Abstract
Antimicrobial resistance (AMR) is a threat to global public health and the identification of genetic determinants of AMR is a critical component to epidemiological investigations. ...High-throughput sequencing (HTS) provides opportunities for investigation of AMR across all microbial genomes in a sample (i.e. the metagenome). Previously, we presented MEGARes, a hand-curated AMR database and annotation structure developed to facilitate the analysis of AMR within metagenomic samples (i.e. the resistome). Along with MEGARes, we released AmrPlusPlus, a bioinformatics pipeline that interfaces with MEGARes to identify and quantify AMR gene accessions contained within a metagenomic sequence dataset. Here, we present MEGARes 2.0 (https://megares.meglab.org), which incorporates previously published resistance sequences for antimicrobial drugs, while also expanding to include published sequences for metal and biocide resistance determinants. In MEGARes 2.0, the nodes of the acyclic hierarchical ontology include four antimicrobial compound types, 57 classes, 220 mechanisms of resistance, and 1,345 gene groups that classify the 7,868 accessions. In addition, we present an updated version of AmrPlusPlus (AMR ++ version 2.0), which improves accuracy of classifications, as well as expanding scalability and usability.
Antimicrobial resistance has become an imminent concern for public health. As methods for detection and characterization of antimicrobial resistance move from targeted culture and polymerase chain ...reaction to high throughput metagenomics, appropriate resources for the analysis of large-scale data are required. Currently, antimicrobial resistance databases are tailored to smaller-scale, functional profiling of genes using highly descriptive annotations. Such characteristics do not facilitate the analysis of large-scale, ecological sequence datasets such as those produced with the use of metagenomics for surveillance. In order to overcome these limitations, we present MEGARes (https://megares.meglab.org), a hand-curated antimicrobial resistance database and annotation structure that provides a foundation for the development of high throughput acyclical classifiers and hierarchical statistical analysis of big data. MEGARes can be browsed as a stand-alone resource through the website or can be easily integrated into sequence analysis pipelines through download. Also via the website, we provide documentation for AmrPlusPlus, a user-friendly Galaxy pipeline for the analysis of high throughput sequencing data that is pre-packaged for use with the MEGARes database.
Succinct colored de Bruijn graphs Muggli, Martin D; Bowe, Alexander; Noyes, Noelle R ...
Bioinformatics (Oxford, England),
10/2017, Letnik:
33, Številka:
20
Journal Article
Recenzirano
Odprti dostop
In 2012, Iqbal et al. introduced the colored de Bruijn graph, a variant of the classic de Bruijn graph, which is aimed at 'detecting and genotyping simple and complex genetic variants in an ...individual or population'. Because they are intended to be applied to massive population level data, it is essential that the graphs be represented efficiently. Unfortunately, current succinct de Bruijn graph representations are not directly applicable to the colored de Bruijn graph, which requires additional information to be succinctly encoded as well as support for non-standard traversal operations.
Our data structure dramatically reduces the amount of memory required to store and use the colored de Bruijn graph, with some penalty to runtime, allowing it to be applied in much larger and more ambitious sequence projects than was previously possible.
https://github.com/cosmo-team/cosmo/tree/VARI.
martin.muggli@colostate.edu.
Supplementary data are available at Bioinformatics online.
Bovine Respiratory Disease (BRD) represents a significant burden to the health of feedlot cattle and the profitability of the beef industry in the US.
Mannheimia haemolytica
is widely regarded as the ...primary bacterial pathogen driving acute BRD. While
Mycoplasma bovis
is most commonly implicated in chronic cases of BRD, this agent's potential role in acute stages of BRD is unclear. Therefore, this study aimed to evaluate potential associations between
M. bovis
and
M. haemolytica
during acute BRD in feedlot cattle. Nasal swabs (
n
= 1,044) were collected over time from feedlot cattle (
n
= 270) enrolled in an experiment assessing the effect of vaccination for Bovine Respiratory Syncytial Virus (BRSV). Swabs were analyzed for detection of
M. bovis, M. haemolytica, Pasteurella multocida, Histophilus somni
, and BRSV
via
multiplex qPCR assays. Data were analyzed using inverse conditional probability weighted (ICPW) logistic regression models to investigate potential effects of
M. bovis
presence on arrival (d0), day seven (d7) and day 14 (d14) post-arrival on
M. haemolytica
prevalence on day 28 (d28) post-arrival, adjusting for the previous history of
P. multocida, H. somni
, BRSV, BRD morbidity, and body weight. The potential association between time-to-BRD detection and
M. bovis
presence on d0, d7, and d14 post-arrival, was inferred
via
an ICPW time-to-event model. The presence of
M. bovis
in nasal swabs collected on d7 post-arrival was significantly associated with an increase in the prevalence of
M. haemolytica
on d28 (prevalence difference: 45%; 95% Confidence Interval: 31%, 60%;
P
-value < 0.001). Significant time-varying coefficients for
M. bovis
presence were detected at d0, d7, and d14 post-arrival in the ICPW time-to-event model (
P
-value < 0.001). The shortest median time-to-BRD detection was 29 days in cattle that were
M. bovis
positive on d0, d7, and d14 post-arrival and in those that were positive on d0 and d14 post-arrival. Under the conditions of this study, our findings suggest that
M. bovis
may be influencing the respiratory environment during the acute phase of BRD, increasing the abundance of
M. haemolytica
, which could have important impacts on the occurrence of BRD.
