Protein Kinase G Induces an Immune Response in Cows Exposed to Mycobacterium avium Subsp. paratuberculosis.

Horacio Bach,Melissa Richard-Greenblatt,Greg Keefe,Douglas J Begg,Wanika Lai,Marcelo Chaffer,Eviatar Bach

doi:10.1155/2018/1450828

Abstract

To establish infection, pathogens secrete virulence factors, such as protein kinases and phosphatases, to modulate the signal transduction pathways used by host cells to initiate immune response. The protein MAP3893c is annotated in the genome sequence of Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne's disease, as the serine/threonine protein kinase G (PknG). In this work, we report that PknG is a functional kinase that is secreted within macrophages at early stages of infection. The antigen is able to induce an immune response from cattle exposed to MAP in the form of interferon gamma production after stimulation of whole blood with PknG. These findings suggest that PknG may contribute to the pathogenesis of MAP by phosphorylating macrophage signalling and/or adaptor molecules as observed with other pathogenic mycobacterial species.

Highlights

Each year the dairy industry suffers significant economic losses from the infectious agent Mycobacterium avium subspecies paratuberculosis (MAP) [1]
In the current study we demonstrate that MAP3893c, which is annotated in the MAP genome for protein kinase G (PknG), encodes for a functional kinase that is secreted upon infection of human macrophage cells
In the current study we demonstrated that the open reading frame MAP3893c, a homolog of PknG in mycobacteria, encodes for an active kinase that is secreted during infection

Summary

Introduction

Each year the dairy industry suffers significant economic losses from the infectious agent Mycobacterium avium subspecies paratuberculosis (MAP) [1]. The bacterium causes cattle and other ruminants a fatal gastrointestinal disease known as Johne’s disease (JD). The National Animal Health Monitoring System estimates the prevalence of JD in US dairy herds at 68% [2]. Animals can remain asymptomatic for many years and shed large numbers of the bacteria in their faeces resulting in a transmission via faecal–oral route to many other cattle before the appearance of any clinical presentation in the herd [3]. The presence of MAP in dairy products [4, 5] represents a potential concern to human health. Recent advances in diagnostics have enabled the isolation of MAP from intestinal tissues [6], blood [7, 8], and breast milk [9] of

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Conclusion