among Antibiotic and Phage Resistance Phenotypes in Natural and Clinical Escherichia coli Isolates

mBio ◽  
2017 ◽  
Vol 8 (5) ◽  
Author(s):  
Richard C. Allen ◽  
Katia R. Pfrunder-Cardozo ◽  
Dominik Meinel ◽  
Adrian Egli ◽  
Alex R. Hall
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Antibacterial Agents ◽  
Core Genome ◽  
Bacterial Genome ◽  
Abundant Species ◽  
Phage Resistance ◽  
Resistance Evolution ◽  
Genome Phylogeny

ABSTRACT The spread of antibiotic resistance is driving interest in new approaches to control bacterial pathogens. This includes applying multiple antibiotics strategically, using bacteriophages against antibiotic-resistant bacteria, and combining both types of antibacterial agents. All these approaches rely on or are impacted by associations among resistance phenotypes (where bacteria resistant to one antibacterial agent are also relatively susceptible or resistant to others). Experiments with laboratory strains have shown strong associations between some resistance phenotypes, but we lack a quantitative understanding of associations among antibiotic and phage resistance phenotypes in natural and clinical populations. To address this, we measured resistance to various antibiotics and bacteriophages for 94 natural and clinical Escherichia coli isolates. We found several positive associations between resistance phenotypes across isolates. Associations were on average stronger for antibacterial agents of the same type (antibiotic-antibiotic or phage-phage) than different types (antibiotic-phage). Plasmid profiles and genetic knockouts suggested that such associations can result from both colocalization of resistance genes and pleiotropic effects of individual resistance mechanisms, including one case of antibiotic-phage cross-resistance. Antibiotic resistance was predicted by core genome phylogeny and plasmid profile, but phage resistance was predicted only by core genome phylogeny. Finally, we used observed associations to predict genes involved in a previously uncharacterized phage resistance mechanism, which we verified using experimental evolution. Our data suggest that susceptibility to phages and antibiotics are evolving largely independently, and unlike in experiments with lab strains, negative associations between antibiotic resistance phenotypes in nature are rare. This is relevant for treatment scenarios where bacteria encounter multiple antibacterial agents. IMPORTANCE Rising antibiotic resistance is making it harder to treat bacterial infections. Whether resistance to a given antibiotic spreads or declines is influenced by whether it is associated with altered susceptibility to other antibiotics or other stressors that bacteria encounter in nature, such as bacteriophages (viruses that infect bacteria). We used natural and clinical isolates of Escherichia coli, an abundant species and key pathogen, to characterize associations among resistance phenotypes to various antibiotics and bacteriophages. We found associations between some resistance phenotypes, and in contrast to past work with laboratory strains, they were exclusively positive. Analysis of bacterial genome sequences and horizontally transferred genetic elements (plasmids) helped to explain this, as well as our finding that there was no overall association between antibiotic resistance and bacteriophage resistance profiles across isolates. This improves our understanding of resistance evolution in nature, potentially informing new rational therapies that combine different antibacterials, including bacteriophages. IMPORTANCE Rising antibiotic resistance is making it harder to treat bacterial infections. Whether resistance to a given antibiotic spreads or declines is influenced by whether it is associated with altered susceptibility to other antibiotics or other stressors that bacteria encounter in nature, such as bacteriophages (viruses that infect bacteria). We used natural and clinical isolates of Escherichia coli, an abundant species and key pathogen, to characterize associations among resistance phenotypes to various antibiotics and bacteriophages. We found associations between some resistance phenotypes, and in contrast to past work with laboratory strains, they were exclusively positive. Analysis of bacterial genome sequences and horizontally transferred genetic elements (plasmids) helped to explain this, as well as our finding that there was no overall association between antibiotic resistance and bacteriophage resistance profiles across isolates. This improves our understanding of resistance evolution in nature, potentially informing new rational therapies that combine different antibacterials, including bacteriophages.

Persons with Disabilities and Public Health Ethics

2019 ◽  
pp. 218-231
Author(s):  
Monika Mitra ◽  
Linda Long-Bellil ◽  
Robyn Powell
Keyword(s):  
Public Health ◽  
Health Policy ◽  
Public Health Policy ◽  
Ethical Issues ◽  
The United States ◽  
Policy And Practice ◽  
Persons With Disabilities ◽  
Public Health Decision ◽  
Health Decision ◽  
Health Policy And Practice

