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

Abstract

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...

Rapid Identification and Differentiation of Mycobacterium avium Subspecies paratuberculosis Types by Use of Real-Time PCR and High-Resolution Melt Analysis of the MAP1506 Locus

“…The lack of extra clusters would indicate that apart from the specific SNPs, the target sequence is conserved. Regarding the three MAC reference strains tested, the preliminary results obtained with HRM analysis were in agreement with former in silico comparison of the MAP1506 sequences in M. avium subspecies avium and M. avium subspecies hominissuis (12). Accordingly, HRM analysis distinguished only M. avium subspecies paratuberculosis types II and III from a cluster containing the MAC strains and M. avium subspecies paratuberculosis type I isolates (see Fig.…”

“…One of the members of this family, MACPPE23 (MAP1506) contains M. avium subspecies paratuberculosis type-specific SNPs in its sequence (12). Previously, these SNPs were used as a target to type M. avium subspecies paratuberculosis isolates by DGGE (10).…”

A 16kb naturally occurring genomic deletion including mce and PPE genes in Mycobacterium avium subspecies paratuberculosis isolates from goats with Johne's disease

“…PE/PPE genes are less abundant in MAP than other mycobacterial species but are thought to influence antigenic diversity, virulence, host adaptation and growth in macrophages (Mackenzie et al, 2009). Zhu et al (2008) reported significant up-regulation of MAP PE4 (MAP1507) and PE (MAP1003c) genes post infection into bovine monocytes.…”

Seroprevalence of Mycobacterium avium Complex in Wild Mammals in the Iberian Peninsula

“…T he members of Mycobacterium spp., comprising the Mycobacterium avium complex (MAC) consist a very interesting group in terms of ecology, differing in virulence and ecology and are the most frequently isolated nontuberculous mycobacteria (Mackenzie et al, 2009). The MAC comprises slow-growing mycobacteria that are ubiquitous in the environment (soil and water) and have a wide source range, causing disease in various mammals and birds (Mackenzie et al, 2009).…”

“…The MAC comprises slow-growing mycobacteria that are ubiquitous in the environment (soil and water) and have a wide source range, causing disease in various mammals and birds (Mackenzie et al, 2009).…”