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Investigation of immune response and toxicity of novel anti-tuberculosis compounds in primary cells

Gradjan, Lejla (2019) MOBK01 20191
Degree Projects in Molecular Biology
Popular Abstract
Does the host derived peptide really effect the silent killer?

Tuberculosis (TB) is one of the leading infectious cause of death in the world via the manipulative agent Mycobacterium tuberculosis. Despite the decrease in deaths over the following years and available drug treatments, the dieses still rank the top of the list and remains a global pandemic. Constant rise of resistant M. tuberculosis strains has increased an enormous concern of this disease. Current TB drugs have low cure rate for these drug resistant bacteria, high mortality and long list of side effects. A pursuit to find new alternative treatments and novel drugs for all forms of M. tuberculosis have become a massive trend in recent years.

The rising potential and... (More)
Does the host derived peptide really effect the silent killer?

Tuberculosis (TB) is one of the leading infectious cause of death in the world via the manipulative agent Mycobacterium tuberculosis. Despite the decrease in deaths over the following years and available drug treatments, the dieses still rank the top of the list and remains a global pandemic. Constant rise of resistant M. tuberculosis strains has increased an enormous concern of this disease. Current TB drugs have low cure rate for these drug resistant bacteria, high mortality and long list of side effects. A pursuit to find new alternative treatments and novel drugs for all forms of M. tuberculosis have become a massive trend in recent years.

The rising potential and alternative candidate for TB treatments are antimicrobial peptides also called host defense peptides (HDPs). They are short proteins produced by all multicellular living species and are part of the immune system. Earlier studies have shown that such peptides can interact with immune responses and modify the functions and responses in the immune system. The effects can either be positive or negative. One such peptide is the confidential host
defense peptide C.

Peptide C has never been tested on TB infected cells before, so the effects of the peptide are unknown. For this reason, human derived cells were infected with Mycobacterium bovis bacilli Calmette-Guerin (BCG) in presence of the host defense peptide C in different concentrations. The activation and protein production of a specific protein (pERK 1/2) known to regulate different functions for cell survival were quantified and compared with uninfected human cells and BCG infected cells without the peptide. Effects of the peptide C, such as downregulatory or up regulatory were evaluated and studied. The stimulation with peptide C upon a BCG infection was conducted either immediately or 3 hours post infection. A technique called western blot was used to detect and study the proteins followed by a quantification protein analyze.

The results obtained indicated an increase in pERK 1/2 when the peptide was added 3 hours post BCG infection and a decrease in pERK 1/2 when peptide C were added immediately. When the peptide was added at a higher concentration the results indicate a decrease in pERK 1/2 post 3h of infection. No conclusion could be made from the obtained results and the effect of peptide C upon BCG infections cannot be determined. It is possible that the peptide has an effect on tuberculosis infections, or it might not. With future studies ahead the functions and effects will be determined.

A toxicity study was also conducted where the toxicity effect of four different confidential compounds intended as potential future TB treatment on human cells were studied. The combination interaction between a potential antimicrobial peptide NZX and two new TB drugs delamanid and bedaquiline were evaluated. Both experiments were conducted by a colorimetric method, where a color change is observed and analyzed.

The results obtained from the toxicity study, indicated high levels of cell death for all compound except compound S3. Thus, indicating that all compound except for S3 are toxic. More studies need to be done to significantly determine the toxicity. Results obtained from the combination interaction were inconclusive and the type of interaction could not be determined. This project shed light for future potential TB studies.

Bachelor’s degree thesis in Molecular Biology 15 hp, 2019
Department of Biology, Lund University

Supervisor: Gabriela Godaly, Senior lecturer
Department of Microbiology, Immunology and Glycobiology, Institution of Laboratory Medicine, Lund University (Less)
Please use this url to cite or link to this publication:
author
Gradjan, Lejla
supervisor
organization
course
MOBK01 20191
year
type
M2 - Bachelor Degree
subject
language
English
id
8990487
date added to LUP
2019-07-09 15:50:31
date last changed
2019-07-09 15:50:31
@misc{8990487,
  author       = {{Gradjan, Lejla}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Investigation of immune response and toxicity of novel anti-tuberculosis compounds in primary cells}},
  year         = {{2019}},
}