A Theoretical Framework for a Non-Antibiotic Approach to Combat Vibrio cholerae Outbreaks in Syrian Refugee Camps in Lebanon

Abstract

Cholera, caused by Vibrio cholerae, remains a significant public health challenge, particularly in vulnerable regions such as Lebanon, where a state of emergency was declared in response to outbreaks in Syrian refugee camps. The lack of access to clean water in these camps has made refugees highly susceptible to V. cholerae infections, which are characterized by gastrointestinal symptoms, including diarrhea and vomiting. In severe cases, infection can lead to rapid dehydration, and if untreated, may result in organ failure and death. Antibiotics, including tetracyclines, fluoroquinolones, and macrolides, are commonly used for severe cholera cases, particularly when resistance is confirmed. However, V. cholerae has developed resistance to these antibiotics through various mechanisms, complicating treatment and increasing the urgency for alternative therapeutic approaches. This theoretical study investigates a cost-effective, non-antibiotic strategy to combat cholera using engineered Lactococcus lactis as a probiotic delivery system. We hypothesize that combining conjugated linoleic acid (CLA) with genetically modified L. lactis could offer an innovative treatment. CLA, a polyunsaturated fatty acid with well-established antimicrobial properties, inhibits V. cholerae growth and toxin production. Additionally, L. lactis is genetically engineered to express the chimeric monoclonal antibody ZAC-3, which has been shown to inhibit V. cholerae motility, preventing it from colonizing the small intestine and causing infection. ZAC-3 is hypothesized to be displayed on the surface of L. lactis using recombinant DNA technology, with a proposed surface-anchoring sequence (AcmA3b) to enable direct interaction with the pathogen. This approach offers a novel, sustainable alternative to antibiotics, with linoleic acid supplementation further enhancing its therapeutic efficacy. Our cost analysis demonstrates that the engineered L. lactis strain, when used as a dietary supplement, is affordable and suitable for integration into food donation programs. Its probiotic nature ensures safety without triggering immune responses. In conclusion, while experimental validation is essential, this theoretical research proposes a dual-action approach using CLA and ZAC-3-engineered L. lactis to address the growing issue of antibiotic resistance in cholera and other bacterial infections, providing a viable solution without the drawbacks associated with traditional antibiotics.