Team:UI-Indonesia

Mission: Attacking Cholerae

Vibrio cholerae (Cholera) is a major cause of infant’s death in many tropical countries; however, this disease is often neglected because its symptom closely resembled diarrhea, exept for its mortality rate. Cholera infected a billion people worldwide annualy and significantly increased during post-disaster, especially in rural place with bad sanitation. Similar with the other bacteria, V. cholerae is able to form biofilm and infecting people through its pathogenicity. During high cell density, V. cholerae are hidden inside biofilm to protect them from mileu exterior disturbance; therefore, antibiotic and other drugs treatment became hundreds time less effective against them. Here, we propose a novel strategy to hunt and degrade cholera biofilm by using principles of synthetic biology. Our team genetically enginereed E. coli, an indigenous gut flora, to specifically detect quorum sensing (QS) molecule from V. cholerae. The mutagenic E. coli is able to detect quorum sensing molecule by expressing CqsS histidine-kinases receptor which is naturally expressed in transmembrane domain of V. cholerae. This receptor will sense Cholerae Autoinducer-1 (CAI-1) which is secreted continously and used as a specific interspecies communication signal. CAI-1 molecule act as “find me signal” for mutagenic E.coli when QS molecule binds CqsS receptor and activates motility gene, CheZ, which will enable the E. coli to migrate into the source of infection. It will also activate the killing gene which enables E.coli to produce biofilm enzyme degrading matrix such as: α-amylase, substilisin, and nuclease. After that, our E. coli will secrete peptide 1018, a novel antibiotic peptide indigenous to innate immunity peptide from human cathelicidin, killing V. cholerae. By interconecting the principles of pathogen-directed motility with the dual system degrading and killing biofilm, we significantly develop a novel curative approach or even possibility of short term post-disaster vaccine, by connecting it with slow time based safety module.