Host-Mycobacterium avium subsp. paratuberculosis interactome reveals a novel iron assimilation mechanism linked to nitric oxide stress during early infection

Elise A Lamont, Wayne W. Xu, Srinand Sreevatsan

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Background: The initial interaction between host cell and pathogen sets the stage for the ensuing infection and ultimately determine the course of disease. However, there is limited knowledge of the transcripts utilized by host and pathogen and how they may impact one another during this critical step. The purpose of this study was to create a host-Mycobacterium avium subsp. paratuberculosis (MAP) interactome for early infection in an epithelium-macrophage co-culture system using RNA-seq.Results: Establishment of the host-MAP interactome revealed a novel iron assimilation system for carboxymycobactin. Iron assimilation is linked to nitric oxide synthase-2 production by the host and subsequent nitric oxide buildup. Iron limitation as well as nitric oxide is a prompt for MAP to enter into an iron sequestration program. This new iron sequestration program provides an explanation for mycobactin independence in some MAP strains grown in vitro as well as during infection within the host cell. Utilization of such a pathway is likely to aid MAP establishment and long-term survival within the host.Conclusions: The host-MAP interactome identified a number of metabolic, DNA repair and virulence genes worthy for consideration as novel drug targets as well as future pathogenesis studies. Reported interactome data may also be utilized to conduct focused, hypothesis-driven research. Co-culture of uninfected bovine epithelial cells (MAC-T) and primary bovine macrophages creates a tolerant genotype as demonstrated by downregulation of inflammatory pathways. This co-culture system may serve as a model to investigate other bovine enteric pathogens.

Original languageEnglish (US)
Article number694
JournalBMC Genomics
Issue number1
StatePublished - Oct 10 2013

Bibliographical note

Funding Information:
EAL performed experiments. EAL, WWX, and SS analyzed and interpreted data. EAL and SS wrote the paper. SS provided financial support. All authors read and approved the final manuscript.


  • Bovine
  • Co-culture
  • Epithelium
  • Interactome
  • Iron
  • Johne's disease
  • Macrophage
  • Mycobacteria
  • Mycobacterium avium subsp. paratuberculosis
  • RNA-seq


Dive into the research topics of 'Host-Mycobacterium avium subsp. paratuberculosis interactome reveals a novel iron assimilation mechanism linked to nitric oxide stress during early infection'. Together they form a unique fingerprint.

Cite this