Major Funded Projects:
A project currently funded in the laboratory is under the Genomic Centers for Infectious Diseases (U19) awarded to the Institute for Genome Sciences at the University of Maryland entitled the “Host, Pathogen, and the Microbiome: Determinants of Infectious Disease Outcomes”. The Rasko lab has a leading role in the Microbial Project titled “Examination of Enteric Pathogens with Multi-Omic Approaches” where we are examining the pathogen populations, microbiome and metagenomic and metatranscriptomic samples from two human challenege studies that were conducted at the University of Maryland on either enterotoxignic E. coli or Vibrio cholerae. These will be some of the first studies to examine these pathogens in samples from humans to directly examine the impact of these pathogens on the microbiome and hosts.
Please refer to the website on the IGS homepage for descriptions of other projects and available data.
Projects by Organism:
The Rasko lab has been working on enterotoxigenic E. coli (ETEC) since its inception in 2008, and even before that with the publishing of the first and second ETEC genomes, E24377a and B7A in 2008 (Rasko I&I, 2008). Those initial studies were extended in 2011 to include a number of additional ETEC references (Sahl et al, I&I, 2011) and further extended in collaborative projects with the Wellcome Trust Sanger Institute which resulted in a publication in Nature Genetics by von Mentzer et al. Further work on the genomics of ETEC in a collection from Bangladesh identified that multiple isolates can be identified in individual subjects, resulting in it being very difficult to assign which isolate may be the actual etiological agent. The paper describing this variation can be found here.
We are continuing to examine the variation among ETEC isolates from human samples, see the description of the GCID project above. Within that project we have the opportunity to examine variation as the pathogen travels through the host. This work is underway and stay tuned for future publications.
AEECs (EPEC & EHEC)
In 2013 we published a study describing the genomes of 114 attaching and effacing E. coli (AEEC) in PNAS that can be found here. This study included newly sequenced genomes of enteropathogenic E. coli (EPEC) and also O157:H7 and non-O157 enterohemorrhagic E. coli (EHEC). Also, as an aim of the UMB ERIN CRC Project lead by Dr. James Kaper we investigated the genomic diversity of typical EPEC from study sites in the Global Enteric Multicenter Study (GEMS). This resulted in a manuscript published in Nature Microbiology in 2016, located here. Following these studies we used comparative genomics to investigate the diversity of the AEEC virulence plasmids in a study that can be found here.
The Rasko Lab, in collaboration with researchers at the FDA and University of Florida, recently published a paper describing enteroinvasive E. coli (EIEC) genomes compared with representative Shigella genomes. This analysis identified three distinct clades of EIEC that can be used as references of EIEC genome diversity. The paper can be found here.
Shigella species isolates have long been suggested to be close relatives to E. coli. We demonstrated in a paper by Sahl et al. that Shigella isolates have evolved from E. coli in approximately 3 radiations, but not necessarily only three times. The genomic differences in global collections of Shigella isolates were cataloged and could be used as a molecular diagnostic for the Shigella species into different genomic groups.
We also recently characterized a collection of S. boydii genomes, which had not been examined in detail previously. The majority of those isolates were obtained from the Global Enteric Multicenter Study (GEMS) collection and to date represent the largest collection of S. boydii isolates to be examined. The paper can be found here.
In addition to the genomic comparisons we also demonstrated the utility of combining genomics and transcriptomics into the study of the pathogenesis of these organisms. We identified genes that were genomically common in the S. flexneri and expressed in a series of microarray and RNA-seq experiments. This gene was identified as a growth regulator and was characterized though classic microbial pathogenesis and identified to be a negative regulator of multiple virulence genes and pathways. This important paper can be found here.
Ongoing Shigella work includes the further examination of isolates from the Global Enteric Multicenter Study (GEMS) sites and comparative genomics and trascnriptomics among the isolates of this important human pathogen.
As with many other groups we have expanded our studies onto the global problem of antimicrobial resistance. Our early genomic studies have focused on Klebsiella species and their evolution, as well as a collection of >200 Acinetobacter baumanii isolates from the University of Maryland Medical Center. These papers can be found on the publications pages here.
Additional transcriptional and functional studies are being followed up on in the lab. Stay tuned for future publications on these topics.