Research Paper

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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.
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Colameco S, Elliot MA. Non-coding RNAs as antibiotic targets. Biochemical Pharmacology.
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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.
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