David Engelthaler

David Engelthaler
Translational Genomics Research Institute | TGEN · TGen North

About

254
Publications
22,363
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Publications

Publications (254)
Preprint
Large scale outbreaks of the SARS-CoV-2 Delta variant have occurred in numerous settings, including universities. An outbreak of the SARS-CoV-2 Delta AY.25 lineage associated with a university campus with multiple transmission events was identified; genomic analyses characterized this outbreak and complemented contract tracing and wastewater survei...
Preprint
Whole-genome sequencing has advanced our understanding of the population structure of the pathogenic species complex Cryptococcus gattii, which has allowed for the phylogenomic specification of previously described major molecular type groupings and novel lineages. Recently, isolates collected in Mexico in the 1960s were determined to be geneticall...
Article
Full-text available
As is the case globally, Cryptococcus gattii is a less frequent cause of cryptococcosis than Cryptococcus neoformans in South Africa. We performed multilocus sequence typing (MLST) and fluconazole susceptibility testing of 146 isolates randomly selected from 750 South African patients with C . gattii disease identified through enhanced laboratory s...
Article
Full-text available
Background The incidence of multidrug-resistant tuberculosis (MDR-TB) remains critically high in countries of the former Soviet Union, where >20% of new cases and >50% of previously treated cases have resistance to rifampin and isoniazid. Transmission of resistant strains, as opposed to resistance selected through inadequate treatment of drug-susce...
Article
Genomic epidemiology has proven successful for real-time and retrospective monitoring of small and large-scale outbreaks. Here, we report two genomic sequencing and analysis strategies for rapid-turnaround or high-throughput processing of metagenomic samples. The rapid-turnaround method was designed to provide a quick phylogenetic snapshot of sampl...
Article
Full-text available
Background: Echinocandin resistance represents a great concern, as these drugs are recommended as first-line therapy for invasive candidiasis. Echinocandin resistance is conferred by mutations in FKS genes. Nevertheless, pathways are crucial for enabling tolerance, evolution, and maintenance of resistance. Therefore, understanding the biological p...
Article
Full-text available
Background: Pyrazinamide is an important component of both drug-susceptible and drug-resistant tuberculosis treatment regimens. Although approximately 50% of rifampicin resistant isolates are also resistant to pyrazinamide, pyrazinamide susceptibility testing is not routinely performed due to the challenging nature of the assay. We investigated the...
Article
Full-text available
The 2020 pandemic has transformed the world and elicited thousands of studies to better understand the SARS-CoV-2 virus. Viral load has been a common measure to monitor treatment therapies and associate viral dynamics with patient outcomes; however, methods associated with viral load have varied across studies. These variations have the potential t...
Article
Full-text available
Onchocerca lupi, Rodonaja 1967, is an emerging, zoonotic filarial nematode parasite that causes ocular disease in dogs, cats, wild canids, and humans. It is the causative agent of ocular onchocercosis in canines with increasing incidence in both North America and the Old World during the early twenty-first century. We report the complete mitochondr...
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Arizona's COVID-19 and Pets Program is a prospective surveillance study being conducted to characterize how SARS-CoV-2 impacts companion animals living in households with SARS-CoV-2-positive individuals. Among the enrolled pets, we identified a SARS-CoV-2-infected cat and dog from the same household; both animals were asymptomatic but had close con...
Preprint
Full-text available
The SARS-CoV-2 pandemic revealed the fragility of global supply chains, resulting in shortages of essential clinical supplies for the detection and treatment of COVID-19, including nasopharyngeal swabs (NP) commonly used to collect clinical samples for respiratory disease diagnostics. Groups around the world led a response to find alternatives to t...
Preprint
Full-text available
Background The incidence of multidrug-resistant tuberculosis (MDR-TB) remains critically high in countries of the former Soviet Union, where >20% of new cases and >50% of previously-treated cases have resistance to rifampin and isoniazid. Transmission of resistant strains, as opposed to resistance selected through inadequate treatment of drug-susce...
Article
Full-text available
Since the reemergence of St. Louis Encephalitis (SLE) Virus (SLEV) in the Southwest United States, identified during the 2015 outbreak in Arizona, SLEV has been seasonally detected within Culex spp. populations throughout the Southwest United States. Previous work revealed the 2015 outbreak was caused by an importation of SLEV genotype III, which h...
