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paratuberculosis Infection in Camel (Camelus dromidarius): Current and Prospective Overview

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Open Journal of Veterinary Medicine 2015年第7期5卷 153-160页

作者： Ahmed M. Alluwaimi Department of Microbiology and Parasitology College of Veterinary Medicine King Faisal University Al-Ahsaa Saudi Arabia

Camel (Camelus dromidarius) is an important source of meat and milk and an iconic animal of the Saudi Arabian heritage. The accumulative evidence indicated the spread of paratuberculosis infection in the camel herds. Despite the explicit studies on the details of the disease in camels and methods of its diagnosis, paratuberculosis infection in camels suffers from wide gap of knowledge of the disease pathogenesis, camel immune responses to the infection and factors that enhance camel’s resistance to the infection. The review discusses the current available information of the disease pathobiology and the approaches employed in the diagnosis of paratuberculosis infection in camel. Effective control of the disease in camel prompts for urgent innovation of the current approaches in the diagnosis. Efficient policies and inspection tools are becoming vital to tackle the possible threats of Crohn’s disease to the public health due to the meat and milk consumption.

关键词： Camel Johne’s Disease paratuberculosis Saudi Arabia MAP

Mycobacterium avium subspecies paratuberculosis causes Crohn's disease in some inflammatory bowel disease patients

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World Journal of Gastroenterology 2014年第23期20卷 7403-7415页

作者： Saleh A Naser Sudesh R Sagramsingh Abed S Naser Saisathya Thanigachalam Burnett School of Biomedical Sciences College of MedicineUniversity of Central FloridaOrlandoFL 32816United States

Crohn’s disease(CD)is a chronic inflammatory condition that plagues millions all over the world.This debilitating bowel disease can start in early childhood and continue into late adulthood.Signs and symptoms are usually many and multiple tests are often required for the diagnosis and confirmation of this disease.However,little is still understood about the cause(s)of CD.As a result,several theories have been proposed over the years.One theory in particular is that Mycobacterium avium subspecies paratuberculosis(MAP)is intimately linked to the etiology of CD.This fastidious bacterium also known to cause Johne’s disease in cattle has infected the intestines of animals for years.It is believed that due to the thick,waxy cell wall of MAP it is able to survive the process of pasteurization as well as chemical processes seen in irrigation purification systems.Subsequently meat,dairy products and water serve as key vehicles in the transmission of MAP infection to humans(from farm to fork)who have a genetic predisposition,thus leading to the development of CD.The challenges faced in culturing this bacterium from CD are many.Examples include its extreme slow growth,lack of cell wall,low abundance,and its mycobactin dependency.In this review article,data from 60 studies showing the detection and isolation of MAP by PCR and culture techniques have been reviewed.Although this review may not be 100%comprehensive of all studies,clearly the majority of the studies overwhelmingly and definitively support the role of MAP in at least30%-50%of CD patients.It is very possible that lack of detection of MAP from some CD patients may be due to the absence of MAP role in these patients.The latter statement is conditional on utilization of methodology appropriate for detection of human MAP strains.Ultimately,stratification of CD and inflammatory bowel disease patients for the presence or absence of MAP is necessary for appropriate and effective treatment which may lead to a cure.

关键词： Mycobacterium paratuberculosis Crohn’s disease Cul

On deaf ears, Mycobacterium avium paratuberculosis in pathogenesis Crohn's and other diseases

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World Journal of Gastroenterology 2015年第48期21卷 13411-13417页

作者： William C Davis Department Veterinary Microbiology and Pathology College of Veterinary MedicineWashington State University

