Evaluation of P-type ATPase Blockers in Mycobacteria bovis BCG
(2021) MOBK01 20211Degree Projects in Molecular Biology
- Popular Abstract
- Effect of zinc-transporter blockers to induce intoxication in Mycobacteria
The World Health Organisation estimated of 10 million new cases of Tuberculosis in 2019 and an annual death rate of 1.4 million. This makes the disease the leading cause of death brought about by one infectious agent, namely Mycobacteria tuberculosis (Mtb). Because of the emergence of multi resistant bacterial strains, substandard vaccines, long treatment periods and difficulties in diagnostic latent infections, the need to develop new, alternative drugs is urgent. The bacteria are spread between hosts via air born aerosol and mostly affect the pulmonary tracts where they are captured by cells of the immune system. In an attempt to rid the host of bacteria, these... (More) - Effect of zinc-transporter blockers to induce intoxication in Mycobacteria
The World Health Organisation estimated of 10 million new cases of Tuberculosis in 2019 and an annual death rate of 1.4 million. This makes the disease the leading cause of death brought about by one infectious agent, namely Mycobacteria tuberculosis (Mtb). Because of the emergence of multi resistant bacterial strains, substandard vaccines, long treatment periods and difficulties in diagnostic latent infections, the need to develop new, alternative drugs is urgent. The bacteria are spread between hosts via air born aerosol and mostly affect the pulmonary tracts where they are captured by cells of the immune system. In an attempt to rid the host of bacteria, these immune cells overload them with zinc ions to induce intoxication. The bacteria, in turn, respond with zinc transportation out of their cells through pumps located in their membrane. Mtb is dependent on these pumps for survival in these elevated levels of zinc, hence, inhibiting activity of such pumps could lead to an induction of metal poisoning and clearance of Mtb.
During this project, the efficiency of seven different inhibitors for such zinc pumps was evaluated. Through monitoring the growth and survival of the Mtb relative Mycobacteria bovis Bacillus Calmette-Guérin (BCG) in the presence of different concentrations of these inhibitors, their respective minimum inhibitory concentration (MIC) was determined. The MIC is defined as the lowest concentration of inhibitor where no BCG growth can be observed. The method for analysis involves a luminous, detectable signal from live BCG which allows for detection of growth. Furthermore, a method based on a detectable colour change was used, where such change implied bacterial survival.
The test yielded rather ineffectual results with high variance of growth inhibition between different replication. The BCG was clearly affected negatively by the presence of the inhibitors and growth decreased during treatment with them all, although to what degree differed markedly during treatment with the same inhibitor. However, complete inhibition was not observed and therefore, the MIC could not be determined. Suggestively, repeated tests may give more reliable results.
To investigate the inhibitors respective suitability as antibiotic agents their toxicity on human cells were examined. By using white blood cells, altered to express a detectable signal in response to inflammation, any inflammation caused by the inhibitors present at different concentrations could be quantified. Additionally, the amount of live blood cells after the same inhibitor treatment was examined. The results from these tests show minimal induction of inflammation during exposure to all inhibitors, cellular death on the other hand, was seen to a greater extent for most inhibitors except compound 7, indicating toxicity for all but one inhibitor. However, the toxicity test needs to be repeated for statistical relevance.
Supervisor: Gabriela Godaly
Co-supervisor: Komal Umashankar Rao
Bachelor thesis, MOBK01, 15 ETC, 2021
Department of Molecular Biology, Lund University (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9060090
- author
- Denison, Linn
- supervisor
- organization
- course
- MOBK01 20211
- year
- 2021
- type
- M2 - Bachelor Degree
- subject
- language
- English
- id
- 9060090
- date added to LUP
- 2021-06-30 16:15:42
- date last changed
- 2021-06-30 16:15:42
@misc{9060090, author = {{Denison, Linn}}, language = {{eng}}, note = {{Student Paper}}, title = {{Evaluation of P-type ATPase Blockers in Mycobacteria bovis BCG}}, year = {{2021}}, }