Article
Full-text available
Individuals living in congregate settings, including those in group homes, have been disproportionately impacted by COVID-19 and may be at increased risk of exposure or infection due to underlying illness. In mid-May 2020, local public health officials responded to an outbreak of COVID-19 among staff and residents associated with a multi-residentia...
Article
Full-text available
In South Africa, Cryptococcus neoformans is the most common cause of adult meningitis. We performed multi locus sequence typing and fluconazole susceptibility testing of clinical C. neoformans isolates collected from 251 South African patients with cryptococcosis through national surveillance from 2005 to 2009. We examined the association between c...
Article
Full-text available
Genomic epidemiology has proven successful for real-time and retrospective monitoring of small and large-scale outbreaks. Here, we report two genomic sequencing and analysis strategies for rapid-turnaround or high-throughput processing of metagenomic samples. The rapid-turnaround method was designed to provide a quick phylogenetic snapshot of sampl...
Article
Full-text available
Onchocerca lupi nematode infects dogs, cats, and humans, but whether it can be spread by coyotes has been unknown. We conducted surveillance for O. lupi nematode infection in coyotes in the southwestern United States. We identified multiple coyote populations in Arizona and New Mexico as probable reservoirs for this species.
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Full-text available
Odoribacter splanchnicus, belonging to the order Bacteroidales, is a common, short-chain fatty acid producing member of the human intestinal microbiota. A decreased abundance of Odoribacter has been linked to different microbiota-associated diseases, such as non-alcoholic fatty liver disease, cystic fibrosis and inflammatory bowel disease (IBD). Th...
Article
The COVID-19 pandemic has led to a rapid accumulation of SARS-CoV-2 genomes, enabling genomic epidemiology on local and global scales. Collections of genomes from resources such as GISAID must be subsampled to enable computationally feasible phylogenetic and other analyses. We present genome-sampler, a software package that supports sampling collec...
Article
Fluoroquinolones (FQ) are crucial components of multidrug-resistant tuberculosis (MDR TB) treatment. Varying levels of resistance are associated with specific mutations within the Quinolone Resistance Determining Region (QRDR) of gyrA . We sequenced the QRDR from serial isolates of MDR TB patients in the Preserving Effective TB Treatment Study (PET...
Article
Full-text available
As the COVID-19 pandemic swept across the United States, there was great differential impact on local and regional communities. One of the earliest and hardest hit regions was in New York, while at the same time Arizona (for example) had low incidence. That situation has changed dramatically, with Arizona now having the highest rate of disease incr...
Article
Full-text available
Antimicrobial resistance (AMR) in the nosocomial pathogen, Acinetobacter baumannii, is becoming a serious public health threat. While some mechanisms of AMR have been reported, understanding novel mechanisms of resistance is critical for identifying emerging resistance. One of the first steps in identifying novel AMR mechanisms is performing genoty...
Article
Pathogen genomic data are increasingly used to characterize global and local transmission patterns of important human pathogens and to inform public health interventions. Yet, there is no current consensus on how to measure genomic variation. To test the effect of the variant-identification approach on transmission inferences for Mycobacterium tube...
Article
Staphylococcus aureus is a colonizing opportunistic pathogen and a leading cause of bloodstream infection with high morbidity and mortality. S. aureus carriage frequency is reportedly between 20 and 40 % among healthy adults, with S. aureus colonization considered to be a risk factor for S. aureus bacteraemia. It is unknown whether a genetic compon...
Article
Full-text available
The COVID-19 pandemic has led to a rapid accumulation of SARS-CoV-2 genomes, enabling genomic epidemiology on local and global scales. Collections of genomes from resources such as GISAID must be subsampled to enable computationally feasible phylogenetic and other analyses. We present genome-sampler, a software package that supports sampling collec...
Preprint
Full-text available
St. Louis Encephalitis Virus (SLEV) has been seasonally detected within the Culex spp. populations within Maricopa County, Arizona and Coachella Valley, California since an outbreak in Maricopa County in 2015. Previous work revealed that the outbreak was caused by an importation of SLEV genotype III, which had only been detected within Argentina in...
