Download Streptomycin Poster

“Soil Science”: Streptomycin and the Treatment
of Tuberculosis (TB)
Gabriela Farfan, Samuel Huang, Susan Huang, Joy Li, JunYao Song,
Peter Vander Velden, Connie Wang, Mary Zhang
Madison West High School, Madison, WI 53726
Advisor: Basudeb Bhattacharyya, University of Wisconsin, Madison, WI 53706
Mentor: Dr. Dave Nelson, University of Wisconsin, Madison, WI 53706
Bacterial Protein Translation
Introduction
Tuberculosis is a disease caused by the
bacterium Mycobacterium tuberculosis
that spreads through air and attacks the
lungs. Prior to 1943, tuberculosis left
untreated had a high mortality rate in the
United States. Streptomycin, an antibiotic,
the first cure found for tuberculosis, was
isolated from the soil organism
Streptomyces griseus in 1943.
We are using rapid prototyping technology
to model the interaction between
streptomycin and the 30S bacterial
ribosomal subunit of RNA. This antibiotic
binds tightly to bacterial 16S rRNA,
causing protein translation to be “error–
prone”. As a result many defective
proteins are synthesized, and the cell dies.
This process does not affect human
ribosomes because human ribosomes do
not have the 16S rRNA. By modeling the
mechanisms of this antibiotic, we hope to
further understand the general
mechanisms of bacterial infection and
antibiotic treatment as well as antibiotic
resistance.
Tuberculosis
affecting the lungs
This process continues until
a complete protein is
synthesized.
Streptomycin: Structure
and Function
Streptomycin affects
the A site
www.bioscience.utah.edu
What is Tuberculosis?
Tuberculosis (TB) is an infectious disease caused by
the bacterium Mycobacterium tuberculosis. It
commonly attacks the lungs, but it can also affect other
parts of the body such as the nervous system or the
circulatory system. Approximately one-third of the the
world population is infected with M. tuberculosis, but
they have a latent form of the disease that only has a
10% chance of developing into active TB. The TB
bacterium is spread through inhaling infected aerosol
droplets when infected persons cough or sneeze. Once
it has entered the lungs, M. tuberculosis invades and
replicates within alveolar macrophages. Lesions occur
at the Ghon focus, typically between lobes in the
lung. From the lungs, the bacillus can spread to other
parts of the body through the bloodstream although
it rarely affects those other parts. When a person gets
an active TB infection, they do not feel well and cough
up mucus or blood among other symptoms. Left
untreated, TB has a 50% mortality rate.
www.alanwood.net
Streptomycin affects the ribosome by binding
the A site where tRNA usually binds. Shown
above, is an anticodon, tRNA (1), and
streptomycin (2). Notice the structural
similarities between streptomycin and the
anticodon that allow streptomycin to fit into the
http://student.ccbcmd.edu/courses/bio141/lecguide/unit2/control/imag
binding site for anticodons and disrupt
es/agmiscode01_illus.jpg
translation.
Supported by the National Institutes of Health (NIH) – National Center for Research Resources Science Education Partnership Award (NCRR-SEPA)
Nelson, D. and Cox, M. (2003)
Lehninger Principles of
Biochemistry, Freeman Publishers,
New York
tRNA-AAs bind to anticodons in the
peptide (P) and acceptor (A) sites.
Peptides are transferred from the tRNA
in the P-site to the tRNA-AA in the Asite.
A new tRNA-AA enters the A site and
the old original tRNA exits the E-site
Streptomycin changes the conformation
of the A-site of the ribosome. This
causes the ribosome to be “error-prone,”
leading to the synthesis of defective
proteins. This leads to cell death.
These pictures show TB lesions in the lung. As shown
in (1), these lesions typically occur between lobes at
the Ghon focus. TB is shown in an advanced stage in
(2).
http://gallery.unl.edu/images/75-sw/75-sw-88.gif
http://www.med.yale.edu/intmed/cardio/imaging/cases/tuberculosis_hilar_ad/graphics/rad1.
gif
Conclusions
•Streptomycin kills bacteria by compromising the
ribosome.
•Streptomycin is an effective antibiotic because its
structure is similar to that of the anticodons that would
usually bind to the ribosome.
•Streptomycin is significant because it was the first
antibiotic that could treat tuberculosis.
•Over time, bacteria have become resistant to
streptomycin.
•By studying the structure of streptomycin, new
antibiotics can be developed to combat diseases such
as TB.