Mycobacterium avium subspecies paratuberculosis and Crohn's disease: a systematic review and meta-analysis

Feller, Martin; Huwiler, Karin; Stephan, Robert M.; Altpeter, Ekkehardt; Shang, Aijing; Furrer, Hansjakob; Pfyffer, Gaby E.; Jemmi, T.; Baumgärtner, A.; Egger, Matthias

doi:10.1016/s1473-3099(07)70211-6

Cited by 459 publications

(346 citation statements)

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“…avium subsp. paratuberculosis is the causative organism of Johne's disease (paratuberculosis), a debilitating chronic enteritis in ruminants (49), and has been implicated in Crohn's disease in humans (18). M. avium subsp.…”

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Genomic Comparison of PE and PPE Genes in the Mycobacterium avium Complex

et al. 2009

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The Mycobacterium avium complex (MAC) comprises genomically similar but phenotypically divergent bacteria that inhabit diverse environments and that cause disease in different hosts. In this study, a wholegenome approach was used to examine the polymorphic PE (Pro-Glu) and PPE (Pro-Pro-Glu) gene families, implicated in immunostimulation and virulence. The four major groups of MAC organisms were examined, including the newly sequenced type strains of M. intracellulare and M. avium subsp. avium, plus M. avium subsp. paratuberculosis and M. avium subsp. hominissuis, for the purpose of finding genetic differences that could be exploited to design diagnostic tests specific to these groups and that could help explain their divergence in pathogenesis and host specificity. Unique and missing PPE genes were found in all MAC members except M. avium subsp. avium. Only M. intracellulare had a unique PE gene. Apart from this, most PE and PPE sequences were conserved, with average nucleotide sequence identities of 99.1 and 98.1%, respectively, among the M. avium subspecies, but only 82.9 and 79.7% identities with the PE and PPE sequences of M. intracellulare, respectively. A detailed analysis of the amino acid sequences was performed between M. avium subsp. paratuberculosis and M. avium subsp. hominissuis. Most differences were detected in the PPE proteins, with amino acid substitutions and frame shifts leading to unique amino acid sequences. In conclusion, several unique PPE proteins were identified in MAC organisms next to numerous polymorphisms in both the PE and PPE gene families. These substantial differences could help explain the divergence in phenotypes within the MAC and could lead to diagnostic tests with better discriminatory abilities.Mycobacterium avium and Mycobacterium intracellulare are collectively known as the Mycobacterium avium complex (MAC). For genotypic, phenotypic, and historical reasons, multiple subspecies of M. avium are recognized; these include Mycobacterium avium subsp. paratuberculosis, M. avium subsp. hominissuis, Mycobacterium avium subsp. avium, and M. avium subsp. silvaticum (50). All four M. avium subspecies and M. intracellulare possess a high degree of genetic similarity but are capable of infecting a diverse range of host species.M. avium subsp. paratuberculosis is the causative organism of Johne's disease (paratuberculosis), a debilitating chronic enteritis in ruminants (49), and has been implicated in Crohn's disease in humans (18). M. avium subsp. avium and M. avium subsp. silvaticum are limited almost exclusively to avian species (53), in which they cause tuberculosis. M. avium subsp. hominissuis is a recent designation and was added to reflect the distinction of human and porcine isolates from bird-type strains when genotypic methods showed that M. avium isolates from humans in particular but also pigs rarely shared the genetic profiles of organisms found in birds (38,53). M. avium subsp. hominissuis and M. intracellulare are ubiquitous, saprophytic mycobacteria commonly found in so...

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Genomic Comparison of PE and PPE Genes in the Mycobacterium avium Complex

et al. 2009

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“…Entre los problemas que motivan la controversia, destacan el uso de métodos indirectos para la detección del agente, el escaso número de bacterias observado en los tejidos analizados, la incapacidad de algunos grupos de investigación para identificar este patógeno en pacientes con EC 7 y la existencia de un amplio rango de prevalencias descritas de MAP en seres humanos, que fl uctúan entre 0 y 100% [30][31][32] . Algunos estudios describen el empleo de diversos métodos de diagnóstico (aislamiento, histología, inmunocitoquímica y PCR), en los cuales solamente lograron detectar esta bacteria en tejidos animales utilizados como controles experimentales, pero no en biopsias de personas enfermas 33,34 , lo que podría refl ejar diferencias en los protocolos experimentales empleados para la detección del agente.…”

Section: La Asociación Map-ecunclassified

Mycobacterium avium subsp paratuberculosis y enfermedad de Crohn: evidencias de una zoonosis

et al. 2011

Rev. méd. Chile

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L a paratuberculosis bovina, también conocida como enfermedad de Johne, es una patología causada por la bacteria Mycobacterium avium subsp. paratuberculosis (MAP), que se caracteriza por una lesión intestinal crónica de carácter proliferativa 1 . Debido a las similitudes fi siopatológicas entre la infección de los bovinos y la enfermedad de Crohn (EC) en el humano, una asociación causal del MAP con ambas patologías ha sido sugerida desde hace algunos años, lo que ha generado controversia en la comunidad científi ca relacionada a la transmisión inter-especies 1,2 . En este trabajo se revisan exhaustivamente los hallazgos más representativos y recientes que dan cuenta de esta controversia, y se describen brevemente los antecedentes en Chile que explican la necesidad de realizar estudios en este ámbito. El agenteMAP es un patógeno intracelular facultativo, Gram positivo, ácido alcohol resistente, aerobio y cuya temperatura óptima de crecimiento es 37ºC. Con un tiempo de generación mayor a 20 h, es una bacteria de crecimiento lento que requiere varias semanas de incubación antes que sus colonias sean detectables en los medios de cultivo 1,3,4 . Como las bacterias del género Mycobacterium, MAP posee un genoma rico en nucleótidos G+C y su pared celular tiene un alto contenido de ácidos micólicos. Como característica especie-específi ca destacan su dependencia del sideróforo micobactina para el crecimiento in vitro y la presencia del segmento de inserción IS900 en su genoma, que se ha utilizado para la detección específi ca de este patógeno 1,5 .MAP es capaz de infectar una amplia variedad

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“…Normal autophagy is sufficient in the clearance of this pathogen, but in the absence of functional ATG16L1 and IRGM, adherent-invasive Escherichia coli is able to proliferate [25]. In addition, there has been a positive correlation between the detection of Mycobacterium avium substrain paratuberculosis in biopsies from CD patients as compared with control samples taken from patients with ulcerative colitis [26]. While neither has yet to be directly implicated in the etiology of CD, their persistent presence might explain some of the inflammatory complications that manifest in CD.…”

Section: Vitamin D Nod2 Cd and Autophagymentioning

confidence: 99%