Methamphetamine use is a serious public health concern in many countries and is second to cannabis as the most widely abused illicit drug in the world. Effective management for methamphetamine ...dependence remains elusive and the large majority of methamphetamine users relapse following treatment. Areas covered: Progression in the understanding of the pharmacological basis of methamphetamine use has provided us with innovative opportunities to develop agents to treat dependence. The current review summarizes relevant literature on the neurobiological and clinical correlates associated with methamphetamine use. We then outline agents that have been explored for potential treatments in preclinical studies, human laboratory phase I and phase II trials over the last ten years. Expert opinion: No agent has demonstrated a broad and strong effect in achieving MA abstinence in Phase II trials. Agents with novel therapeutic targets appear promising. Advancement in MA treatment, including translation into practice, faces several clinical challenges.
Multidrug resistance (MDR) is a serious issue prevalent in various agriculture-related foodborne pathogens including Salmonella enterica (S. enterica) Typhimurium. Class I integrons have been ...detected in Salmonella spp. strains isolated from food producing animals and humans and likely play a critical role in transmitting antimicrobial resistance within and between livestock and human populations.
The main objective of our study was to characterize class I integron presence to identify possible integron diversity among and between antimicrobial resistant Salmonella Typhimurium isolates from various host species, including humans, cattle, swine, and poultry.
An association between integron presence with multidrug resistance was evaluated. One hundred and eighty-three S. Typhimurium isolates were tested for antimicrobial resistance (AMR). Class I integrons were detected and sequenced. Similarity of AMR patterns between host species was also studied within each integron type.
One hundred seventy-four (95.1%) of 183 S.Typhimurium isolates were resistant to at least one antimicrobial and 82 (44.8%) were resistant to 5 or more antimicrobials. The majority of isolates resistant to at least one antimicrobial was from humans (45.9%), followed by swine (19.1%) and then bovine (16.9%) isolates; poultry showed the lowest number (13.1%) of resistant isolates. Our study has demonstrated high occurrence of class I integrons in S. Typhimurium across different host species. Only one integron size was detected in poultry isolates. There was a significant association between integron presence of any size and specific multidrug resistance pattern among the isolates from human, bovine and swine.
Our study has demonstrated a high occurrence of class I integrons of different sizes in Salmonella Typhimurium across various host species and their association with multidrug resistance. This demonstration indicates that multidrug resistant Salmonella Typhimurium is of significant public health occurrence and reflects on the importance of judicious use of antimicrobials among livestock and poultry.
Background
Transmission of Salmonella in veterinary hospitals is typically associated with environmental contamination. Links between isolates recovered from hospitalized large animals and ...environment suggest animals as the likely source. Therefore, understanding factors influencing shedding is key in control. Shedding in hospitalized animals has been investigated, but many studies focused on subsets of animals limiting generalizability.
Objective
(1) Investigate factors associated with fecal shedding of Salmonella among hospitalized large animals at a veterinary hospital. (2) Compare results obtained using 2 comparison groups for risk factor analysis—large animals with high confidence in negative shedding status and those with potential for misclassification of shedding status.
Animals
Large animals admitted from March 2002 through December 2012.
Methods
A case‐control study was conducted among all hospitalized large animals that were routinely cultured as part of infection control efforts. Animal and hospital factors were evaluated. Data on factors of interest were collected retrospectively from electronic medical records. Multivariable conditional logistic regression was used to evaluate associations between animal factors and fecal shedding of Salmonella enterica.
Results
During the study period, 5.9% (648/11 061) of hospitalized large animals were culture positive for Salmonella, with the majority being cattle (72%; 467/648) and horses (22%; 143/648). Although the odds of shedding varied by comparison group, overall, 69.4% of animal shedding could be attributed to systemic illness (population attributable fraction) in this study.
Conclusions and Clinical Importance
Findings of this study inform our understanding of factors affecting Salmonella shedding in hospitalized large animals, thus improving our ability for implementation of evidence‐based control measures.
Previous research on stabilization methods for microbiome investigations has largely focused on human fecal samples. There are a few studies using feces from other species, but no published studies ...investigating preservation of samples collected from cattle. Given that microbial taxa are differentially impacted during storage it is warranted to study impacts of preservation methods on microbial communities found in samples outside of human fecal samples. Here we tested methods of preserving bovine fecal respiratory specimens for up to 2 weeks at four temperatures (room temperature, 4°C, -20°C, and -80°C) by comparing microbial diversity and community composition to samples extracted immediately after collection. Importantly, fecal specimens preserved and analyzed were technical replicates, providing a look at the effects of preservation method in the absence of biological variation. We found that preservation with the OMNIgene®•GUT kit resulted in community structure most like that of fresh samples extracted immediately, even when stored at room temperature (~20°C). Samples that were flash-frozen without added preservation solution were the next most representative of original communities, while samples preserved with ethanol were the least representative. These results contradict previous reports that ethanol is effective in preserving fecal communities and suggest for studies investigating cattle either flash-freezing of samples without preservative or preservation with OMNIgene®•GUT will yield more representative microbial communities.
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