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UFS researchers investigate deadly fungi affecting millions in South Africa

12 June 2023 | Story André Damons | Photo Sonia Small

Prof Carolina Pohl-Albertyn — Prof Carlien Pohl-Albertyn, National Research Forum (NRF) SARChI Research Chair in Pathogenic Yeasts, leads the research team that is working on various research projects relating to fungi casing yeast.

Fungal infections affect more than one billion people each year, of which more than 150 million cases are severe and life-threatening, causing 1.7 million deaths a year. In South Africa it is estimated that diseases caused by fungal infections total more than three million cases a year. These figures are especially shocking given that prior to 1980, fungal infections were not a major health problem. The WHO has recently published a list of priority pathogens in which fungi are classified in critical, high- and medium- priority groups. Candida species are found in all three levels and Cryptococcus species in critical and medium groups,” says Prof Pohl-Albertyn.

It is for these reasons that researchers in the Department of Microbiology and Biochemistry at the University of the Free State (UFS) are working on various research projects investigating new treatment options beyond the established antifungals. Prof Carlien Pohl-Albertyn, National Research Forum (NRF) SARChI Research Chair in Pathogenic Yeasts, leads the team that is working on various research projects relating to fungi casing yeast.

Multidrug-resistant yeast

One of the yeasts being researched is Candida auris – a multidrug-resistant yeast that can cause severe infections in humans, particularly in people who are hospitalised or have weakened immune systems. C. auris was first identified in 2009 in Japan and has since been reported in over 49 countries.

According to Prof Pohl-Albertyn, C. auris is of concern because it is often resistant to multiple antifungal drugs, making it difficult to treat. In addition, it can survive on surfaces in healthcare settings, which can contribute to its spread between patients, causing outbreaks in hospitals. “Due to its multidrug resistance and potential for transmission, C. auris has been designated by the Centers for Disease Control and Prevention (CDC) as a serious global health threat and listed as the second most critical fungal pathogen in the World Health Organisation (WHO) fungal critical priority group.

“C. auris possesses virulence factors such as increased thermotolerance, high salinity tolerance, biofilm formation, and extra cellular enzyme secretion, which are the major contributing factors to its multidrug resistance profile and virulence. Even though C. auris has a variety of virulence factors that it employs against its human host to develop an infection, its virulence mechanisms remain unclear,” says Prof Pohl-Albertyn.

Therefore, several research projects investigate this pathogenic yeast. All of them started with the development of CRISP-Cas9 gene editing tools for this yeast, in order to be able to delete specific genes in this yeast to study their roles. These tools are also constantly being improved for greater efficiency by students under the supervision of Prof Koos Albertyn. Two current projects deal with the function of specific secreted enzymes in the virulence of C. auris.

Environmental yeast

Another yeast being researched, under the supervision of Prof Olihile Sebolai, is Cryptococcus neoformans, an environmental yeast found in trees and soil contaminated with bird droppings. Moreover, it can be airborne and when inhaled it lodges in the lungs (in alveoli) and can cause primary lung infection, explains Prof Pohl-Albertyn.

Cryptococcus neoformans causes AIDS-defining illnesses in people living with HIV/AIDS. To the point, it was not surprising when the WHO declared it as the first critical fungal pathogen of concern. Dissemination to other organs has been reported where it crosses the epithelium barrier by secreting proteases (a class of enzymes that break down proteins in the host) that compromise the tight junctions between the epithelial cells.

The current projects investigate the interaction between the proteases secreted by C. neoformans and co-infecting viruses, such as SARS-CoV-2 and influenza. The SARS-CoV-2 virus is activated by proteases in the host and proteases also help the influenza virus to enter and infect the host cells. Since the host proteases are similar to those secreted by C. neoformans, these projects are focused on determining if the yeast proteases can also help the viruses to cause infection. This project is also extended to study Candida albicans proteases as this is also a common co-infecting yeast in COVID-19 patients (for more detail on C. albicans).

Another project looks at the application of plants as sources for novel drugs against C. neoformans. This is important since 75-80% of African and Asian populations still rely on traditional or complementary/alternative medicines for their primary health-care needs. Coupled to this, modern medicines have become increasingly expensive and thus inaccessible to many in developing countries. Moreover, there is a shift to more “organic” and “vegan” lifestyles as well as the use of herbal medicines to prevent or manage the development of certain diseases.

Yeast contaminated water

“Considering the severity of invasive fungal infection, it is important to study the dissemination and proliferation of various pathogenic or potentially pathogenic fungal species in our surrounding environments. It is crucial to identify major vectors that aid in the spread of pathogenic yeast to prevent infections in susceptible individuals, which mainly include immunocompromised or immunosuppressed individuals.

“Candida, Cryptococcus and Rhodotorula species are commonly found in a variety of water sources with which humans are in frequent contact through daily activities like bathing, washing of clothes and cooking. This recent information further warrants the investigation into the possibility that fungal infections may occur through contact with yeast contaminated water,” concludes Prof Pohl-Albertyn.

