- Reproductive tract infections research
- Antibiotic Resistance in Bacteria
- Bacterial Identification and Susceptibility Testing
- COVID-19 epidemiological studies
- Bacterial Infections and Vaccines
- Animal Virus Infections Studies
- SARS-CoV-2 and COVID-19 Research
- Syphilis Diagnosis and Treatment
- Viral gastroenteritis research and epidemiology
- Antibiotics Pharmacokinetics and Efficacy
- Food Allergy and Anaphylaxis Research
- SARS-CoV-2 detection and testing
- Antibiotic Use and Resistance
- Food Safety and Hygiene
- Zoonotic diseases and public health
- Pharmaceutical Practices and Patient Outcomes
- Amoebic Infections and Treatments
- Urticaria and Related Conditions
- Contact Dermatitis and Allergies
- Hepatitis B Virus Studies
- Tuberculosis Research and Epidemiology
- Diabetes Management and Education
- Bat Biology and Ecology Studies
- Hepatitis Viruses Studies and Epidemiology
- Drug-Induced Adverse Reactions
Children's Hospital Colorado
2023
University of Colorado Denver
2023
University of California, Berkeley
2023
Ginkgo BioWorks (United States)
2022
Greater Baltimore Medical Center
2022
Harvard University
2019-2020
Boston University
2020
Columbia University
2014-2017
Rutgers, The State University of New Jersey
2011-2014
Since the emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Syndrom (MERS-CoV) it has become increasingly clear that bats are important reservoirs CoVs. Despite this, only 6% all CoV sequences in GenBank from bats. The remaining 94% largely consist known pathogens public health or agricultural significance, indicating current research effort is heavily biased towards describing diseases rather than 'pre-emergent' diversity Our study addresses this critical...
The evolutionary origins of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) are unknown. Current evidence suggests that insectivorous bats likely to be the original source, as several 2c CoVs have been described from various species in family Vespertilionidae Here, we describe a MERS-like CoV identified Pipistrellus cf. hesperidus bat sampled Uganda (strain PREDICT/PDF-2180), further supporting hypothesis source MERS-CoV. Phylogenetic analysis showed PREDICT/PDF-2180 is...
Abstract It is currently unclear whether changes in viral communities will ever be predictable. Here we investigate wildlife are inherently structured (inferring predictability) by looking at assembled through deterministic (often predictable) or stochastic (not processes. We sample macaque faeces across nine sites Bangladesh and use consensus PCR sequencing to discover 184 viruses from 14 families. then network modelling statistical null-hypothesis testing show the presence of non-random...
Abstract Neisseria gonorrhoeae is an urgent public health threat due to rapidly increasing incidence and antibiotic resistance. In contrast with the trend of resistance, clinical isolates that have reverted susceptibility regularly appear, prompting questions about which pressures compete antibiotics shape gonococcal evolution. Here, we used genome-wide association identify loss-of-function (LOF) mutations in efflux pump mtrCDE operon as a mechanism increased demonstrate these are...
Abstract The emergence of resistance to azithromycin complicates treatment Neisseria gonorrhoeae , the etiologic agent gonorrhea. Substantial remains unexplained after accounting for known mutations. Bacterial genome-wide association studies (GWAS) can identify novel genes but must control genetic confounders while maintaining power. Here, we show that compared single-locus GWAS, conducting GWAS conditioned on mutations reduces number false positives and identifies a G70D mutation in RplD...
Describing the viral diversity of wildlife can provide interesting and useful insights into natural history established human pathogens. In this study, we describe a previously unknown picornavirus in harbor seals (tentatively named phopivirus) that is related to hepatitis A virus (HAV). We show phopivirus shares several genetic phenotypic characteristics with HAV, including phylogenetic relatedness across genome, specific seemingly quiescent tropism for hepatocytes, structural conservation...
Abstract We enrolled arriving international air travelers in a severe acute respiratory syndrome coronavirus 2 genomic surveillance program. used molecular testing of pooled nasal swabs and sequenced positive samples for sublineage. Traveler-based provided early-warning variant detection, reporting the first US Omicron BA.2 BA.3 North America.
Respiratory infections are important causes of morbidity and mortality in reptiles; however, the causative agents only infrequently identified. Pneumonia, tracheitis esophagitis were reported a collection ball pythons (Python regius). Eight 12 snakes had evidence bacterial pneumonia. High-throughput sequencing total extracted nucleic acids from lung, esophagus spleen revealed novel nidovirus. PCR indicated presence viral RNA trachea, esophagus, liver, spleen. In situ hybridization confirmed...
The high rates of RNA virus evolution are generally attributed to replication with error-prone RNA-dependent polymerases. However, these long-term nucleotide substitution span three orders magnitude and do not correlate well mutation or selection pressures. This rate variation may be explained by differences in ecology intrinsic genomic properties. We generated estimates for mammalian viruses compiled comparable published rates, yielding a dataset 118 structural genes from 51 different...
