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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

Media: ANC can learn a lesson from Moshoeshoe
2006-05-20


27/05/2006 20:32 - (SA) 
ANC can learn a lesson from Moshoeshoe
ON 2004, the University of the Free State turned 100 years old. As part of its centenary celebrations, the idea of the Moshoeshoe Memorial Lecture was mooted as part of another idea: to promote the study of the meaning of Moshoeshoe.

This lecture comes at a critical point in South Africa's still-new democracy. There are indications that the value of public engagement that Moshoeshoe prized highly through his lipitso [community gatherings], and now also a prized feature in our democracy, may be under serious threat. It is for this reason that I would like to dedicate this lecture to all those in our country and elsewhere who daily or weekly, or however frequently, have had the courage to express their considered opinions on pressing matters facing our society. They may be columnists, editors, commentators, artists of all kinds, academics and writers of letters to the editor, non-violent protesters with their placards and cartoonists who put a mirror in front of our eyes.

There is a remarkable story of how Moshoeshoe dealt with Mzilikazi, the aggressor who attacked Thaba Bosiu and failed. So when Mzilikazi retreated from Thaba Bosiu with a bruised ego after failing to take over the mountain, Moshoeshoe, in an unexpected turn of events, sent him cattle to return home bruised but grateful for the generosity of a victorious target of his aggression. At least he would not starve along the way. It was a devastating act of magnanimity which signalled a phenomenal role change.

"If only you had asked," Moshoeshoe seemed to be saying, "I could have given you some cattle. Have them anyway."

It was impossible for Mzilikazi not to have felt ashamed. At the same time, he could still present himself to his people as one who was so feared that even in defeat he was given cattle. At any rate, he never returned.

I look at our situation in South Africa and find that the wisdom of Moshoeshoe's method produced one of the defining moments that led to South Africa's momentous transition to democracy. Part of Nelson Mandela's legacy is precisely this: what I have called counter-intuitive leadership and the immense possibilities it offers for re-imagining whole societies.

A number of events in the past 12 months have made me wonder whether we are faced with a new situation that may have arisen. An increasing number of highly intelligent, sensitive and highly committed South Africans across the class, racial and cultural spectrum confess to feeling uncertain and vulnerable as never before since 1994. When indomitable optimists confess to having a sense of things unhinging, the misery of anxiety spreads. It must have something to do with an accumulation of events that convey the sense of impending implosion. It is the sense that events are spiralling out of control and no one among the leadership of the country seems to have a handle on things.

I should mention the one event that has dominated the national scene continuously for many months now. It is, of course, the trying events around the recent trial and acquittal of Jacob Zuma. The aftermath continues to dominate the news and public discourse. What, really, have we learnt or are learning from it all? It is probably too early to tell. Yet the drama seems far from over, promising to keep us all without relief, and in a state of anguish. It seems poised to reveal more faultlines in our national life than answers and solutions.

We need a mechanism that will affirm the different positions of the contestants validating their honesty in a way that will give the public confidence that real solutions are possible. It is this kind of openness, which never comes easily, that leads to breakthrough solutions, of the kind Moshoeshoe's wisdom symbolises.

Who will take this courageous step? What is clear is that a complex democracy like South Africa's cannot survive a single authority. Only multiple authorities within a constitutional framework have a real chance. I want to press this matter further.

Could it be that part of the problem is that we are unable to deal with the notion of "opposition". We are horrified that any of us could become "the opposition". In reality, it is time we began to anticipate the arrival of a moment when there was no longer a single [overwhelmingly] dominant political force as is currently the case. Such is the course of change. The measure of the maturity of the current political environment will be in how it can create conditions that anticipate that moment rather than ones that seek to prevent it. This is the formidable challenge of a popular post-apartheid political movement.

Can it conceptually anticipate a future when it is no longer overwhelmingly in control, in the form in which it currently is and resist, counter-intuitively, the temptation to prevent such an eventuality? Successfully resisting such an option would enable its current vision and its ultimate legacy to our country to manifest itself in different articulations of itself, which then contend for social influence.

In this way, the vision never really dies, it simply evolves into higher, more complex forms of itself. If the resulting versions are what is called "the opposition" that should not be such a bad thing - unless we want to invent another name for it. The image of flying ants going off to start other similar settlements is not so inappropriate.

I do not wish to suggest that the nuptial flights of the alliance partners are about to occur: only that it is a mark of leadership foresight to anticipate them conceptually. Any political movement that has visions of itself as a perpetual entity should look at the compelling evidence of history. Few have survived those defining moments when they should have been more elastic, and that because they were not, did not live to see the next day.

I believe we may have reached a moment not fundamentally different from the sobering, yet uplifting and vision-making, nation-building realities that led to Kempton Park in the early 1990s. The difference between then and now is that the black majority is not facing white compatriots across the negotiating table. Rather, it is facing itself: perhaps really for the first time since 1994. It is not a time for repeating old platitudes. Could we apply to ourselves the same degree of inventiveness and rigorous negotiation we displayed up to the adoption or our Constitution?

Morena Moshoeshoe faced similarly formative challenges. He seems to have been a great listener. No problem was too insignificant that it could not be addressed. He seems to have networked actively across the spectrum of society. He seems to have kept a close eye on the world beyond Lesotho, forming strong friendships and alliances, weighing his options constantly. He seems to have had patience and forbearance. He had tons of data before him before he could propose the unexpected. He tells us across the years that moments of renewal demand no less.

  • This is an editied version of the inaugural Moshoeshoe Memorial Lecture presented by Univeristy of Cape Town vice-chancellor Professor Ndebele at the University of the Free State on Thursday. Perspectives on Leadership Challenges In South Africa

 

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