Biology subjects

David M Engelthaler

Publications and source records attributed to David M Engelthaler.

3 recordsLinked to original sources

bioRxiv2016

Whole genome SNP typing to investigate methicillin-resistant Staphylococcus aureus carriage in a health-care provider as the source of multiple surgical site infections.

BackgroundPrevention of nosocomial transmission of infections is a central responsibility in the healthcare environment, and accurate identification of transmission events presents the first challenge. Phylogenetic analysis based on whole genome sequencing provides a high-resolution approach for accurately relating isolates to one another, allowing precise identification or exclusion of transmission events and sources for nearly all cases. We sequenced 24 methicillin-resistant Staphylococcus aureus (MRSA) genomes to retrospectively investigate a suspected point source of three surgical site infections (SSIs) that occurred over a one-year period. The source of transmission was believed to be a surgical team member colonized with MRSA, involved in all surgeries preceding the SSI cases, who was subsequently decolonized. Genetic relatedness among isolates was determined using whole genome single nucleotide polymorphism (SNP) data.\n\nResultsWhole genome SNP typing (WGST) revealed 283 informative SNPs between the surgical team members isolate and the closest SSI isolate. The second isolate was 286 and the third was thousands of SNPs different, indicating the nasal carriage strain from the surgical team member was not the source of the SSIs. Given the mutation rates estimated for S. aureus, none of the SSI isolates share a common ancestor within the past 14 years, further discounting any common point source for these infections. The decolonization procedures and resources spent on the point source infection control could have been prevented if WGST was performed at the time of the suspected transmission, instead of retrospectively.\n\nConclusionsWhole genome sequence analysis is an ideal method to exclude isolates involved in transmission events and nosocomial outbreaks, and coupling this method with epidemiological data can determine if a transmission event occurred. These methods promise to direct infection control resources more appropriately.

Genomics↗

bioRxiv2016

KlebSeq: A Diagnostic Tool for Healthcare Surveillance and Antimicrobial Resistance Monitoring of Klebsiella pneumoniae

Healthcare-acquired infections (HAIs) kill tens of thousands of people each year and add significantly to healthcare costs. Multidrug resistant and epidemic strains are a large proportion of HAI agents, and multidrug resistant strains of Klebsiella pneumoniae, a leading HAI agent, have become an urgent public health crisis. In the healthcare environment, patient colonization of K. pneumoniae precedes infection, and transmission via colonization leads to outbreaks. Periodic patient screening for K. pneumoniae colonization has cost-effective and life-saving potential. In this study, we describe the design and validation of KlebSeq, a highly informative screening tool that detects Klebsiella species and identifies clinically important strains and characteristics using highly multiplexed amplicon sequencing without a live culturing step. We demonstrate the utility of this tool on several complex specimen types including urine, wound swabs and tissue, several types of respiratory, and fecal, showing K. pneumoniae species and clonal group identification and antimicrobial resistance and virulence profiling, including capsule typing. Use of this amplicon sequencing tool can be used to screen patients for K. pneumoniae carriage to assess risk of infection and outbreak potential, and the expansion of this tool can be used for several other HAI agents or applications.

Molecular Biology↗

bioRxiv2015

Local population structure and patterns of Western Hemisphere dispersal for Coccidioides spp., the fungal cause of Valley Fever

Coccidioidomycosis (or Valley Fever) is a fungal disease with high morbidity and mortality that affects tens of thousands of people each year. This infection is caused by two sibling species, Coccidioides immitis and C. posadasii, which are endemic to specific arid locales throughout the Western Hemisphere, particularly the desert southwest of the United States. Recent epidemiological and population genetic data suggest that the geographic range of coccidioidomycosis is expanding as new endemic clusters have been identified in the state of Washington, well outside of the established endemic range. The genetic mechanisms and epidemiological consequences of this expansion are unknown and require better understanding of the population structure and evolutionary history of these pathogens. Here we perform multiple phylogenetic inference and population genomics analyses of 68 new and 18 previously published genomes. The results provide evidence of substantial population structure in C. posadasii and demonstrate presence of distinct geographic clades in central and southern Arizona as well as dispersed populations in Texas, Mexico, South America and Central America. Although a smaller number of C. immitis strains were included in the analyses, some evidence of phylogeographic structure was also detected in this species, which has been historically limited to California and Baja Mexico. Bayesian analyses indicated that C. posadasii is the more ancient of the two species and that Arizona contains the most diverse subpopulations. We propose a southern Arizona-northern Mexico origin for C. posadasii and describe a pathway for dispersal and distribution out of this region.

Genomics↗