PMID- 28611468 OWN - NLM STAT- MEDLINE DCOM- 20190206 LR - 20240326 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 IP - 1 DP - 2017 Jun 13 TI - Insights into enterotoxigenic Escherichia coli diversity in Bangladesh utilizing genomic epidemiology. PG - 3402 LID - 10.1038/s41598-017-03631-x [doi] LID - 3402 AB - Enterotoxigenic Escherichia coli (ETEC) cause more than 500,000 deaths each year in the developing world and are characterized on a molecular level by the presence of genes that encode the heat-stable (ST) and/or heat-labile (LT) enterotoxins, as well as surface structures, known as colonization factors (CFs). Genome sequencing and comparative genomic analyses of 94 previously uncharacterized ETEC isolates demonstrated remarkable genomic diversity, with 28 distinct sequence types identified in three phylogenomic groups. Interestingly, there is a correlation between the genomic sequence type and virulence factor profiles based on prevalence of the isolate, suggesting that there is an optimal combination of genetic factors required for survival, virulence and transmission in the most successful clones. A large-scale BLAST score ratio (LS-BSR) analysis was further applied to identify ETEC-specific genomic regions when compared to non-ETEC genomes, as well as genes that are more associated with clinical presentations or other genotypic markers. Of the strains examined, 21 of 94 ETEC isolates lacked any previously identified CF. Homology searches with the structural subunits of known CFs identified 6 new putative CF variants. These studies provide a roadmap to exploit genomic analyses by directing investigations of pathogenesis, virulence regulation and vaccine development. FAU - Sahl, Jason W AU - Sahl JW AD - Institute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, 801 W. Baltimore Street, Suite 600, Baltimore, MD, 21201, USA. AD - Translational Genomics Research Institute, Flagstaff, AZ, 86001, USA. FAU - Sistrunk, Jeticia R AU - Sistrunk JR AUID- ORCID: 0000-0001-9129-6529 AD - Institute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, 801 W. Baltimore Street, Suite 600, Baltimore, MD, 21201, USA. FAU - Baby, Nabilah Ibnat AU - Baby NI AD - Centre for Vaccine Sciences, Immunology Laboratory, International Centre Center for Diarrhoeal Disease Research, Mohakhali, Dhaka, 1212, Bangladesh. FAU - Begum, Yasmin AU - Begum Y AD - Centre for Vaccine Sciences, Immunology Laboratory, International Centre Center for Diarrhoeal Disease Research, Mohakhali, Dhaka, 1212, Bangladesh. FAU - Luo, Qingwei AU - Luo Q AD - Department of Medicine, Division of Infectious Diseases, Washington, USA. FAU - Sheikh, Alaullah AU - Sheikh A AUID- ORCID: 0000-0002-2972-6978 AD - Centre for Vaccine Sciences, Immunology Laboratory, International Centre Center for Diarrhoeal Disease Research, Mohakhali, Dhaka, 1212, Bangladesh. AD - The Molecular Microbiology and Microbial Pathogenesis Program, Division of Biology and Biomedical Sciences, Washington University in St. Louis, Washington, USA. FAU - Qadri, Firdausi AU - Qadri F AD - Centre for Vaccine Sciences, Immunology Laboratory, International Centre Center for Diarrhoeal Disease Research, Mohakhali, Dhaka, 1212, Bangladesh. FAU - Fleckenstein, James M AU - Fleckenstein JM AD - Department of Medicine, Division of Infectious Diseases, Washington, USA. AD - The Molecular Microbiology and Microbial Pathogenesis Program, Division of Biology and Biomedical Sciences, Washington University in St. Louis, Washington, USA. AD - Medicine Service, Veterans Affairs Medical Center, St. Louis, MO, USA. FAU - Rasko, David A AU - Rasko DA AD - Institute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, 801 W. Baltimore Street, Suite 600, Baltimore, MD, 21201, USA. drasko@som.umaryland.edu. LA - eng GR - I01 BX001469/BX/BLRD VA/United States GR - R01 AI089894/AI/NIAID NIH HHS/United States GR - R01 AI126887/AI/NIAID NIH HHS/United States GR - HHSN272200900009C/AI/NIAID NIH HHS/United States GR - U19 AI090873/AI/NIAID NIH HHS/United States GR - T32 AI095190/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20170613 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (DNA, Bacterial) RN - 0 (Escherichia coli Proteins) RN - 0 (Virulence Factors) SB - IM MH - Bangladesh/epidemiology MH - Case-Control Studies MH - DNA, Bacterial MH - Diarrhea/epidemiology/*genetics/microbiology MH - Enterotoxigenic Escherichia coli/*pathogenicity MH - Escherichia coli Infections/epidemiology/*genetics/microbiology MH - Escherichia coli Proteins/*genetics MH - *Genetic Variation MH - Genomics/*methods MH - Genotype MH - Humans MH - Phylogeny MH - Virulence Factors/*genetics PMC - PMC5469772 COIS- The authors declare that they have no competing interests. EDAT- 2017/06/15 06:00 MHDA- 2019/02/07 06:00 PMCR- 2017/06/13 CRDT- 2017/06/15 06:00 PHST- 2017/01/19 00:00 [received] PHST- 2017/04/28 00:00 [accepted] PHST- 2017/06/15 06:00 [entrez] PHST- 2017/06/15 06:00 [pubmed] PHST- 2019/02/07 06:00 [medline] PHST- 2017/06/13 00:00 [pmc-release] AID - 10.1038/s41598-017-03631-x [pii] AID - 3631 [pii] AID - 10.1038/s41598-017-03631-x [doi] PST - epublish SO - Sci Rep. 2017 Jun 13;7(1):3402. doi: 10.1038/s41598-017-03631-x.