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Updated: Jun 27, 2025
Antibiotic Dereplication Using the Antibiotic Resistance Platform
Published on: October 17, 2019
A large screen identifies beta-lactam antibiotics which can be repurposed to target the syphilis agent
Kathryn A Hayes1,2, Jules M Dressler2,3, Steven J Norris4,5
1Translational Biology, Medicine, and Health, Virginia Tech, Blacksburg, VA 24061 USA.
Abstract:
Syphilis, caused by the spirochete Treponema pallidum subsp. pallidum (hereafter called T. pallidum), is re-emerging as a worldwide sexually transmitted infection. A single intramuscular dose of benzathine penicillin G is the preferred syphilis treatment option. Both supply shortage concerns and the potential for acquired antibiotic resistance further the need to broaden the repertoire of syphilis therapeutics. We reasoned that other β-lactams may be equally or more effective at targeting the disease-causing agent, Treponema pallidum, but have yet to be discovered due to a previous lack of a continuous in vitro culture system. Recent technical advances with respect to in vitro T. pallidum propagation allowed us to conduct a high-throughput screen of almost 100 β-lactams. Using several molecular and cellular approaches that we developed or adapted, we identified and confirmed the efficacy of several β-lactams that were similar to or outperformed the current standard, benzathine penicillin G. These options are either currently used to treat bacterial infections or are synthetic derivatives of naturally occurring compounds. Our studies not only identified additional potential therapeutics in the resolution of syphilis, but provide techniques to study the complex biology of T. pallidum-a spirochete that has plagued human health for centuries.
Insights
New research identifies effective alternative treatments for syphilis, a re-emerging sexually transmitted infection. Several beta-lactam antibiotics show promise, potentially overcoming penicillin shortages and resistance issues.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Syphilis, caused by *Treponema pallidum*, is a growing global health concern.
- Benzathine penicillin G is the standard treatment, but supply issues and antibiotic resistance necessitate new therapeutic options.
- The lack of a continuous in vitro culture system previously hindered the discovery of alternative treatments.
Purpose of the Study:
- To identify novel therapeutic agents for syphilis by screening beta-lactam antibiotics.
- To evaluate the efficacy of these agents against *Treponema pallidum* in vitro.
- To develop and adapt methods for studying *T. pallidum* biology.
Main Methods:
- High-throughput screening of nearly 100 beta-lactam compounds using an established in vitro *T. pallidum* culture system.
- Employing molecular and cellular assays to confirm the efficacy of identified compounds.
- Comparison of novel agents against benzathine penicillin G.
Main Results:
- Several beta-lactam antibiotics demonstrated efficacy against *T. pallidum* in vitro.
- Some identified beta-lactams were as effective or more effective than benzathine penicillin G.
- The screened compounds include existing antibiotics and novel synthetic derivatives.
Conclusions:
- This study identified promising alternative therapeutics for syphilis treatment.
- The findings offer potential solutions to address penicillin shortages and antibiotic resistance in syphilis management.
- The developed techniques advance the study of *Treponema pallidum* biology, aiding future research.
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