This chapter draws on medical, social, and legal perspectives to identify and highlight ethical issues pertaining to the treatment, representation, and inclusion of persons with disabilities in public health policy and practice. A brief history of disability in the United States is provided as a context for examining the key ethical issues related to public health policy and practice. Conceptual frameworks and approaches to disability are then described and applied. The chapter then discusses the imperativeness of expanding access to public health programs by persons with disabilities, the need to address implicit and structural biases, and the importance of including persons with disabilities in public health decision-making.

scholarly journals Novel Soil-Derived Beta-Lactam, Chloramphenicol, Fosfomycin and Trimethoprim Resistance Genes Revealed by Functional Metagenomics

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 378
Author(s):  
Inka Marie Willms ◽  
Maja Grote ◽  
Melissa Kocatürk ◽  
Lukas Singhoff ◽  
Alina Andrea Kraft ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Reference Database ◽  
Functional Metagenomics ◽  
Beta Lactam ◽  
Public Attention ◽  
Soil Ecosystems ◽  
High Level ◽  
Antibiotic Efflux

Antibiotic resistance genes (ARGs) in soil are considered to represent one of the largest environmental resistomes on our planet. As these genes can potentially be disseminated among microorganisms via horizontal gene transfer (HGT) and in some cases are acquired by clinical pathogens, knowledge about their diversity, mobility and encoded resistance spectra gained increasing public attention. This knowledge offers opportunities with respect to improved risk prediction and development of strategies to tackle antibiotic resistance, and might help to direct the design of novel antibiotics, before further resistances reach hospital settings or the animal sector. Here, metagenomic libraries, which comprise genes of cultivated microorganisms, but, importantly, also those carried by the uncultured microbial majority, were screened for novel ARGs from forest and grassland soils. We detected three new beta-lactam, a so far unknown chloramphenicol, a novel fosfomycin, as well as three previously undiscovered trimethoprim resistance genes. These ARGs were derived from phylogenetically diverse soil bacteria and predicted to encode antibiotic inactivation, antibiotic efflux, or alternative variants of target enzymes. Moreover, deduced gene products show a minimum identity of ~21% to reference database entries and confer high-level resistance. This highlights the vast potential of functional metagenomics for the discovery of novel ARGs from soil ecosystems.

scholarly journals Phage-Encoded Endolysins

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 124
Author(s):  
Fatma Abdelrahman ◽  
Maheswaran Easwaran ◽  
Oluwasegun I. Daramola ◽  
Samar Ragab ◽  
Stephanie Lynch ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cell Wall ◽  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Therapeutic Strategies ◽  
Therapeutic Application ◽  
Significant Evidence ◽  
Crucial Information

Due to the global emergence of antibiotic resistance, there has been an increase in research surrounding endolysins as an alternative therapeutic. Endolysins are phage-encoded enzymes, utilized by mature phage virions to hydrolyze the cell wall from within. There is significant evidence that proves the ability of endolysins to degrade the peptidoglycan externally without the assistance of phage. Thus, their incorporation in therapeutic strategies has opened new options for therapeutic application against bacterial infections in the human and veterinary sectors, as well as within the agricultural and biotechnology sectors. While endolysins show promising results within the laboratory, it is important to document their resistance, safety, and immunogenicity for in-vivo application. This review aims to provide new insights into the synergy between endolysins and antibiotics, as well as the formulation of endolysins. Thus, it provides crucial information for clinical trials involving endolysins.

scholarly journals Silencing Antibiotic Resistance with Antisense Oligonucleotides

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 416
Author(s):  
Saumya Jani ◽  
Maria Soledad Ramirez ◽  
Marcelo E. Tolmasky
Keyword(s):  
Antibiotic Resistance ◽  
Nucleic Acids ◽  
Antisense Oligonucleotides ◽  
Bacterial Infections ◽  
Genetic Disorders ◽  
Antibiotic Resistance Genes ◽  
Short Review ◽  
Rnase H ◽  
Biological Processes ◽  
Locked Nucleic Acids

Antisense technologies consist of the utilization of oligonucleotides or oligonucleotide analogs to interfere with undesirable biological processes, commonly through inhibition of expression of selected genes. This field holds a lot of promise for the treatment of a very diverse group of diseases including viral and bacterial infections, genetic disorders, and cancer. To date, drugs approved for utilization in clinics or in clinical trials target diseases other than bacterial infections. Although several groups and companies are working on different strategies, the application of antisense technologies to prokaryotes still lags with respect to those that target other human diseases. In those cases where the focus is on bacterial pathogens, a subset of the research is dedicated to produce antisense compounds that silence or reduce expression of antibiotic resistance genes. Therefore, these compounds will be adjuvants administered with the antibiotic to which they reduce resistance levels. A varied group of oligonucleotide analogs like phosphorothioate or phosphorodiamidate morpholino residues, as well as peptide nucleic acids, locked nucleic acids and bridge nucleic acids, the latter two in gapmer configuration, have been utilized to reduce resistance levels. The major mechanisms of inhibition include eliciting cleavage of the target mRNA by the host’s RNase H or RNase P, and steric hindrance. The different approaches targeting resistance to β-lactams include carbapenems, aminoglycosides, chloramphenicol, macrolides, and fluoroquinolones. The purpose of this short review is to summarize the attempts to develop antisense compounds that inhibit expression of resistance to antibiotics.

