Premium
Localized reversible frameshift mutation in an adhesin gene confers a phase‐variable adherence phenotype in mycoplasma
Author(s) -
Zhang Qijing,
Wise Kim S.
Publication year - 1997
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.1997.mmi509.x
Subject(s) - frameshift mutation , biology , phase variation , genetics , gene , antigenic variation , mutation , tandem repeat , sequence analysis , mollicutes , stop codon , lineage (genetic) , mycoplasma hominis , phenotype , mycoplasma , genome
The variable adherence‐associated (Vaa) antigen of Mycoplasma hominis is an abundant surface lipoprotein adhesin that may mediate important interactions of this wall‐less prokaryotic pathogen with the human host. Extensive mutational variation of Vaa size, as well as sequence and antigenic divergence, has been described previously. Using a series of clonal isolates representing an isogenic lineage of variants oscillating in Vaa expression, Vaa is further shown in this study to undergo high‐frequency phase variation in expression, which correlated precisely with the ability of M . hominis to adhere to cultured human cells. Although no DNA rearrangements or sequence differences in the 5′ regions flanking vaa alleles were detected between Vaa + and Vaa − variants, intragenic vaa sequences from this lineage revealed an oscillating mutation involving a single nucleotide deletion/insertion in a short tract of adenine residues near the 5′ end of the mature Vaa coding sequence, which created a translational frameshift resulting in either a complete Vaa ORF or an in‐frame UAG stop codon immediately downstream of the poly‐A tract. Evidence for the occurrence of this high‐frequency frameshift mutation in vivo was obtained from analysis of PCR‐generated vaa sequences amplified from the joint synovial fluid of a patient with M . hominis ‐associated arthritis, which indicated that Vaa phase variation occurs during M . hominis infection in the natural host. These results identify a distinctive frameshift mutator element in the vaa gene that governs M . hominis adherence and highlight the importance of mutational alteration of primary gene products on the mycoplasma surface as a means of generating and maintaining functional diversity in the host.