The historic suggestion that Mycobacterium avium subsp. paratuberculosis(Map) might be a zoonotic pathogen was based on the apparent similarity of lesions in the intestine of patients with Crohn's disease(CD) with those present in cattle infected with Map, the etiological agent of Johne's disease. Reluctance to fully explore this possibility has been attributed to the difficulty in demonstrating the presence of Map in tissues from patients with CD. Advances in technology have resolved this problem and revealed the presence of Map in a significant proportion of patients with CD and other diseases. The seminal finding from recent investigations, however, is the detection of Map in healthy individuals with no clinical signs of disease. The latter observation indicates all humans are susceptible to infection with Map and lends support to the thesis that Map is zoonotic, with a latent stage of infection similar to tuberculosis, where infection leads to the development of an immune response that controls but does not eliminate the pathogen. This clarifies one of the reasons why it has been so difficult to document that Map is zoonotic and associated with the pathogenesis of CD and other diseases. As discussed in the present review, a better understanding of the immune response to Map is needed to determine how infection is usually kept under immune control during the latent stage of infection and elucidate the triggering events that lead to disease progression in the natural host and pathogenesis of CD and immune related diseases in humans.

关键词： Crohn's disease Johne's disease Mycobacteriumavium subsp. paratuberculosis Animal model Monoclonalantibodies Flow cytometry Cytokines

Mycobacterium avium subspecies paratuberculosis in the etiology of Crohn's disease, cause or epiphenomenon?

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World Journal of Gastroenterology 2014年第36期20卷 13060-13070页

作者： Elisa Liverani Eleonora Scaioli Carla Cardamone Paola Dal Monte Andrea Belluzzi Gastroenterology Division Department of Medical and Surgical Sciences Sant’Orsola-Malpighi University Hospital 40138 Bologna Italy Diagnostic and Speciality Medicine Department of Experimental Microbiology Unit Sant’Orsola-Malpighi University Hospital 40138 Bologna Italy

The origin of inflammatory bowel disease is unknown. Attempts have been made to isolate a microorganism that could explain the onset of inflammation, but no pathological agent has ever been identified. Johne's disease is a granulomatous chronic enteritis of cattle and sheep caused by Mycobacterium avium subspecies paratuberculosis(MAP) and shows some analogies with Crohn's disease(CD). Several studies have tried to clarify if MAP has a role in the etiology of CD. The present article provides an overview of the evidence in favor and against the "MAP-hypothesis", analyzing the methods commonly adopted to detect MAP and the role of antimycobacterial therapy in patients with inflammatory bowel disease. Studies were identified through the electronic database, MEDLINE, and were selected based on their relevance to the objective of the review. The presence of MAP was investigated using multiple diagnostic methods for MAP detection and in different tissue samples from patients affected by CD or ulcerative colitis and in healthy controls. On the basis of their studies, several authors support a close relationship between MAP and CD. Although increasing evidence of MAP detection in CD patients is unquestionable, a clear etiological link still needs to be proven.

关键词： Mycobacterium avium paratuberculosis Crohn’s disea

Survival mechanisms of Mycobacterium aviumsubspecies paratuberculosiswithin host species and in the environment—A review

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Natural Science 2013年第6期5卷 710-723页

作者： Shoor Vir Singh Ajay Vir Singh Avnish Kumar Pravin Kumar Singh Rajib Deb Amit Kumar Verma Amit Kumar Ruchi Tiwari Sandip Chakraborty Kuldeep Dhama Animal Genetics and Breeding Project Directorate on Cattle Indian Council of Agricultural Research Meerut India Animal Resource Development Department Pt. Nehru Complex Agartala India Department of Microbiology & Immunology Uttar Pradesh Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Go-Anusandhan Sansthan (DUVASU) Mathura India Department of Veterinary Epidemiology & Preventive Medicine Uttar Pradesh Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vi- gyan Vishwavidyalaya Evam Go-Anusandhan Sansthan (DUVASU) Mathura India Division of Pathology Indian Veterinary Research Institute (IVRI) Bareilly India Microbiology Laboratory Animal Health Division Central Institute for Research on Goats (CIRG) Mathura India National JALMA Institute for Leprosy and Other Mycobacterial Diseases (NJIL and OMD) Agra India

