Multiple Chlamydiaceae Species in Trachoma: Implications for Disease Pathogenesis and Control

Abstract

Background Chlamydia trachomatis is a unique obligate intracellular bacterium that remains the leading cause of sexually transmitted bacterial diseases and preventable blindness worldwide. Chronic ocular infections are referred to as trachoma, and predominate in developing countries. Since 2001, the World Health Organization has promoted control strategies including antibiotics, improved hygiene, and environmental measures with limited success. Consequently, a vaccine is urgently needed. Integral to vaccine design is an understanding of the interactions of the pathogen and host immune response. Various animal models of trachoma show that urogenital C. trachomatis strains and other species of the family Chlamydiaceae produce severe conjunctival inflammation and scarring similar to that of the ocular C. trachomatis strains. However, we do not know the extent of organisms that may be involved in human trachoma. Furthermore, C. trachomatis heat shock protein 60 (Hsp60) has been implicated in inflammation and conjunctival scarring but the role of other Chlamydiaceae Hsp60 in disease pathogenesis has not been examined. In this study, we set out to identify whether other Chlamydiaceae species are present in trachoma, and determine their association with severity of clinical disease and with mucosal and systemic immune responses to Chlamydiaceae species-specific Hsp60 to further investigate the immunopathogenesis of this blinding disease.Methods and FindingsWe randomly selected nine of 49 households in a trachoma-endemic region of Nepal. Trachoma was graded, and real-time, quantitative (k)PCR was used to detect genomic DNA and cDNA (from RNA) for Chlamydiaceae ompA and 16S rRNA genes, respectively, from conjunctival swabs. IgG antibody responses to recombinant (r) Chlamydiaceae species-specific Hsp60 were determined for tears and sera. Surprisingly, all three species—C. trachomatis, Chlamydophila psittaci, and Chlamydophila pneumoniae—were detected in eight (89%) study households; one household had no members infected with C. pneumoniae. Of 80 (63%; n = 127) infected individuals, 28 (35%) had infection with C. psittaci, or C. pneumoniae, or both; single and dual infections with C. psittaci and C. pneumoniae were significantly associated with severe conjunctival inflammation (OR 4.25 [95% confidence interval (CI), 2.9–11.3], p = 0.009] as were single infections with C. trachomatis (OR 5.7 [95% CI, 3.8–10.1], p = 0.002). Of the 80 infected individuals, 75 (93.8%) were also positive for 16S rRNA by kPCR for the same organism identified by ompA. Individuals with tear IgG immunoreactivity to Chlamydiaceae rHsp60 were eight times more likely than individuals without tear immunoreactivity to be infected (95% CI 6.4–15.1; p = 0.003), 6.2 times more likely to have severe inflammation (95% CI 4.4–12.6; p = 0.001), and 5.7 times more likely to have scarring (95% CI 3.9–11.1; p = 0.019) while individuals with serum IgG immunoreactivity were 4.1 times more likely to be infected (95% CI 3.1–10.1; p = 0.014).ConclusionsWe provide subst...

Emancipating Chlamydia: Advances in the Genetic Manipulation of a Recalcitrant Intracellular Pathogen

“…The evidence for DNA exchange inferred from comparative genomic studies correlates well with reports of mixed chlamydial infections. For instance, in addition to ocular strains found in patients with trachoma, urogenital strains have also been observed in single or mixed infections of the conjunctiva (129). Mixed infections are also prevalent in populations with a high propensity for acquiring STDs (108,111,(130)(131)(132)(133).…”

Structure and Protein-Protein Interaction Studies on Chlamydia trachomatis Protein CT670 (YscO Homolog)

“…They are highly pathogenic and cause genital tract, ocular, and respiratory infections in humans (9,55). A key characteristic of Chlamydiae is their biphasic developmental cycle, in which the bacteria alternate between two morphologies: the elementary body and the reticulate body (1,31).…”

Effect of oral azithromycin in the treatment of chlamydial conjunctivitis

“…It is possible that some of our patients who needed augmented treatments might be due to non-trachomatis Chlamydia infection, as non-trachomatis chlamydial conjunctivitis is thought more common than previously understood, and a longer course of antibiotic treatment than C. trachomatis infection was considered necessary to eradicate the organism. 25,26 In this study, we also observed that older patients had a tendency to require more augmented treatments, but the number of patients was too small to draw a definite conclusion. Further well-powered clinical studies with a larger number of participants are required to confirm this association.…”