Antimicrobial resistance is an emerging problem, and the World Health Organization WHO has declared it one of the ten most significant threats to global health. The discussion of drug resistance is often limited to antibiotic resistance of bacteria, but the problem of antimicrobial resistance also occurs in the treatment of parasitic diseases. In addition, only a few drug options have been developed against parasites, which complicates the situation even more.
Carbonic anhydrases are metalloenzymes, i.e. enzyme proteins with a metal ion in their active center. They are everywhere in living creatures in nature. Carbonic anhydrases accelerate the hydration of carbon dioxide into carbonic acid and vice versa. This reaction is part of multiple physiological and metabolic processes, such as pH regulation and gluconeogenesis.
“In a nutshell, carbonic anhydrases work like a bottle cap in a soda or mineral water bottle: opening the cap changes the balance of the reaction, causing carbon dioxide bubbles to appear, and carbonic anhydrases also change the balance of the reaction, causing it to speed up significantly. Without carbonic anhydrases, the reaction would be too slow for physiological processes”, says Susanna Haapanen.
There are a total of eight different families of carbonic anhydrases, but the human genome has enzyme proteins from one family only. Carbonic anhydrases are being intensively investigated as new potential targets for drugs to treat various diseases.
In her dissertation, Haapanen focused on studying the carbonic anhydrases of three different parasites, Schistosoma mansoni, Entamoeba histolytica and Acanthamoeba castellanii. The infections of these parasites are common globally, but the diagnosis and treatment are often delayed. The infections can be lethal, and at their mildest, they cause a significant reduction in the quality of life. Haapanen’s goal was to improve the diagnostics and treatment of diseases caused by these parasites in the future by utilizing them.
In her research Haapanen found many promising options of carbonic anhydrase inhibitors to be further developed and tested to become clinically used drugs someday.
The results indicated that it might be possible to develop a common drug against diarrhea-causing S. mansoni and E. histolytica. This is particularly interesting because it might potentially facilitate the treatment, as S. mansoni and E. histolytica occur in the same geographic areas.
“Up to 500 million people get infected by Entamoeba histolytica and 250 million people by Schistosoma mansoni every year, so both cause significant morbidity”, Haapanen sums up.
In her doctoral research, Haapanen managed to find new solutions for the development of diagnostics as well. A. castellanii causes infection of the cornea, which can lead to blindness. In her doctoral thesis, Haapanen developed a new rapid diagnostic method for detecting A. castellanii from a sample to replace the current two-week culture.
Licentiate of Medicine Susanna Haapanen is from Tampere. She works in the Anatomy research group and specializes in internal medicine at Hatanpää hospital.
Public defence on Friday 19 January
The doctoral dissertation of MD Susanna Haapanen in the field of biomedicine titled Production, functional characterization and inhibition of carbonic anhydrases of parasites will be publicly examined in the Faculty of Medicine and Health Technology at Tampere University at 12 pm on Friday 19.1.2024 in F114 in Arvo building at Kauppi campus (Arvo Ylpön katu 34, Tampere). The Opponent will be Assistant Professor Hanna Hartikainen from University of Nottingham. The Custos will be Professor Seppo Parkkila from Tampere University.
The doctoral dissertation is available online.
The public defence can be followed via a remote connection.
Photo: Outi Haapanen