Sequence variation and immunogenicity of the Mycoplasma genitalium MgpB and MgpC adherence proteins during persistent infection of men with non-gonococcal urethritis

• Published in: PloS one Vol. 15; no. 10; p. e0240626
• Main Authors: Wood, Gwendolyn E, Iverson-Cabral, Stefanie L, Gillespie, Catherine W, Lowens, M Sylvan, Manhart, Lisa E, Totten, Patricia A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.10.2020; Public Library of Science (PLoS)
• Subjects: Adhesins, Bacterial - genetics; Amino acid sequence; Amino Acid Sequence - genetics; Amino acids; Animals; Antibiotics; Antibodies; Antibodies, Anti-Idiotypic - blood; Antibodies, Anti-Idiotypic - immunology; Antigenic determinants; Antigens; B-Lymphocytes - immunology; B-Lymphocytes - microbiology; Bacterial proteins; Biology and Life Sciences; Chlorocebus aethiops; Chronic infection; Conserved sequence; Crystal structure; Deoxyribonucleic acid; Development and progression; Diagnosis; DNA; Doxycycline - pharmacology; Epitopes; Evolution; Evolution, Molecular; Genetic aspects; Genital tract; Health aspects; Humans; Immune response; Immunodominance; Immunogenicity; Infections; Infectious diseases; Medical research; Medicine and Health Sciences; Men's health; Mycoplasma genitalium; Mycoplasma genitalium - genetics; Mycoplasma genitalium - immunology; Mycoplasma genitalium - pathogenicity; Mycoplasma Infections - blood; Mycoplasma Infections - genetics; Mycoplasma Infections - immunology; Mycoplasma Infections - microbiology; Non-specific urethritis; Nongonococcal urethritis; Patients; Physiological aspects; Polymerase Chain Reaction; Proteins; Public health; Research and Analysis Methods; Structure; Urethritis; Urethritis - blood; Urethritis - genetics; Urethritis - immunology; Urethritis - microbiology; Urine; Variable region; Variation; Vero Cells; Womens health; United States; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0240626

Mycoplasma genitalium is a sexually transmitted bacterial pathogen that infects men and women. Antigenic variation of MgpB and MgpC, the immunodominant adherence proteins of M. genitalium, is thought to contribute to immune evasion and chronic infection. We investigated the evolution of mgpB and mgpC sequences in men with non-gonococcal urethritis persistently infected with M. genitalium, including two men with anti-M. genitalium antibodies at enrollment and two that developed antibodies during follow-up. Each of the four patients was persistently infected with a different strain type and each patient produced antibodies targeting MgpB and MgpC. Amino acid sequence evolution in the variable regions of MgpB and MgpC occurred in all four patients with changes observed in single and multiple variable regions over time. Using the available crystal structure of MgpC of the G37 type strain we found that predicted conformational B cell epitopes localize predominantly to the variable region of MgpC, amino acids that changed during patient infection lie in these epitopes, and variant amino acids are in close proximity to the conserved sialic acid binding pocket. These findings support the hypothesis that sequence variation functions to avoid specific antibodies thereby contributing to persistence in the genital tract.