Mycobacterium avium subsp. paratuberculosis causes chronic inflammation of the intestine known as Johne’s disease (JD) in domestic and wild ruminants including primates. MAP has also been associated with inflammatory bowel disease (IBD) so called Crohn’s disease (CD) of human beings, which is incurable even after surgery. By virtue of the pasteurization resistant power, high endemicity of the infection in animals continues to be the permanent source of infection to human population. High bio-burden of MAP in wide range of biotic (animal hosts including human beings) and abiotic environment in each and every country where it has been investigated, serves a reminder about the survival abilities of the MAP in diverse range of environmental conditions. Ability of the MAP to evade immune system of the host and the temporal events during infection of the macro-phages, is an area of major concern and research activities as the pattern of distribution are quiet different from those of other pathogenic intracellular organisms. Moreover, the organism can survive over a wide range of environmental conditions such as high and low environmental temperatures, pasteurization, low pH, and high salt concentration etc. This superior survival efficiency from environmental degradation and dormancy within host allows the pathogen to be available for causing disease and pathogenicity in animals and human beings, when conditions are favorable. Perusal of literature reveal that, despite the availability of whole genome sequence of MAP, a very little is known about the replication, persistence and survival mechanisms of this pathogen. Therefore, this review tries to address the survival mechanisms of Mycobacterium avium subspecies paratuberculosis in the different host species and adverse environmental conditions in order to allow designing of more rational diagnostic and control procedures.

关键词： paratuberculosis Johne’s Disease Reservoir Disease Survival MAP Animal

Mycobacterium avium subspecies paratuberculosis—An environmental trigger of type 1 diabetes mellitus

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Journal of Diabetes Mellitus 2012年第1期2卷 88-95页

作者： Coad Thomas Dow Eye Research Institute University of Wisconsin-Madison Madison USA

Type 1 diabetes mellitus (T1DM) is an autoimmune disease. The etiology of T1DM is incompletely understood but environmental agent(s) are thought to trigger T1DM in the genetically at-risk. Humans are widely exposed to Mycobacterium avium subspecies paratuberculosis (MAP), a proven multi-host chronic enteric pathogen that is mostly studied in ruminant animals and causes the inflammatory disease paratuberculosis or Johne’s disease. In humans, MAP is the putative cause of Crohn’s disease and has been linked to sarcoidosis, autoimmune thyroiditis, multiple sclerosis and autoimmune diabetes. The role of MAP as a trigger for T1DM was first postulated in 2005;subsequent studies suggest a link. This article discusses MAP, human exposure to MAP, genetic susceptibility to MAP and MAP in human disease including T1DM.

关键词： Autoimmune Diabetes T1DM paratuberculosis MAP HSP65 Molecular Mimicry

Evaluation of “Indigenous Vaccine” Developed Using “Indian Bison Type” Genotype of Mycobacterium avium subspecies paratuberculosisStrain “S5” of Goat Origin in a Sheep Flock Endemic for Johne’s Disease: A Three Years Trial in India

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World Journal of Vaccines 2013年第2期3卷 52-59页

作者： Shoor Vir Singh Ajay Vir Singh Pravin Kumar Singh Saurabh Gupta Harendra Singh Brajesh Singh Omalur Rajendran Vinodh Kumar Aripudur Sellappan Rajendiran Narendra Nath Swain Jagdip Singh Sohal Central Institute for Research on Goats Mathura Indi Central Institute for Research on Goats Mathura India Southern Regional Research Centre Central Sheep and Wool Research Institute Kodaikanal India

“Indigenous vaccine” developed from native “Indian Bison Type” strain (“S5”) of Mycobacterium avium subspecies paratuberculosis (MAP) of “goat origin” was first time evaluated in a sheep flock of Bharat Merino breed located in Mannavanur town of Tamil Nadu in South India. Therapeutic efficacy of the vaccine was evaluated for 3 years between 2008 and 2010, on the basis of improvements in productivity (body weights, reproductive efficiency and survivability), physical condition, clinical symptoms (weakness, diarrhea, wool quality), immune response (sero-conversion) and infection load in feces (shedding). After immunization of the flock in 2008, the successive progenies of 112 and 53 lambs born in 2009 and 2010, respectively were vaccinated. Whereas, 40 lambs born to control animals were kept as unvaccinated controls. Though gain in body weights in vaccinated versus controls were not significant in 2008, growth rates were distinctly superior in Ist and IInd generations of vaccinated lambs. Reproductive performance (tupping percent) and survivability of lambs and adult sheep improved significantly. There was overall reduction in yearly morbidity (diarrhea) and mortality rates of the flock in post vaccination years. Shedding of MAP in feces was reduced in vaccinated sheep by 6.2%, 14.3% and 27.3% in 2008, 2009 and 2010 respectively, whereas shedding increased in the control sheep. Seromonitoring of the animals by “indigenous ELISA kit” showed enhanced “flock immunity” in successive generations. “Indigenous vaccine” reduced clinical disease and shedding and improved immunity and productivity of Bharat Merino flock, endemic for Johne’s disease.