She says it is thus important to investigate the presence and antifungal susceptibility of yeast found in water as well as to identify ways to monitor potential fungal outbreaks, possibly through wastewater surveillance. The research aims to identify potentially pathogenic yeast species as well as to quantify levels of azole, specifically fluconazole, in wastewater. In addition, the fluconazole susceptibility of these isolates will be assessed in an attempt to link azole pollution of the environment to antifungal drug resistance development.

News Archive

Studies to reveal correlation between terrain, energy use, and giraffe locomotion

2016-11-18

More than half of giraffes in captivity in Europe are afflicted by lameness. This high prevalence represents an important welfare issue, similar to other large zoo animals.

According to Dr Chris Basu, a veterinarian at the Royal Veterinary College in the UK, giraffes in captivity are often afflicted by overgrown hooves, laminitis and joint problems. Diagnosis and treatment is limited by our understanding of anatomy and function, more specifically the locomotion of these animals. Although the giraffe is such a well-known and iconic animal, relatively little has been studied about their locomotor behaviour.

Dr Basu recently visited South Africa to do fieldwork on the locomotion of giraffes as part of his PhD studies under the mentorship of world-renowned Professor of Evolutionary Biomechanics, Prof John Hutchinson. This project is a joint venture between Dr Basu and Dr Francois Deacon, researcher in the Department of Animal, Wildlife, and Grassland Sciences at the UFS. Dr Deacon is a specialist in giraffe habitat-related research.

Together Prof Hutchinson and Drs Deacon and Basu form a research group, working on studies about giraffe locomotion.

Wild giraffe population decrease by 40% in past decade

“Locomotion is one of the most common animal behaviours and comes with a significant daily energetic cost. Studying locomotion of wild animals aids us in making estimates of this energetic cost. Such estimates are useful in understanding how giraffes fit into ecosystems. Future conservation efforts will be influenced by knowledge of the energy demands in giraffes.

“Understanding aspects of giraffe locomotion also helps us to understand the relationships between anatomy, function and evolution. This is relevant to our basic understanding of the natural world, as well as to conservation and veterinary issues,” said Dr Deacon.

Locomotion study brings strategy for specialist foot care

On face value it seems as if foot disease pathologies are more common in zoo giraffes than in wild giraffes. “However, we need a good sample of data from both populations to prove this assumption,” said Dr Basu.

This phenomenon is not well understood at the moment, but it’s thought that diet, substrate (e.g. concrete, straw, sand and grass) and genetics play a part in foot disease in giraffes. “Understanding how the feet are mechanically loaded during common activities (standing, walking, running) gives our research group ideas of where the highest strains occur, and later how these can be reduced through corrective foot trimming,” said Dr Basu.

Through the studies on giraffe locomotion, the research group plans to devise strategies for corrective foot trimming. At the moment, foot trimming is done with the best evidence available, which is extrapolation from closely related animals such as cattle. “But we know that giraffes’ specialist anatomy will likely demand specialist foot care,” Dr Basu said.

Studying giraffes in smaller versus larger spaces

The research group has begun to study the biomechanics of giraffe walking by looking at the kinematics (the movement) and the kinetics (the forces involved in movement) during walking strides. For this he studied adult giraffes at three zoological parks in the UK.

However, due to the close proximity of fencing and buildings, it is not practical to study fast speeds in a zoo setting.

A setting such as the Willem Pretorius Nature Reserve, near Ventersburg in the Free State, Kwaggafontein Nature Reserve, near Colesberg in the Karoo, and the Woodland Hills Wildlife Estate in Bloemfontein are all ideal for studying crucial aspects such as “faster than walking” speeds and gaits to measure key parameters (such as stride length, step frequency and stride duration). These studies are important to understand how giraffe form and function are adapted to their full range of locomotor behaviours. It also helps to comprehend the limits on athletic capacity in giraffes and how these compare to other animals.

Drones open up unique opportunities for studying giraffes

The increasing availability of unmanned aerial vehicles (UAVs)/drones opens up unique opportunities for studying locomotion in animals like giraffes. Cameras mounted onto remotely controlled UAVs are a straightforward way to obtain high-quality video footage of giraffes while they run at different speeds.

“Using two UAVs, we have collected high definition slow motion video footage of galloping giraffes from three locations in the Free State. We have also collected detailed information about the terrain that the giraffes walked and ran across. From this we have created 3D maps of the ground. These maps will be used to examine the preferred terrain types for giraffes, and to see how different terrains affect their locomotion and energy use,” said Dr Deacon.

“The raw data (videos) will be digitised to obtain the stride parameters and limb angles of the animals. Later this will be combined with anatomical data and an estimation of limb forces to estimate the power output of the limbs and how that changes between different terrains,” said Dr Basu.

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