843. Comparative genomics and assessment of strain diversity, pathogenicity and transmission of C. difficile isolates from a hospital setting
Session: Oral Abstract Session: Clostridium difficile
Thursday, October 27, 2016: 3:15 PM
Room: 388-390
Background: C. difficile infection (CDI) is a critical issue in hospitals worldwide. Understanding the highly dynamic C. difficile genome is a key priority, however, most current methods for evaluating CDI genetic diversity rely on short-read sequencing and reference mapping. These methods miss many features impacting virulence such as genome rearrangements, epigenetic markers of regulation, as well as horizontally transferred genes, prophages, and plasmids. Here, we undertake the most comprehensive analysis of complete C. difficile genomes to date, by comparing long-read genome assemblies of over 50 hospital strains. Methods: All isolates were deep sequenced using PacBio long reads. Genomes were assembled and annotated for genes, phages, plasmids, mobile elements, epigenetic motifs, and MLST type using the PathogenDB-pipeline, and manually curated to yield finished genomes. The curated set of genomes was then used for comparative analysis including phylogenetics, assignment of gene gain/loss, differential epigenetic patterns, and resolution of structural rearrangements. Results: We sequenced a phylogenetically diverse cross-sections of C. difficile and identified potential cases of transmission. Surprisingly, phylogenetic groupings did not strictly correspond with epigenomic and antibiotic signatures, with some epigenetic motifs and antibiotic resistance genes crossing (or splitting) known MLST types. Additionally, multiple structural changes (e.g. deletions and insertions) impacting genes were seen across genomes and within MLST types (Fig 1).
Conclusion: CDI causing C. difficile has tremendous genomic variability, much of which cannot be observed using traditional sequencing approaches, which may be associated to transmission, infection and increased pathogenicity.
Figure 1: C. difficile genomic variation. A) Rearrangements among representatives from different strains. B) Structural variants and SNVs in NAP1 isolates.
Elizabeth Webster, BS1, Kieran Chacko, BA, BS1, Mitchell Sullivan, PhD1, Theodore Pak, AB1, Brianne Ciferri, MPH1, Colleen Beckford, MS1, Martha Lewis, BS1, Gang Fang, PhD1, Deena Altman, MD2, Camille Hamula, PhD3, Shirish Huprikar, MD4, Robert Sebra, Ph.D.1, Eric Schadt, PhD1, Andrew Kasarskis, PhD1, Harm Van Bakel, PhD1 and Ali Bashir, PhD1, (1)Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, (2)Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, (3)Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, (4)The Mount Sinai Hospital, New York, NY

Disclosures:

E. Webster, None

K. Chacko, None

M. Sullivan, None

T. Pak, None

B. Ciferri, None

C. Beckford, None

M. Lewis, None

G. Fang, None

D. Altman, None

C. Hamula, None

S. Huprikar, None

R. Sebra, None

E. Schadt, None

A. Kasarskis, None

H. Van Bakel, None

A. Bashir, None

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