Preprint
Full-text available
In December of 2019, a novel coronavirus, SARS-CoV-2, emerged in the city of Wuhan, China causing severe morbidity and mortality. Since then, the virus has swept across the globe causing millions of confirmed infections and hundreds of thousands of deaths. To better understand the nature of the pandemic and the introduction and spread of the virus...
Article
Full-text available
Rhizopus spp. fungi are ubiquitous in the environment and a rare but substantial cause of infection in immunosuppressed persons and surgery patients. During 2005-2017, an abnormally high number of Rhizopus infections in surgery patients, with no apparent epidemiologic links, were reported in Argentina. To determine the likelihood of a common source...
Article
Full-text available
Altered intestinal microbiota is associated with systemic and intestinal diseases, such as inflammatory bowel disease (IBD). Dysbiotic microbiota with enhanced proinflammatory capacity is characterized by depletion of anaerobic commensals, increased proportion of facultatively anaerobic bacteria, as well as reduced diversity and stability. In this...
Article
Full-text available
The full geographic range of coccidioidomycosis is unknown, although it is most likely expanding with environmental change. We report an apparently autochthonous coccidioidomycosis patient from Spokane, Washington, USA, a location to which Coccidioides spp. are not known to be endemic.
Preprint
Full-text available
Antimicrobial resistance (AMR) in the nosocomial pathogen, Acinetobacter baumannii, is becoming a serious public health threat. While some mechanisms of AMR have been reported, understanding novel mechanisms of resistance is critical for identifying emerging resistance. One of the first steps in identifying novel AMR mechanisms is performing genoty...
Article
Full-text available
The appearance of Cryptococcus gattii in the North American Pacific Northwest (PNW) in 1999 was an unexpected and is still an unexplained event. Recent phylogenomic analyses strongly suggest that this pathogenic fungus arrived in the PNW approximately 7 to 9 decades ago. In this paper, we theorize that the ancestors of the PNW C. gattii clones arri...
Article
Coccidioidomycosis is a debilitating fungal disease caused by inhalation of arthroconidia. We developed a novel approach for detection of airborne Coccidioides and used it to investigate the distribution of arthroconidia across the Phoenix, Arizona, metropolitan area. Air filters were collected daily from 21 stationary air-sampling units across the...
Article
There has been a considerable upsurge of extensive, treatment recalcitrant, dermatophytosis presenting as tinea corporis and tinea cruris in India since the past few years. Genome analysis of Trichophyton species causing severe superficial dermatophytosis in North India confirmed a unique clade most recently related to the T. mentagrophytes/interdi...
Preprint
Full-text available
Pathogen genomic data are increasingly used to characterize global and local transmission patterns of important human pathogens and to inform public health interventions. Yet there is no current consensus on how to measure genomic variation. We investigated the effects of variant identification approaches on transmission inferences for M. tuberculo...
Article
Multidrug-resistant tuberculosis is an alarming threat and targeted deep sequencing (DS) may be an effective method for rapid identification of drug-resistant profiles, including detection of heteroresistance. We evaluated sensitivity and specificity of targeted DS vs. phenotypic drug susceptibility testing (pDST) among patients starting first-line...
Article
Full-text available
Cryptococcus gattii molecular type VGII is one of the causes of cryptococcosis, a severe fungal disease that is acquired from the environment and affects many host species (including humans and koalas). In Australia, disease caused by C. gattii VGII is largely confined to western and central northern parts of the country, with sporadic cases report...
Article
We examined 5 tularemia cases in Arizona, USA, during 2015-2017. All were caused by Francisella tularensis group A.II. Genetically similar isolates were found across large spatial and temporal distances, suggesting that group A.II strains are dispersed across long distances by wind and exhibit low replication rates in the environment.
Article
Full-text available
Background Accurate, comprehensive, and timely detection of drug-resistant tuberculosis (TB) is essential to inform patient treatment and enable public health surveillance. This is crucial for effective control of TB globally. Whole-genome sequencing (WGS) and targeted next-generation sequencing (NGS) approaches have potential as rapid in vitro dia...
