A systematic review in non-clinical research: a case of pathogen metabolites

Posted by Kasra

Doctors and scientists in the field of clinical research are well acquainted to systematic reviews and their importance in clinical research. The important difference between a normal review and a systematic review is that in the latter the authors make sure (or at least try very hard) to include and cover all the published research about the topic of review. Along with the review of the data, they should also publish the search strategy they used to make sure they get everything that has been published about their topic of study. Collecting all the data is extremely important especially when deciding about the beneficial effects of a certain drug, vaccine or public health intervention.  The Cochrane collaboration is a well-known organisation that collects and publishes systematic reviews in field of health research and health care.

Although they could be very useful in non-clinical research, systematic reviews are actually rarely written in these fields. During my graduate studies, I had to write a systematic review on innate receptors for a certain fungus. I realized then how diverse the experimental models are and how hard it is compare their controversial results due to small or big differences in experimental setup and strains used. Maybe that is why these papers are rare in non-clinical research. Still, no matter how hard, I was able to do it with as much time as a graduate student would put on a term paper and get a good grade for it ;). I am looking forward to reading more non-clinical systematic reviews.

Recent work of Bos et al. is an excellent example of how useful it could be to gather all the available data in a certain field, even if it is not all clinical trials. They point to most common abundant bacteria in sepsis Staphylococcus aureus (SA), Streptococcus pneumoniae (SP), Enterococcus faecalis (EF), Pseudomonas aeruginosa (PA), Klebsiella pneumoniae (KP), and Escherichia coli (EC). They argue that current strain detection methods are too slow and do not allow for efficient targeted antibiotic therapy. On the other hand, non-targeted therapy is not always successful. They argue that the unique and some-what well-identified metabolic pathways of these bacteria leads to production of certain volatile chemicals that are not produced by humans and could be used as rapid diagnostic markers. The diagram below shows the gram positive bacteria on the left and gram negative bacteria on the right, graphing unique and common volatile chemicals they produce. The blue circle in the center shows the chemicals produced by all bacteria. Therefore, their absence would exclude infection. The red (or pink as you may) circles highlight the unique products of each species which could help in targeted antibiotic therapy of sepsis.

Staphylococcus aureus (SA), Streptococcus pneumoniae (SP), Enterococcus faecalis (EF), Pseudomonas aeruginosa (PA), Klebsiella pneumoniae (KP), and Escherichia coli (EC)

Bos, L., Sterk, P., & Schultz, M. (2013). Volatile Metabolites of Pathogens: A Systematic Review PLoS Pathogens, 9 (5) DOI: 10.1371/journal.ppat.1003311

What happens during differentiation of Leishmania? From a metabolism point of view

Posted by Kasra Hassani

The differentiation of the promastigote Leishmania to the amastigote form is one of the most interesting and promising areas of study in Leishmania research. Researchers are interested to know what are the differences between these two life-stages, how do the parasites shift from one to the other and what happens during this transformation. Rosenzweig et al. have addressed these questions by proteomic comparison of Leishmania donovani’s proteome during its transformation from the promastigote to the amastigote form. Using a new labelling method called the iTRAQ, they have looked at the proteome of L. donovani after stimulation with low pH and high temperature within 2.5, 5, 10, 15, 24h and after 6 days. With their method they believe that they have been able to detect half of the parasite’s proteome. This study has shown key changes in the proteome content of L. donovani which corresponds with its metabolic needs in the phagolysosome.

The mid-gut of sandfly is a sugar-rich environment because of its nectar-diet supplemented with occasional bloodmeals. However, sugars are scarce in the phagolysosome and the parasite has to switch to fatty acids and amino acids as energy sources. According to Rosenzweig et al., starting from 10h after stimulation, glycolysis enzymes are down-regulated while enzymes required for beta-oxidation, gluconeogenesis, amino acid catabolism, TCA cycle and mitochondrial respiration are up-regulated. Furthermore, protein translation and thus metabolism slows down which corresponds to parasite’s smaller size and slower growth. In this way the parasite retools its metabolism to be able to live and multiply inside the phagolysosome. Another interesting and rather surprising finding of Rosenzweig et al. is that most of these alterations in metabolism start rather late (after 10-15h) and they take hours to maturate. This finding, raises the question that how do incompletely differentiated parasites reside in the same host environment as the mature amastigotes?