Chlamydia trachomatis is the world’s most prevalent bacterial sexually transmitted infection, with over 130 million new cases reported globally each year. Despite this staggering figure, current treatments remain heavily reliant on broad-spectrum antibiotics such as doxycycline and azithromycin—drugs that not only target harmful thogens but also disrupt beneficial microbiota and contribute to the growing crisis of antibiotic resistance.
In response to this challenge, researchers at Umeå University have made a pioneering breakthrough in developing selective, sustainable treatments specifically targeting Chlamydia. Their innovation centers on the discovery of over 60 novel anti-chlamydial molecules. These compounds are chemically distinct from traditional antibiotics and exhibit high potency against Chlamydia in cell cultures without damaging human cells or beneficial bacteria.
The research team, led by Barbara Sixt, applied both experimental and virtual screening techniques to identify these promising candidates. A key part of their methodology involved using a fluorescent strain of Chlamydia to screen tens of thousands of compounds for anti-bacterial activity while monitoring human cell viability. Of the compounds identified, several demonstrated the ability to eradicate both active and persistent infections in a bactericidal manner.
The most potent of these, referred to as compound c1e, has been shown to covalently bind to and inhibit Chlamydia’s FabH enzyme—an essential component of the bacterium’s fatty acid biosynthesis pathway. This pathway is critical for bacterial growth but is absent in human cells, making it an ideal therapeutic target. Moreover, c1e operates selectively without disrupting the host’s gut or vaginal microbiota, a significant advantage over existing treatments.
Beyond killing the bacteria, some compounds even showed synergistic effects when used with existing antibiotics, suggesting potential for combination therapies that reduce drug resistance and side effects. The compounds also maintained efficacy across different human and animal cell types and Chlamydia strains, including ocular and urogenital variants.
This collaborative project brought together expertise from multiple partners including Umeå University, the Laboratory for Molecular Infection Medicine Sweden (MIMS), and the European Molecular Biology Laboratory (EMBL). Their joint efforts combined advanced molecular biology, chemical screening, and computational modeling to achieve this scientific milestone.
The research was funded by several major organizations, including the Knut and Alice Wallenberg Foundation and the European Research Council. The project also received support from the Swedish Research Council and SciLifeLab. The total cost of the multi-year initiative is estimated to be around 40 million SEK (approximately 3.5 million USD), covering high-throughput screening, compound development, and collaborative research infrastructure.
Importantly, these discoveries were made possible by integrating machine learning models to predict anti-chlamydial activity and streamline the virtual screening of chemical libraries. This not only accelerated the discovery process but opened new possibilities for finding treatments against other hard-to-target intracellular pathogens.
While further development and clinical trials are necessary before these treatments become widely available, the findings represent a critical step toward more effective and responsible antibiotic use. With the growing threat of antimicrobial resistance, such innovations may transform the global approach to sexually transmitted infections, ensuring treatments are both effective and ecologically sustainable.
This groundbreaking research marks a shift toward precision antibiotics—targeted treatments that are powerful against pathogens like Chlamydia while sparing the body’s vital microbial communities.
