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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

To tan or not to tan: a burning issue

2009-12-08

Prof. Werner Sinclair

“Some evidence exists which implies that sunscreens could indeed be responsible for the dramatic rise in the incidence of melanoma over the past three decades, the period during which the use of sunscreens became very popular,” says Prof. Werner Sinclair, Head of the Department of Dermatology at the University of the Free State. His inaugural lecture was on the topic Sunscreens – Curse or Blessing?

Prof. Sinclair says the use of sunscreen preparations is widely advocated as a measure to prevent acute sunburn, chronic sun damage and resultant premature skin aging as well as skin malignancies, including malignant melanoma. There is inconclusive evidence to prove that these preparations do indeed achieve all of these claims. The question is whether these preparations are doing more harm than good?

He says the incidence of skin cancer is rising dramatically and these tumours are induced mostly by the ultra-violet rays.

Of the UV light that reaches the earth 90-95% belongs to the UVA fraction. UVC is normally filtered out by the ozone layer. UVB leads to sunburn while UVA leads to pigmentation (tanning). Because frequent sunburn was often associated with skin cancer, UVB was assumed, naively, to be the culprit, he says.

Exposure to sunlight induces a sense of well-being, increases the libido, reduces appetite and induces the synthesis of large amounts of vitamin D, an essential nutritional factor. The use of sunscreen creams reduces vitamin D levels and low levels of vitamin D have been associated with breast and colon cancer. Prof. Sinclair says the 17% increase in breast cancer from 1981 to 1991 parallels the vigorous use of sunscreens over the same period.

Among the risk factors for the development of tumours are a family history, tendency to freckle, more than three episodes of severe sunburn during childhood, and the use of artificial UV light tanning booths. He says it remains a question whether to tan or not. It was earlier believed that the main carcinogenic rays were UVB and that UVA merely induced a tan. The increase in UVA exposure could have severe consequences.

Prof. Sinclair says the UV light used in artificial tanning booths consists mainly of pure UVA which are highly dangerous rays. It has been estimated that six per cent of all melanoma deaths in the UK can be directly attributed to the use of artificial tanning lights. The use of an artificial tanning booth will double the melanoma risk of a person. “UVA is solely responsible for solar skin aging and it is ironical that tanning addicts, who want to look beautiful, are inflicting accelerated ageing in the process,” he says.

On the use of sunscreens he says it can prevent painful sunburn, but UVA-induced damage continues unnoticed. UVB blockers decrease vitamin D synthesis, which is a particular problem in the elderly. It also prevents the sunburn warning and therefore increases the UVA dosage that an individual receives. It creates a false sense of security which is the biggest problem associated with sunscreens.

Evidence obtained from the state of Queensland in Australia, where the heaviest and longest use of sunscreens occurred, boasted the highest incidence of melanoma in the world. A huge study in Norway has shown a 350% increase in melanoma for men and 440% for women. This paralleled the increase in the use of UVB blocking sunscreens while there was no change in the ozone layer. It did however, occur during that time when tanning became fashionable in Norway and there was an increase especially in artificial tanning.

Prof. Sinclair says: “We believe that sunscreen use does not directly lead to melanoma, but UVA exposure does. The Melanoma Epidemic is a reality. Sunscreen preparations are not the magical answer in the fight against melanoma and the irresponsible use of these preparations can worsen the problem.”

Media Release
Issued by: Mangaliso Radebe
Assistant Director: Media Liaison
Tel: 051 401 2828
Cell: 078 460 3320
E-mail: radebemt.stg@ufs.ac.za
7 December 2009

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