Picornaviruses have some of the highest nucleotide substitution rates among viruses, but there been no comparisons evolutionary within this broad family. We combined our own Bayesian coalescent analyses VP1 regions from four picornaviruses with 22 published to produce first within-family meta-analysis viral rates. Similarly, we compared rate estimates for RNA polymerase 3D(pol) gene five viruses Both a structural and nonstructural show that enteroviruses are evolving, on average, half order...
The sensitivity of genotype-based diagnostics that predict antimicrobial susceptibility is limited by the extent to which they detect genes and alleles lead resistance. As novel resistance variants are expected emerge, such decline unless new detected incorporated into diagnostic. Here, we present a mathematical framework define how many diagnostic failures may be under varying surveillance regimes thus quantify needed maintain diagnostics.
The literature is ripe with phylogenetic estimates of nucleotide substitution rates, especially measurably evolving species such as RNA viruses. However, it not known how robust these rate are to inaccuracies in the data, particularly sampling dates that used for molecular clock calibration. Here we report on evolution emerging pathogen Rabbit hemorrhagic disease virus (RHDV), which has significantly different rates same outer capsid (VP60) gene published literature. In an attempt reconcile...
Genotype-based diagnostics for antibiotic resistance represent a promising alternative to empiric therapy, reducing inappropriate use. However, because such assays infer based on known genetic markers, their utility will wane with the emergence of novel resistance. Maintenance these therefore require surveillance ensure early detection variants, but efficient strategies do so remain undefined. We evaluate efficiency targeted sampling approaches informed by patient and pathogen...
Abstract Neisseria gonorrhoeae is an urgent public health threat due to rapidly increasing incidence and antibiotic resistance. In contrast with the trend of resistance, clinical isolates that have reverted susceptibility regularly appear, prompting questions about which pressures compete antibiotics shape gonococcal evolution. Here, we used genome-wide association on largest collection N. date (n=4852) identify loss-of-function (LOF) mutations in efflux pump mtrCDE operon as a mechanism...
Abstract Prediction of antibiotic resistance phenotypes from whole genome sequencing data by machine learning methods has been proposed as a promising platform for the development sequence-based diagnostics. However, there no systematic evaluation factors that may influence performance such models, how they might apply to and vary across clinical populations, what implications be in setting. Here, we performed meta-analysis seven large Neisseria gonorrhoeae datasets, well Klebsiella...
Abstract The emergence of resistance to azithromycin complicates treatment N. gonorrhoeae , the etiologic agent gonorrhea. Population genomic analyses clinical isolates have demonstrated that some remains unexplained after accounting for contributions known mutations in 23S rRNA and MtrCDE efflux pump. Bacterial genome-wide association studies (GWAS) offer a promising approach identifying novel genes but must adequately address challenge controlling genetic confounders while maintaining...
Mycobacterium abscessus (Mab) is a clinically significant pathogen and highly genetically diverse species due to its large accessory genome. The functional consequence of this diversity remains unknown mainly because, date, genomic studies in Mab have been primarily performed on reference strains. Given the growing public health threat infections, understanding differences among clinical isolates can provide more insight into how genetic influences gene essentiality, relevant phenotypes,...
We enrolled arriving international air travelers in SARS-CoV-2 genomic surveillance, using molecular testing of pooled nasal swabs, and sequencing positive samples for viral lineage. Traveler-based surveillance provided early warning variant detection; we reported the first U.S. Omicron BA.2 BA.3 North America, weeks before next detection.
Abstract Diagnostics that minimize the time to selection of an appropriate antibiotic treatment represent important strategy in addressing challenge antimicrobial resistance (AMR). Among this class diagnostics, use pathogen genotype predict AMR phenotype has been facilitated by advances rapid sequencing platforms. A longstanding objection approach, however, is emergence novel mechanisms will inevitably lead a decline sensitivity these diagnostics. Here, we show while sensitivities some...
Abstract Genotype-based diagnostics for antibiotic resistance represent a promising alternative to empiric therapy, reducing inappropriate and ineffective use. However, because such assays infer phenotypes based on the presence or absence of known genetic markers, their utility will wane in response emergence novel resistance. Maintenance these therefore require surveillance designed ensure early detection variants, but efficient strategies do so remain be defined. Here, we evaluate...
ABSTRACT Objectives Mathematical modelling and genomic analyses are powerful methods for investigating the transmission dynamics of Neisseria gonorrhoeae , however, often make implicit assumption that N. isolates at different anatomical sites within same individual strain. Methods In this study, two approaches were used to explore genetic diversity. First, we examined a collection stored, clinical sourced from multiple single individuals attending sexual health clinic in Melbourne 2011-2019....
Abstract Background International travel facilitates SARS-CoV-2 spread globally. Early detection of variants among arriving international travelers could provide viral information about introduction with differing infectivity, virulence, and vaccine effectiveness, enabling adjustments to treatment prevention strategies. We initiated a genomic surveillance program at 4 US airports detect travelers. Methods Between November 29, 2021-April 24, 2022, we enrolled air (≥18 years) from flights...