关键词： paratuberculosis Indigenous Vaccine Indian Bison Type Bharat Merino Sheep India

Evaluation of a Live paratuberculosis Vaccine in Endemically Infected Flocks of Sheep and Goats in Greece

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Journal of Immune Based Therapies, Vaccines and Antimicrobials 2013年第4期2卷 49-58页

作者： Zoi Dimareli-Malli George Papadopoulos Panagiotis Betsas Veterinary Institute of Infectious and Parasitic Diseases of Thessaloniki Ministry of Rural Development and Food Greece Veterinary Research Institute of Thessaloniki NAGREF Thermi Thessaloniki Greece

A large 7-year vaccination trial was conducted in 15 flocks of goats and 7 flocks of sheep, known to be infected with Mycobacterium avium subsp. paratuberculosis (MAP), in Northern Greece. A total of 3665 kids and 1685 lambs, 7 - 30 days old, were vaccinated during 1995-1999. Seven hundred and seventy-five kids and 413 lambs were kept as unvaccinated controls. For each trial, the Incidence Rate Ratio (IRR), with respective exact 95% confidence intervals, was calculated. All IRR point estimates for young animals were very large (from 5.68 to 11.78 for kids and from 4.28 to 10.08 for lambs), while none of the 95% confidence intervals included 1. The protective effect of vaccination was large and the difference in mortality among vaccinated and unvaccinated animals was more pronounced in young animals. The effect in adult animals was smaller than in young animals;it was, however, still considerable. Upon visual inspection of the K-M curves, it seems that for the young animal trials the vaccinated and control-group curves were diverging increasingly over time, which indicates that the gain from the vaccination (or the loss from non-vaccination) might increase over time during the trial.

关键词： paratuberculosis Vaccination Sheep Goats Protective Effect

The 19 kDa Protein from Mycobacterium avium subspecies paratuberculosisIs a Glycolipoprotein

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Advances in Microbiology 2013年第7期3卷 520-528页

作者： Saleh A. Naser Saisathya Thanigachalam Natalia Spinelli Mitra M. Safavi Najih Naser Omar Khan BioSynse Cary US Burnett School of Biomedical Sciences College of Medicine University of Central Florida Orlando USA

This study characterizes the 19 kDa protein expressed by Mycobacterium avium subspecies paratuberculosis (MAP) as a glycolipoprotein, providing the foundation for future experiments regarding its antigenicity and role in disease pathogenicity. We have previously shown that a 4.8 kb insert from MAP will produce a 16 kDa recombinant protein when expressed in Escherichia coli and 19 kDa recombinant protein when expressed in M. smegmatis (smeg19K). The difference of 3 kDa in size of these expressed proteins may be related to post translational modifications that occur in Mycobacterium species. We hypothesized that smeg19K is a glycolipoprotein since BLAST analysis revealed approximately 76% amino acid identity between the MAP 19 kDa protein and a known lipoglycoprotein, the 19 kDa protein of M. tuberculosis. This prediction was confirmed by the following positive staining of smeg19K with Sudan Black 4B, a postelectrophoresis dye used to stain for lipids. Smeg19K has also stained positively for glycosylation with the lectin concavalin A, a highly specific stain for mannose residues. As expected, treatment with tunicamycin (an antibiotic known to inhibit N-glycosylation) and treatment with deglycosylation assay (non-specific for mannose), showed no reduction in size of 19 kDa glycolipoprotein.

关键词： Mycobacterium Avium Subspecies paratuberculosis Glycolipoprotein 19 KDa Protein Post Translational Modification