MohammedRazavi Momin 12/11/2017 Research C-di-GMP Riboswitch as a possible antibiotic target Background Antibiotic use has dramatically increased over the past serval years, and due to the over use of antibiotic bacteria are becoming more resistant to the drugs. This leads to more and stronger antibiotic use which then leads to further resistance. Today there are many different classes of antibiotic that are being used such as Penicillin’s, Cephalosporins, macrolides, and many more. These various classes effect bacteria in a way which prevent them from multiplying, growing, or infecting host cells. But even though we have so many different antibiotics out there, development and discover of new antibiotic drug that target different components of bacteria are important to combat the increasing number of resistance bacteria. One such possible target is Riboswitch. Method For this research, I search literature to find articles on information about riboswitches specifically cyclic-di-GMP riboswitch. I used PubMed as search base to find the articles. First, I wanted to see what are the different possible antibiotic target out there that do not have any antibiotic developed. To find out, I searched PubMed for possible antibiotic targets which lead to articles on Non-coding RNA as possible antibiotic targets. After reading a few articles on that, I decided to look more in to riboswitch, specifically c-di-GMP riboswitch. Then I went on to find more articles which talked about c-di-GMP riboswitch and how it works, the structure of the riboswitch and ligand binding of the riboswitch. After that I went on to search in what organism was this riboswitch found in, such as in Gram positive or Gram-Negative bacteria and if this riboswitch was present in humans. After doing these search, I compiled different articles for this research. Result Form the literature search a lot of new and different target were identified one of which include Non-coding RNA regions which shows to be a very promising antibiotic target. Within the non-coding region of the RNA, riboswitch seemed the most interesting. Riboswitch effect gene expression by interacting with ligand and changing the RNA conformation which effect downstream gene expression. There are many different types of riboswitch, one of which is the cyclic dimeric guanosine monophosphate (c-di-GMP). C-di-GMP riboswitch regulate different bacterial process including pathogenesis, biofilm formation and motility. C-di-GMP is a second messenger signaling molecule. Not a lot of research has gone in to developing antibiotic that target c-di-gmp, but some ligands have been identified. The structure of the riboswitch has been identified and logged in to the protein data base. There were not many article and research done on which specific bacteria has the c-di-riboswitch, but the article that I did find stated that this riboswitch may be present in gram positive bacteria such as Clostridium difficile, Listeria monocytogenes, Bacillus subtilis, and Streptomyces coelicolor. Currently no research shows that this riboswitch is present in human, but further research needs to be done to fully identify that. A lot of the research done with cdi-GMP is to identify its structure and ligand binding. Discussion With the current article on c-di-GMP riboswitch, it shows that more research needs to be done to fully identify its possible target and how it can play a role in antibiotic target. But if further research is conducted, specifically focused on finding compounds that can affect the riboswitch, this can be a good antibiotic target. Even though this riboswitch is not present in the common bacteria, this riboswitch is a good antibiotic target. An antibiotic developed for this riboswitch can affect the bacteria ability to form biofilm, motility, and pathogenesis. This may also have led to further identification of other possible antibiotic targets that are in the non-coding region which may be involved in more bacteria and possibly prevent resistance. Because of the limited bacteria that has this riboswitch, it can possible be a problem to develop an antibiotic. And because of the limited data on the effect of the riboswitch and its effect on the human body, it can also be a potential problem of that the antibiotic or what the riboswitch can do in the human body. Kulshina N, Baird NJ, Ferré-Damaré AR. Recognition of the bacterial second messenger cyclic diguanylate by its cognate riboswitch. Nature Structural & Molecular Biology. 2009;16(12):1212-1217. doi:10.1038/nsmb.1701. Bakheet TM, Doig AJ. Properties and identification of human protein drug targets. Bioinformatics. 2009;25(4):451-457. doi:10.1093/bioinformatics/btp002. Bakheet TM, Doig AJ. Properties and identification of human protein drug targets. Bioinformatics. 2009;25(4):451-457. doi:10.1093/bioinformatics/btp002. Colameco S, Elliot MA. Non-coding RNAs as antibiotic targets. Biochemical Pharmacology. 2017;133:29-42. doi:10.1016/j.bcp.2016.12.015. Purcell EB, Tamayo R. Cyclic diguanylate signaling in Gram-positive bacteria. FEMS Microbiology Reviews. 2016;40(5):753-773. doi:10.1093/femsre/fuw013. Smith KD, Shanahan CA, Moore EL, Simon AC, Strobel SA. Structural basis of differential ligand recognition by two classes of bis-(3-5)-cyclic dimeric guanosine monophosphate-binding riboswitches. Proceedings of the National Academy of Sciences. 2011;108(19):7757-7762. doi:10.1073/pnas.1018857108. Smith KD, Lipchock SV, Ames TD, Wang J, Breaker RR, Strobel SA. Structural basis of ligand binding by a c-di-GMP riboswitch. Nature Structural & Molecular Biology. 2009;16(12):12181223. doi:10.1038/nsmb.1702.