Evidence for Reductive Genome Evolution and Lateral Acquisition of Virulence Functions in Two Corynebacterium pseudotuberculosis Strains

Abstract

Background Corynebacterium pseudotuberculosis, a Gram-positive, facultative intracellular pathogen, is the etiologic agent of the disease known as caseous lymphadenitis (CL). CL mainly affects small ruminants, such as goats and sheep; it also causes infections in humans, though rarely. This species is distributed worldwide, but it has the most serious economic impact in Oceania, Africa and South America. Although C. pseudotuberculosis causes major health and productivity problems for livestock, little is known about the molecular basis of its pathogenicity.Methodology and FindingsWe characterized two C. pseudotuberculosis genomes (Cp1002, isolated from goats; and CpC231, isolated from sheep). Analysis of the predicted genomes showed high similarity in genomic architecture, gene content and genetic order. When C. pseudotuberculosis was compared with other Corynebacterium species, it became evident that this pathogenic species has lost numerous genes, resulting in one of the smallest genomes in the genus. Other differences that could be part of the adaptation to pathogenicity include a lower GC content, of about 52%, and a reduced gene repertoire. The C. pseudotuberculosis genome also includes seven putative pathogenicity islands, which contain several classical virulence factors, including genes for fimbrial subunits, adhesion factors, iron uptake and secreted toxins. Additionally, all of the virulence factors in the islands have characteristics that indicate horizontal transfer.ConclusionsThese particular genome characteristics of C. pseudotuberculosis, as well as its acquired virulence factors in pathogenicity islands, provide evidence of its lifestyle and of the pathogenicity pathways used by this pathogen in the infection process. All genomes cited in this study are available in the NCBI Genbank database (http://www.ncbi.nlm.nih.gov/genbank/) under accession numbers CP001809 and CP001829.

Genome Sequence of the Corynebacterium pseudotuberculosis Cp316 Strain, Isolated from the Abscess of a Californian Horse

“…C. pseudotuberculosis is an actinobacterium that belongs to the CMNR group, which includes the genera Corynebacterium, Mycobacterium, Nocardia, and Rhodococcus (6).…”

The Family Corynebacteriaceae

“…The first next-generation DNA sequencing studies have focused on the genomes of corynebacterial pathogens because of their importance in human and animal disease. Complete genome sequences are meanwhile available for a black-pigmented Corynebacterium aurimucosum isolate (Trost et al 2010a), multiple toxigenic and non-toxigenic strains of Corynebacterium diphtheriae (Cerdeño-Tarrága et al 2003;Trost et al 2012), Corynebacterium jeikeium , Corynebacterium kroppenstedtii (Tauch et al 2008a), multiple strains of the Corynebacterium pseudotuberculosis biovars ovis and equi (Trost et al 2010b;Cerdeira et al 2011a, b;Ruiz et al 2011;Silva et al 2011Silva et al , 2012Hassan et al 2012;Lopes et al 2012;Pethick et al 2012a, b;Ramos et al 2012), Corynebacterium resistens (Schröder et al 2012a), Corynebacterium ulcerans from human and animal sources Sekizuka et al 2012), and Corynebacterium urealyticum (Tauch et al 2008b). Complete genome sequences from environmental corynebacteria include Corynebacterium efficiens , Corynebacterium glutamicum (Kalinowski et al 2003;Ikeda and Nakagawa 2003;Yukawa et al 2007), and Corynebacterium variabile .…”

“…The fagABC operon and the fagD gene are involved in iron acquisition and play a supportive role in virulence of Corynebacterium pseudotuberculosis (Billington et al 2002). The fag genes are found on a pathogenicity island along with the pld gene which encodes phospholipase D (Ruiz et al 2011). More recently, the presence of two pilus gene clusters has been reported in the genome of Corynebacterium pseudotuberculosis FRC41 (Trost et al 2010b).…”

PANNOTATOR: an automated tool for annotation of pan-genomes

“…These parameters include the percentage of protein identity and the total extension of the alignment between amino acids. For instance, during the C. pseudotuberculosis pan-genome start (Ruiz et al, 2011), a threshold of 95% amino acid identity and sequence alignment was used, which is sufficient to correctly link most of the CDS among different strains. However, for the first automatic annotation of a C. pseudotuberculosis genome, it was necessary to use the genome of C. diphtheriae (Cerdeño-Tárraga et al, 2003), the phylogenetically closest organism available, and a threshold of 65% protein identity and sequence alignment.…”