Proceedings of the 10th International Colloquium on Paratuberculosis

Pathogenomics and MAP Biology Perspectives Lecture
MAP Biology Perspectives.
Luiz E Bermudez.
College <strong>of</strong> Veterinary Medicine, Oregon State University, Corvallis, OR.
Mycobacterium avium subsp paratuberculosis (MAP) causes Johne’s disease. It is encountered in <strong>the</strong>
environment as well infecting ruminants. The organism is acquired at <strong>the</strong> calf stage, and for several years <strong>the</strong>
infection evolves, triggering clinical signs <strong>of</strong> <strong>the</strong> disease. We know very little about sources <strong>of</strong> infection, ability
to survive in <strong>the</strong> ruminant’s rumen, about crossing <strong>of</strong> <strong>the</strong> intestinal barrier and interaction with <strong>the</strong> host immune
system, both when immature and mature. It is assumed that MAP lives and replicates in macrophages but
<strong>the</strong> possible role <strong>of</strong> o<strong>the</strong>r host cells is not well understood. What kind <strong>of</strong> nutrients <strong>the</strong> pathogen needs when
inside phagocytic cells, and how it influence <strong>the</strong> intracellular lifestyle is unknown. The importance <strong>of</strong> <strong>the</strong> innate
and adaptive immunity in host defense and how MAP subvert <strong>the</strong>m are key questions for which we have few
answers. So, how do <strong>the</strong> papers presented at <strong>the</strong> meeting add to our knowledge? The concept <strong>of</strong> bi<strong>of</strong>ilm is
an obvious one, but <strong>the</strong> role <strong>of</strong> bi<strong>of</strong>ilm in transmission has not been investigated. The studies <strong>of</strong> <strong>the</strong> MAP
transcriptome in macrophages. Encouraging first steps to understand how <strong>the</strong> pathogen manage to live inside
<strong>of</strong> a phagocyte. The comparison with better studied Mycobacteria can help significantly in <strong>the</strong> understanding <strong>of</strong>
MAP pathogenesis. The role <strong>of</strong> MAP lipids in <strong>the</strong> pathogenesis <strong>of</strong> <strong>the</strong> infection. Very difficult topic to address,
but <strong>of</strong> remarkable importance. Novel findings are beginning to add important pieces to out knowledge gap.
Role <strong>of</strong> iron and gene regulation in MAP. Here too, a significant topic that would benefit from past findings
using different mycobacteria. Shedding is an enigmatic topic. Host-mediated or pathogen-triggered? Much
work needs to be done, but <strong>the</strong> value <strong>of</strong> <strong>the</strong> finding can have significant impact on transmission. Proteomic
analysis, as well as cell wall protein analysis can unveil crucial understanding on how MAP interacts with <strong>the</strong>
intracellular environment. Many <strong>of</strong> <strong>the</strong>se studies are bringing some new excitement to <strong>the</strong> field, but we need to
start asking specific questions related to <strong>the</strong> biology <strong>of</strong> <strong>the</strong> organism as well <strong>the</strong> pathogenesis <strong>of</strong> <strong>the</strong> infection.
A move from <strong>the</strong> general information to <strong>the</strong> specific observation that might impact prevention or treatment <strong>of</strong>
<strong>the</strong> disease. We all have heard that <strong>the</strong>se are golden times for biology, but we need to be creative and use <strong>the</strong>
techniques that are available to us to ask relevant questions, create animal models that would allow us to test
important hypo<strong>the</strong>sis and provide precise answers without <strong>the</strong> complexity <strong>of</strong> <strong>the</strong> natural host. In summary, <strong>the</strong>
field is positioned for a dynamic “beginning”, but major challenges are ahead <strong>of</strong> us.
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