Chlamydia trachomatis Infections | CDC EID

Volume 15, Number 9–September 2009
Research
Predicting Phenotype and Emerging Strains among Chlamydia trachomatis Infections
Deborah Dean, William J. Bruno, Raymond Wan, João P. Gomes, Stéphanie Devignot, Tigist Mehari, Henry J.C. de Vries, Servaas A. Morré, Garry Myers, Timothy D. Read, and Brian G. Spratt
Author affiliations: Children's Hospital Oakland Research Institute, Oakland, California, USA (D. Dean, R. Wan, T. Mehari); University of California, San Francisco, California, USA (D. Dean); University of California, Berkeley, California, USA (D. Dean); Los Alamos National Laboratories, Los Alamos, New Mexico, USA (W.J. Bruno); National Institute of Health, Lisbon, Portugal (J.P. Gomes); Institut de Médecine Tropicale du Service de Santé des Armées, Marseille, France (S. Devignot); University of Amsterdam, the Netherlands (H.J.C. de Vries); Vrije Universiteit Medical Center, Amsterdam (S.A. Morré); University of Maryland School of Medicine, Baltimore, Maryland, USA (G. Myers); Emory University, Atlanta, Georgia, USA (T.D. Read); and Imperial College, London, UK (B.G. Spratt)

Suggested citation for this article

Abstract
Chlamydia trachomatis is a global cause of blinding trachoma and sexually transmitted infections (STIs). We used comparative genomics of the family Chlamydiaceae to select conserved housekeeping genes for C. trachomatis multilocus sequencing, characterizing 19 reference and 68 clinical isolates from 6 continental/subcontinental regions. There were 44 sequence types (ST). Identical STs for STI isolates were recovered from different regions, whereas STs for trachoma isolates were restricted by continent. Twenty-nine of 52 alleles had nonuniform distributions of frequencies across regions (p<0.001). Phylogenetic analysis showed 3 disease clusters: invasive lymphogranuloma venereum strains, globally prevalent noninvasive STI strains (ompA genotypes D/Da, E, and F), and nonprevalent STI strains with a trachoma subcluster. Recombinant strains were observed among STI clusters. Single nucleotide polymorphisms (SNPs) were predictive of disease specificity. Multilocus and SNP typing can now be used to detect diverse and emerging C. trachomatis strains for epidemiologic and evolutionary studies of trachoma and STI populations worldwide.

Chlamydia trachomatis is spread by close social contact or sexual activity. Worldwide, C. trachomatis is the leading preventable cause of blindness and bacterial sexually transmitted infections (STIs). Various typing techniques have been developed to better understand the epidemiology and pathogenesis of chlamydial diseases. Early typing schemes used monoclonal and polyclonal antibodies directed against the major outer membrane (MOMP) (1), and differentiated the organism into serovars and seroclasses: B class (comprising serovars B, Ba, D, Da, E, L2, L2a), C class (A, C, H, I, Ia, J, Ja, K, L1, L3), and intermediate class (F, G). Sequencing of ompA, which encodes MOMP, has refined typing, detecting numerous trachoma (2,3) and sexually transmitted (4,5) serovar subtypes.

Seroclasses, however, do not correlate with disease phenotypes. For example, A, B, Ba, and C are responsible for trachoma, whereas lymphogranuloma venereum (LGV) strains, L1-3, are associated with invasive diseases, such as suppurative lymphadenitis and hemorrhagic proctitis (6). Other typing techniques, such as restriction fragment length polymorphism (7), random amplification of polymorphic DNA, or pulsed-field gel electrophoresis (PFGE) (8), and amplified fragment length polymorphism (AFLP) (9) also correlate poorly with disease phenotype, and none have been standardized across laboratories.

Multilocus sequence typing (MLST) has been used to characterize strains and lineages of numerous pathogens associated with human diseases that cause serious illness and death, including Neisseria meningitidis, Staphylococcus aureus, Vibrio cholerae, and Haemophilus influenzae. MLST uses 500–700 bp sequences of internal regions of 6–8 housekeeping genes, excluding genes suspected to be under immune selection (where there is positive selection for sequence diversity) and ribosomal RNA genes (which are multicopy and too conserved) (10). Advantages of MLST include its precision, allowing simple interlaboratory comparisons, good discrimination between strains, and buffering against the distorting effect of recombination on genetic relatedness. MLST data are also amenable to various population genetic analyses (11,12). Databases for >30 species are curated at www.mlst.net and pubmlst.org. In parallel with our study, 2 multilocus schemes have recently been developed for C. trachomatis. The first violated the above premise by including ompA, which is under immune selection (13). The second included only laboratory-adapted and 5 clinical E strains from the Netherlands (14).

In this work, unlike the other C. trachomatis MLST schemes, we used complete genomic comparisons of 7 strains from 4 species within the family Chlamydiaceae to identify conserved candidate housekeeping genes across the genomes. This approach ensures that the chosen loci are stable over the course of evolution, and allows for future application of a unified MLST scheme for other Chlamydiaceae spp. We typed a diverse worldwide collection of reference and clinical isolates from trachoma and STI populations, correlating genetic variation with geography and disease phenotype. We found disease-specific single nucleotide polymorphisms (SNPs) and a diversity of new strains including recombinant strains that occurred for ompA relative to housekeeping loci, following up on our recent discovery of this phenomenon at multiple loci in Chlamydiaceae genomes (15–17).

Suggested Citation for this Article

Dean D, Bruno WJ, Wan R, Gomes JP, Devignot S, Mehair T, et al. Predicting phenotype and emerging strains among Chlamydia trachomatis infections. Emerg Infect Dis [serial on the internet]. 2009 Sep [date cited]. Available from http://www.cdc.gov/EID/content/15/9/1385.htm

DOI: 10.3201/eid1509.090272

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