5 fold) under iron-replete conditions in C MAP strain (Figure 3B). Discussion Johne’s disease is a major animal health problem of ruminant species worldwide and imposes significant economic losses to the industry. Our ability to culture the causative agent–Mycobacterium avium

Vactosertib subsp. paratuberculosis (MAP)–and therefore its rapid diagnosis and our understanding of its virulence is limited. MAP is difficult to culture because of its unusually strict iron requirements. For optimal growth in laboratory media, MAP requires a siderophore (mycobactin) supplementation that makes MAP fastidious [39]., often requiring eight to sixteen weeks to produce colonies in culture – a major hurdle in the diagnosis and therefore implementation of optimal control measures. Understanding iron regulatory networks in the pathogen invitro is therefore of great importance. A tale of two strain types of MAP – A case to study iron regulation Several microbiological and genotyping studies and clinical observations suggest that Johne’s in certain hosts such as sheep, goats, deer, and bison is caused by a distinct set of strains that show a relatively high degree of host preference [18, 40]. At least two microbiologically distinct types of MAP have been recognized. A less readily cultivable type is the common, but not invariable, cause of Selleckchem MDV3100 paratuberculosis in sheep (S MAP) [39, 41, 42], while

another readily cultivable type is the most common cause of the disease in ZD1839 cattle (C MAP). Cell infection

studies have also revealed distinctive host response phenotypes between cattle and sheep MAP strains – the former elicit primarily a pro-inflammatory response while latter strains suppress inflammation and upregulate anti-apoptotic pathways [24, 25]. In addition, since MAP genome sequence was published in 2005, very little research has focused on iron physiology and its contribution to metabolic networks of this fastidious organism. Based on these classical microbiologic, Cell press genotypic, and clinical observations, we addressed the hypothesis that the iron dependent gene regulation is different between cattle and sheep MAP strains using a systems approach. Iron-sparing response to iron-limitation is unique to cattle MAP strain Iron is a critical component of several metabolic enzymes [43]. Most bacteria respond to iron starvation with a unique regulatory mechanism called the iron-sparing response [35]. Iron-sparing is a physiological phenomenon used by cells to increase the intracellular iron pool by post-transcriptionally repressing the synthesis of non-essential iron using proteins and sparing iron for essential cellular functions [44]. Therefore, the paradigm is to transcriptionally upregulate all iron uptake systems while repressing non-essential enzymes via post-transcriptional regulatory mechanisms to survive iron-limiting conditions.