Identification of a New Variable Sequence in the P1 Cytadhesin Gene of Mycoplasma pneumoniae : Evidence for the Generation of Antigenic Variation by DNA Recombination between Repetitive Sequences

Abstract

A Mycoplasma pneumoniae cytadhesin P1 gene with novel nucleotide sequence variation has been identified. Four clinical strains of M. pneumoniae were found to carry this type of P1 gene. This new P1 gene is similar to the known group II P1 genes but possesses novel sequence variation of approximately 300 bp in the RepMP2/3 region. The position of the new variable region is distant from the previously reported variable regions known to differ between group I and II P1 genes. Two sequences closely homologous to this new variable region were found within the repetitive sequences outside the P1 gene of the M. pneumoniae M129 genome. This suggests that the new P1 gene was generated by DNA recombination between repetitive sequences and the P1 gene locus. The finding of this new type of P1 gene supports the hypothesis that the repetitive sequences of the M. pneumoniae genome serve as a reservoir to generate antigenic variation of the cytadhesin P1 gene.

Genotyping and macrolide resistance of Mycoplasma pneumoniae identified in children with community-acquired pneumonia in Medellín, Colombia

“…Since the first description in 1999 (Kenri et al, 1999), variants of type 2 have been reported in different regions. It is believed that variants are generated by homologous recombination between repetitive regions of the p1 gene and similar regions that are distributed across the bacterial genome (Kenri et al, 1999;Zhao et al, 2011).…”

“…Since the first description in 1999 (Kenri et al, 1999), variants of type 2 have been reported in different regions. It is believed that variants are generated by homologous recombination between repetitive regions of the p1 gene and similar regions that are distributed across the bacterial genome (Kenri et al, 1999;Zhao et al, 2011). The present results differ from those obtained by Martínez et al in Chile, who observed the circulation of type 1 (78.3%) and type 2 (21.7%) strains of M. pneumoniae, and a small proportion (7.1%) of variants of type 2 during the 1-year study period (Martínez et al, 2010).…”

“…At the same time, these regions are recombined with similar regions outside the p1 gene, thereby generating the V1, V2a, V2b, V2c, and V2d variants. It is possible that changes in the p1 gene are associated with antigenic variation of the cellular surface of M. pneumoniae, which can favor evasion from the immune response and generate cyclic pattern in the infections, as well as triggering outbreaks (Razin et al, 1998;Kenri et al, 1999).…”

Epidemiology, clinical manifestations, pathogenesis and laboratory detection ofMycoplasma pneumoniaeinfections: Figure 1

“…The two subtypes of M. pneumoniae most frequently isolated from clinical specimens differ to some extent in the amino acid and nucleotide sequences of P1 and its coding gene (Su et al, 1990), though numerous further variants have been identified in recent years (Kenri et al, 1999;Dorigo-Zetsma et al, 2000Dumke et al, 2004;Pereyre et al, 2007). Although it has not been demonstrated experimentally, the source of these variant sequences is likely to be degenerate repeats of regions of the P1-coding gene present throughout the M. pneumoniae genome (Kenri et al, 1999); recent evidence in the related organism Mycoplasma genitalium supports a model in which these regions interchange with complementary regions, generating diversity in the P1 sequence (Iverson-Cabral et al, 2007;Ma et al, 2007). A recent report from Japan (Kenri et al, 2008) analyzed clinical isolates of M. pneumoniae collected over a several year period to characterize the P1 gene DNA and determined that the prevalent subtype of M. pneumoniae between 1995 and 2001 was group II but that group I strains became more prevalent between 2002 and 2005.…”

Genesis, effects and fates of repeats in prokaryotic genomes

“…For example, in the closely related Mycoplasma pneumoniae and M. genitalium genomes, many parts of the gene coding for the major adhesin, P1 in the former and MgPa in the latter, are repeated (Peterson et al, 1995;Himmelreich et al, 1996). Recombination between these repeats leads to the generation of new variants of the adhesins (Kenri et al, 1999;Iverson-Cabral et al, 2006, 2007. Although initial reports suggested that this variation was linked to antigen variation, the analysis of genome data in the light of experimental analysis of patients' antibodies and the low rate of sequence variation suggests that the variations proceeds for other reasons, for example to vary niche tropism (Rocha & Blanchard, 2002).…”