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Analysis of Novel anti-mycobacterial compounds to treat Tuberculosis

Davids, Camilla Joyce (2021) MOBN03 20202
Degree Projects in Molecular Biology
Popular Abstract
Novel anti-mycobacterial peptides to treat Tuberculosis

Tuberculosis (TB) remains a major health concern since the 19th century. The widespread emergence of anti-microbial resistance to first- line-TB drugs has caused enormous devastation globally as millions of people suffer from the infectious disease. As a result of drug resistance, the treatment plan is extremely long and can take up to two years to successfully clear up the Tuberculosis infection. Undergoing such an extensive treatment plan can be toxic to the body. Thus, various efforts have been made to investigate new TB treatment that require a shorter time-plan to clear up the infection and is biocompatible with human cells.

The research industry is growing extensively to... (More)
Novel anti-mycobacterial peptides to treat Tuberculosis

Tuberculosis (TB) remains a major health concern since the 19th century. The widespread emergence of anti-microbial resistance to first- line-TB drugs has caused enormous devastation globally as millions of people suffer from the infectious disease. As a result of drug resistance, the treatment plan is extremely long and can take up to two years to successfully clear up the Tuberculosis infection. Undergoing such an extensive treatment plan can be toxic to the body. Thus, various efforts have been made to investigate new TB treatment that require a shorter time-plan to clear up the infection and is biocompatible with human cells.

The research industry is growing extensively to develop antimicrobial peptides (AMP) to treat microbes including drug-resistant bacteria. AMPs provide first-line protection against bacteria, fungi and viruses. The Aim of the study is to firstly determine whether the AMPs-CIOP1220 and AP114 are effective in clearing Mycobacterial strains and other gram-positive bacteria. Secondly, to compare the AMPs to other first-and-second- line-TB drugs and to determine which is more effective in clearing up infection. Thirdly, analysing the toxicity of AP114 to human macrophages.

To determine the Minimum Inhibitory concentration (MIC) of AP114 and CIOP1220, the resazurin method was implemented. Briefly, M. tuberculosis spp was incubated with various concentrations of AP114 and CIOP1220 in a 96-well plate. Prestoblue was used an indicator in which a blue colour indicated microbial death and pink indicated microbial growth. To determine the interaction between AP114 and currently used TB drugs, the checkerboard assay was implemented using resazurin and MTT. The checkerboard assay uses the fractional inhibitory index (FIC) to determine whether the combination treatment is either synergistic, additive, indifferent or antagonistic. To calculate the FIC index, the MICs of individual drugs and combination treatment were used. To measure the biocompatibility of human cells with the AP114 peptide, primary macrophages which were obtained from whole blood were incubated with AP114 and analysed using the MTT and ATPlite assays.

CIOP1220 had varying inhibitory activity on gram-positive bacteria but had no activity on Mycobacterium spp. AP114 successfully kills Mycobacterial strains and other gram-positive bacteria in vitro. Additionally, The MIC of AP114 used to inhibit BCG was significantly lower than commonly used TB drugs. Combination treatment of AP114 and specific TB drugs cleared up BCG infection at a significantly lower concentration than using these drugs individually. Toxicology experiments revealed that AP114 appears to be toxic to human macrophages, however, the results were pre-liminary and must be repeated in the future.

AP114 has the potential to have a broad range of anti-microbial activity using extremely low concentrations. The AMP also has promising synergistic and additive interactions with currently used TB drugs, making AP114 a promising future TB treatment option.

Master’s degree project in Molecular Biology, 60 Credits 2021.
Department of Biology-Lund University

Advisors: Gabriela Godaly, Komal Umashankar-Rao.
Tuberculosis research group- BMC B13 (Less)
Please use this url to cite or link to this publication:
author
Davids, Camilla Joyce
supervisor
organization
course
MOBN03 20202
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9058125
date added to LUP
2021-06-23 10:08:15
date last changed
2021-06-23 10:08:15
@misc{9058125,
  author       = {{Davids, Camilla Joyce}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Analysis of Novel anti-mycobacterial compounds to treat Tuberculosis}},
  year         = {{2021}},
}