Postal address P.O. box 2040 3000 CA Rotterdam, NL
Street address Dr. Molewaterplein 40 3015 GD Rotterdam, NL
Accessible by taking tram 8, bus 44 or the Caland line metro (Dijkzigt stop).
Medical Microbiology & Infectious Diseases
www.erasmusmc.nl
To Prirodovedecka fakulta UK, Studijni odbor,
Albertov 6, 128 00 Praha 2 Czech Republic
Fax number: 00 31 10 7033875 Room number: Na-911
Email : j.vanhellemond@erasmusmc.nl
Date: February 28th, 2023
Subject: Report on PhD thesis Katerina Zeniskova
Dear Sir/Madam,
Please find below my written review of the PhD thesis of Katerina Zeniskova entitled
“Effect of various stress factors on mitochondrial processes of pathogenic protists”.
Overall assessment of the thesis
The thesis by Katerina Zeniskova describes original research that is of high quality and of scientific significance. This is reflected by the 3 already published manuscript in peer reviewed scientific journals with a high impact. In addition, the introduction and discussion section of the thesis show that the PhD-candidate can place her research in proper perspective to the current scientific literature. Thereby the thesis fulfils the requirements of the Faculty of Science, Charles University in Prague.
Critical comments
The thesis is clearly written and all research chapters have been published in high quality scientific journals. Hence, these manuscripts have been peer reviewed by experts in the field, which ensures a sound methodology, clear presentation of the results and proper interpretation. Hence, I only have some minor comments on the introduction and discussion section.
- Page 24, figure of N. gruberi metabolism does not include fatty acid metabolism although the last sentence above the graph states that the amoeba has a preference for fatty acids as the main substrate over glucose.
- N. gruberi and N. fowleri are two very closely related amoeba species, and therefore, it surprising that the cellular response of those organisms to two copper chelators (BCS and Neo) is different. Could this be explained by a difference in uptake of Neo by these organisms? Has similar uptake been checked?
General questions
The results of this thesis resulted in new insights, e.g. the different responses to iron or copper limitations between various Naegleria species and the detection of a potential
Page 2/2
Our reference Chyba! Nenalezen zdroj odkazů.
Date Chyba! Nenalezen zdroj odkazů.
new drug to treatment African sleeping sickness that probably disrupts the inner
mitochondrial membrane resulting in cell death of the unicellular Trypanosoma parasite.
New insights always lead to new questions. Although the majority of these will be asked at the PhD defence, hereby a few to start with.
-if the compensation mechanism of N fowleri for iron starvation is down regulation of pathways that involve iron comprising enzymes rather than increasing uptake
mechanisms (as other pathogens/organisms do), it is to be expected that N. fowleri would be more sensitive to low iron conditions. Has this been examined and is this true?
- MitoTam was shown to be an effective trypanocydal drug and it is proposed that the mechanism of action would be physicochemical disruption of the mitochondrial membrane integrity. This would require differences between the composition of the mitochondrial membranes of trypanosomes and those of mammals. Are these
compositions known, and if so can these explain the observed difference in sensitivity for MitoTam?
-under normal growth conditions the amount of copper per gram cells differs substantially (almost 3-fold) between N. gruberi and N. fowleri (fig 2A in manuscript
“Copper metabolism in Naegleria). Is the expression of copper containing ezymes higher in N. fowleri and if so which enzymes or that?
Conclusion
Hereby I approve the PhD-thesis manuscript as a dissertation, as it fulfils the following scientific requirements:
- it deals with an important scientific topic
- the research question is well defined and described - the thesis is well written and has a proper structure - the methodology is sound
- the studies resulted in new insights and views
- the introduction and discussion section of the thesis demonstrated that the candidate has proper knowledge on existing literature, theories and views
Therefore, I am looking forward to the PhD defence protocol that will take place Thursday March 23, 2023.
Sincerely,
Dr. Jaap J. van Hellemond, PhD
Associate Professor in Clinical Parasitology Head Unit Research & Education
Dept. Medical Microbiology & Infectious Diseases
