The pan-genome of the animal pathogen Corynebacterium pseudotuberculosis reveals differences in genome plasticity between the biovar ovis and equi strains.

Síntia Almeida ,Jochen Blom,Rommel Thiago Jucá Ramos ,Amjad Ali,Maria Paula Cruz Schneider ,Vasco Azevedo,Carlos Diniz,Andreas Tauch,Karina K F Nascimento ,Ulisses De Pádua Pereira ,Eva Trost,Vinícius Augusto Carvalho De Abreu ,Syed Shah Hassan ,Siomar C Soares,Eudes Guilherme Vieria Barbosa ,Luís Carlos Guimarães ,Anne C Pinto,Anderson Santos ,Adriana Ribeiro Carneiro ,Flávia Souza Rocha ,Syeda Marriam Bakhtiar ,Fernanda Alves Dorella ,Flávia Figueira Aburjaile ,Artur M S Silva ,Anderson Miyoshi

doi:10.1371/journal.pone.0053818

Síntia Almeida , Jochen Blom + Show 23 more

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https://doi.org/10.1371/journal.pone.0053818

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Abstract

Corynebacterium pseudotuberculosis is a facultative intracellular pathogen and the causative agent of several infectious and contagious chronic diseases, including caseous lymphadenitis, ulcerative lymphangitis, mastitis, and edematous skin disease, in a broad spectrum of hosts. In addition, Corynebacterium pseudotuberculosis infections pose a rising worldwide economic problem in ruminants. The complete genome sequences of 15 C. pseudotuberculosis strains isolated from different hosts and countries were comparatively analyzed using a pan-genomic strategy. Phylogenomic, pan-genomic, core genomic, and singleton analyses revealed close relationships among pathogenic corynebacteria, the clonal-like behavior of C. pseudotuberculosis and slow increases in the sizes of pan-genomes. According to extrapolations based on the pan-genomes, core genomes and singletons, the C. pseudotuberculosis biovar ovis shows a more clonal-like behavior than the C. pseudotuberculosis biovar equi. Most of the variable genes of the biovar ovis strains were acquired in a block through horizontal gene transfer and are highly conserved, whereas the biovar equi strains contain great variability, both intra- and inter-biovar, in the 16 detected pathogenicity islands (PAIs). With respect to the gene content of the PAIs, the most interesting finding is the high similarity of the pilus genes in the biovar ovis strains compared with the great variability of these genes in the biovar equi strains. Concluding, the polymerization of complete pilus structures in biovar ovis could be responsible for a remarkable ability of these strains to spread throughout host tissues and penetrate cells to live intracellularly, in contrast with the biovar equi, which rarely attacks visceral organs. Intracellularly, the biovar ovis strains are expected to have less contact with other organisms than the biovar equi strains, thereby explaining the significant clonal-like behavior of the biovar ovis strains.

Highlights

The genus Corynebacterium belongs to the CMNR group from the supra-generic group of Actinomycetes, which includes genera of great medical, veterinary, and biotechnological importance, such as Corynebacterium, Mycobacterium, Nocardia, and Rhodococcus
The genus is composed of pathogenic species such as Corynebacterium diphtheriae, the causative agent of diphtheria [4]; opportunistic pathogens such as Corynebacterium jeikeium, which is responsible for some nosocomial infections in humans [5]; and non-pathogenic species such as Corynebacterium glutamicum, which is highly utilized in industrial amino acid production [6]
Genome Sequences The genome sequences of 15 C. pseudotuberculosis strains were retrieved from the NCBI database: 9 biovar ovis strains, which were isolated from sheep, goats, humans, llamas, antelopes, and cows, and 6 biovar equi strains, which were isolated from horses, camels, and buffalo (Table 1)

Summary

Introduction

The genus Corynebacterium belongs to the CMNR group from the supra-generic group of Actinomycetes, which includes genera of great medical, veterinary, and biotechnological importance, such as Corynebacterium, Mycobacterium, Nocardia, and Rhodococcus. These genera have specific features in common, such as a high DNA G+C content and a specific organization of the cell wall, which is mainly composed of peptidoglycans, arabinogalactans, and mycolic acids [1]. Corynebacterium pseudotuberculosis is a facultative intracellular and pleomorphic member of the genus Corynebacterium This bacterium is non-motile, it does possess fimbriae, and it is the causative agent of caseous lymphadenitis (CLA) in sheep and goats [7]. The initial classification of C. pseudotuberculosis was based on morphological and biochemical characteristics [7,11]: the results of the nitrate reduction test play an important role in distinguishing the biovar ovis (isolated from sheep and goats; negative nitrate reduction) from the biovar equi (isolated from horses and bovines; positive nitrate reduction) [12]

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