Transcriptional and epigenomic landscape of Bordetella hinzii human host adaptation

Authors

• J Rhee
• VC Chang
• I Cheng
• AM Calafat
• JC Botelho
• JJ Shearer
• JN Sampson
• VW Sfetiawan
• LR Wilkens
• DT Silverman
• MP Purdue
• JN Hofmann

Abstract

Bordetella hinzii is an emerging zoonotic pathogen that infects immunocompromised human hosts. Previous work in the lab reported genomic analysis of 25 isolates cultured over a period of 45 months from a patient with germline IL-12Rβ1 deficiency and persistent blood and GI tract infection with B. hinzii. These isolates demonstrated striking phenotypic diversity and were shown to have descended from a clonal lineage with extensive genomic diversification due to an inactivating E9G substitution in the DNA polymerase III ε- proofreading subunit (DnaQ) resulting in proofreading-deficient hypermutation. In this work, we evaluate the transcriptional and epigenomic landscape of these isolates to understand how mutations selected during infection reprogramed gene expression. Our study reveals four main observations. 1) Genes involved in flagellar biosynthesis appeared to be convergently downregulated in the DnaQ E9G lineages and a DnaQ WT isolate, suggesting a potential evolutionary tradeoff between motility and host immune escape. 2) Two isolates that shared a stop gain mutation in a Type III specific methyltransferase exhibited loss of methylation in a type III motif. Loss of methylation at this motif, present 2282 times throughout the genome, represents a global change in epigenetic state, with predicted global transcriptional changes and potential fitness consequences, to be tested. 3) Each isolate displayed unique transcriptional pattern, but shared general functional patterns as classified by gene ontology. 4) A putative phage, phiEt88, demonstrated variable expression across isolates. Overall, our study demonstrates that remarkable transcriptional diversity evolved during host adaptation with evidence of potential convergent evolution.

Scientific Focus Area: Microbiology and Infectious Diseases

This page was last updated on Monday, September 25, 2023