scholarly journals The NCCMT’s dynamic model for evidence-informed public health

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
E Clark ◽  
S Neil-Sztramko ◽  
M Dobbins
Keyword(s):  
Public Health ◽  
Decision Making ◽  
Research Evidence ◽  
Decision Makers ◽  
Local Data ◽  
Public Health Decision ◽  
Health Decision Making ◽  
Political Preferences ◽  
Health Decision ◽  
Structured Approach

Abstract Issue It is well accepted that public health decision makers should use the best available research evidence in their decision-making process. However, research evidence alone is insufficient to inform public health decision making. Description of the problem As new challenges to public health emerge, there can be a paucity of high quality research evidence to inform decisions on new topics. Public health decision makers must combine various sources of evidence with their public health expertise to make evidence-informed decisions. The National Collaborating Centre for Methods and Tools (NCCMT) has developed a model which combines research evidence with other critical sources of evidence that can help guide decision makers in evidence-informed decision making. Results The NCCMT's model for evidence-informed public health combines findings from research evidence with local data and context, community and political preferences and actions and evidence on available resources. The model has been widely used across Canada and worldwide, and has been integrated into many public health organizations' decision-making processes. The model is also used for teaching an evidence-informed public health approach in Masters of Public Health programs around the globe. The model provides a structured approach to integrating evidence from several critical sources into public health decision making. Use of the model helps ensure that important research, contextual and preference information is sought and incorporated. Lessons Next steps for the model include development of a tool to facilitate synthesis of evidence across all four domains. Although Indigenous knowledges are relevant for public health decision making and should be considered as part of a complete assessment the current model does not capture Indigenous knowledges. Key messages Decision making in public health requires integrating the best available evidence, including research findings, local data and context, community and political preferences and available resources. The NCCMT’s model for evidence-informed public health provides a structured approach to integrating evidence from several critical sources into public health decision making.

scholarly journals Characterization of Two Multidrug-Resistant IncA/C Plasmids from the 1960s by Using the MinION Sequencer Device

2016 ◽  
Vol 60 (11) ◽  
pp. 6780-6786 ◽  
Author(s):  
Mónika Szabó ◽  
Tibor Nagy ◽  
Tímea Wilk ◽  
Tibor Farkas ◽  
Anna Hegyi ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Genome ◽  
Multidrug Resistant ◽  
Phenotypic Change ◽  
Long Reads ◽  
Loss Of Resistance ◽  
Rapid Characterization ◽  
Resistance Island ◽  
The 1960S

ABSTRACTTwo A/C incompatibility group (IncA/C family) plasmids from the 1960s have been sequenced and classified into the A/C2type 1 group. R16a and IP40a contain novel antibiotic resistance islands and a complete GIsul2 genomic island not previously found in the family. In the 173.1-kb R16a, the 29.9-kb antibiotic resistance island (ARI) is located in a unique backbone position not utilized by ARIs. ARIR16aconsists of Tn1, Tn6020, and Tn6333, harboring the resistance genesblaTEM-1DandaphA1band amermodule, respectively; a truncated Tn5393copy; and a gene cluster with unknown function. Plasmid IP40a is 170.4 kb in size and contains a 5.6-kb ARI inserted into thekfrAgene. ARIIP40acarryingblaTEM-1DandaphA1bgenes is composed of Tn1with a Tn6023insertion. Additionally, IP40a harbors single IS2, IS186, and Tn1000insertions scattered in the backbone; an IS150copy in GIsul2; and a complete Tn6333carrying amermodule at the position of ARIR16a. Loss of resistance markers in R16a, IP40a, and R55 was observed during stability tests. Every phenotypic change proved to be the result of recombination events involving mobile elements. Intramolecular transposition of IS copies that generated IP40a derivatives lacking large parts of the backbone could account for the formation of other family members, too. The MinION platform proved to be a valuable tool in bacterial genome sequencing since it generates long reads that span repetitive elements and facilitates full-length plasmid or chromosome assembly. Nanopore technology enables rapid characterization of large, low-copy-number plasmids and their rearrangement products.

Sign in / Sign up

Export Citation Format

Share Document