Data
Prospective analysis plan. (DOCX)
Data
Clarification of Illumina’s role and contribution to project. (PDF)
Data
WGS variant call percent agreement. WGS, whole-genome sequencing. (DOCX)
Article
Full-text available
Coccidioidomycosis is an emerging fungal infection in Washington, USA, and the epidemiology of the disease in this state is poorly understood. We used whole-genome sequencing to differentiate locally acquired cases in Washington on the basis of the previously identified phylogeographic population structure of Coccidioides spp. Clinical isolates fro...
Article
A child developed hydrocephalus. Sixteen months later, it was discovered to be a complication of coccidioidal meningitis. The infection's source was uncertain until genomic analysis of the fungal isolate identified its origin to be a visit to Beeville Texas. Improved national reporting of cases of coccidioidomycosis might reduce diagnostic delays.
Article
Full-text available
Enteroviruses frequently result in respiratory and gastrointestinal illness; however, multiple subtypes, including poliovirus, can cause severe neurologic disease. Recent biennial increases (i.e., 2014, 2016, and 2018) in cases of non-polio acute flaccid paralysis have led to speculations that other enteroviruses, specifically enterovirus D68 (EV-D...
Article
Full-text available
Increasingly, routine surveillance and monitoring of foodborne pathogens using whole-genome sequencing is creating opportunities to study foodborne illness epidemiology beyond routine outbreak investigations and case–control studies. Using a global phylogeny of Salmonella enterica serotype Typhimurium, we found that major livestock sources of the p...
Article
Full-text available
West Nile Virus (WNV) has been detected annually in Maricopa County, Arizona, since 2003. With this in mind, we sought to determine if contemporary strains are endemic to the county or are annually imported. As part of this effort, we developed a new protocol for tiled amplicon sequencing of WNV to efficiently attain greater than 99% coverage of 14...
Data
Sequence metadata in phylogenetic order. The Genbank accession number, the host or vector mosquito that the strain was isolated from, the state of isolation, isolation date to the nearest hundredths of a year, major WNV clade the strain belongs to, clade-defining amino acid substitutions, and notable convergent substitutions are included. We adopte...
Data
Tiled amplicon primer pairs. Primer pairs, the amplification pools to which they belong, primer lengths, melting temperature (Tm), GC content, and start and end position in relationship to the NY99 strain are included. This information was directly output from Primal Scheme [7]. (XLSX)
Data
Phylogenetically ordered amino acid alignment of the E protein. A valine at position 159 indicates the NY99 lineage, whereas an alanine indicates NA/WN02 or SW/WN03 lineages. (FAS)
Data
Phylogenetically ordered amino acid alignment of the NS4 protein. A threonine at position 85 indicates the SW/WN03 lineage. (FAS)
Data
Phylogenetically ordered amino acid alignment of the NS5 protein. A change from lysine to arginine at position 314 has occurred in several strains isolated in the southwestern United States, including all Arizona strains. (FAS)
Data
Model comparison results in duplicate from the generalized stepping stone sampling analyses. (XLSX)
Data
Phylogenetically ordered nucleotide alignment of the WNV coding region. (FAS)
Article
Full-text available
We conducted molecular clock analysis of whole-genome sequences from a set of autochthonous isolates of Cryptococcus gattii sensu stricto from the southeastern United States. Our analysis indicates that C. gattii arrived in the southeastern United States approximately 9,000-19,000 years ago, long before its arrival in the Pacific Northwest.
Article
Full-text available
Drug-resistant tuberculosis poses a persistent public health threat. The ReSeqTB platform is a collaborative, curated knowledgebase, designed to standardize and aggregate global Mycobacterium tuberculosis complex (MTBC) variant data from whole genome sequencing (WGS) with phenotypic drug susceptibility testing (DST) and clinical data. We developed...
Article
Background: Heteroresistant Mycobacterium tuberculosis (Mtb) infections (concomitant infection with drug-resistant and drug-susceptible Mtb) may explain the higher risk of poor tuberculosis (TB) treatment outcomes observed among patients with mixed-strain Mtb infections. We investigated the clinical effect of mixed infections while controlling for...
Article
Strains of Staphylococcus aureus in clonal complex 8 (CC8), including USA300, USA500, and the Iberian clone, are prevalent pathogens in the United States, both inside and outside health care settings. Methods for typing CC8 strains are becoming obsolete as the strains evolve and diversify, and whole-genome sequencing has shown that some strain type...