Comparative genomics and transcriptomics in trachoma

Trachoma is a chronic eye disease that is the leading cause of infectious blindness in the world. It is caused by repeated infection of the under side of the eye lidcalled the conjunctivawith the bacterium Chlamydia trachomatis. Trachoma is a public health problem in 41 countries, and is responsible for the visual impairment of about 2.2 million people. Of an estimated 232 million trachoma cases, Africa is home to over 89% of them. Ethiopia has the highest numbers of active trachoma cases despite years of intervention. The primary intervention that has been deployed in Ethiopia is repeated annual or biannual treatment of children with oral antibiotics as part of the World Health Organizations SAFE program. SAFE stands for Surgery to correct eyelashes that have turned inward, Antibiotics to treat C. trachomatis, Face washing to prevent infection, and Environmental changes such as the installation of latrines to improve overall hygiene. After 15 years of S and A treatment in Ethiopia, a new approach is required to combat trachoma in Africa. The overall objective of this project is to determine the underlying causes of trachoma in Ethiopia. We will identify the diversity of C. trachomatis strains and host- and pathogen-specific responses to C. trachomatis infection that may facilitate infection, reinfection and transmission of the bacteria. Using comparative Whole-Genome Sequencing techniques, we will investigate the genomic diversity of C. trachomatis strains among infected individuals from villages in the trachoma hyperendemic Amhara region of Ethiopia to identify genes and mutations that are critical in enhancing the eye infection and disease among the population. We will also investigate the interactions between the host and C. trachomatis strains from trachoma patients by infecting human cells and analyzing the host and bacterial responses. This will help us to identify pathways that drive infection, reinfection and maintenance of that infection among Ethiopian trachoma patients. We hope to develop novel therapeutic approaches and prevention strategies to decrease/prevent infection, transmission and the devastating sequelae of blindness in Ethiopia and other parts of Africa where trachoma is endemic.

Trachoma, a severe eye infection caused by the bacterium Chlamydia trachomatis (Ct), is the world's leading cause of preventable blindness. This disease, prevalent in many low-resource regions, particularly affects African countries. Our research investigates the genetic diversity and evolution of two primary Ct strains, called serovar A (SvA) and serovar B (SvB), in trachoma-endemic communities in The Gambia and Northern Tanzania. Additionally, we study how these Ct strains interact with host cells using transcriptomics, which helps us understand how human cells respond to infection at the molecular level. In The Gambia, we analyzed genetic differences in Ct strains across villages before mass antibiotic treatments. Our findings reveal that unique genetic changes in SvA and SvB strains may influence the bacterium's ability to survive and spread, suggesting potential adjustments for trachoma control strategies. In Tanzania, we monitored Ct strains over four years before and after community-wide antibiotic treatments. Notably, we observed that the more persistent SvA strain grew in prevalence after these treatments, and unique genetic adaptations in SvA indicate that certain strains may adapt over time to withstand antibiotic pressure. Transcriptomics analysis of host cells showed distinct patterns in response to Ct SvA and SvB infection. Specifically, human conjunctival cells exhibited a heightened expression of inflammation-related genes in response to SvB compared to SvA, suggesting that SvB might trigger a stronger inflammatory response during initial infection. This research provides valuable insights into how Ct strains are evolving within trachoma-endemic populations. The findings on genetic adaptation have the potential to guide more targeted interventions, aiming to reduce trachoma transmission and ultimately prevent blindness on a larger scale. Additionally, the transcriptomics data suggests that different Ct strains may trigger distinct responses during eye infections, highlighting the possibility of developing interventions not only to control transmission but also to mitigate inflammatory damage that leads to blindness. Further studies are essential to enhance our understanding of the interaction of Ct with its host eukaryotic cells and the ways in which Ct may adapt under ongoing antibiotic interventions.