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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: Sunday Times
2006-05-20

Sunday Times, 4 June 2006

True leadership may mean admitting disunity
 

In this edited extract from the inaugural King Moshoeshoe Memorial Lecture at the University of the Free State, Professor Njabulo S Ndebele explores the leadership challenges facing South Africa

RECENT events have created a sense that we are undergoing a serious crisis of leadership in our new democracy. An increasing number of highly intelligent, sensitive and committed South Africans, across class, racial and cultural spectrums, 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. We have the sense that events are spiralling out of control and that no one among the leadership of the country seems to have a definitive handle on things.

There can be nothing more debilitating than a generalised and undefined sense of anxiety in the body politic. It breeds conspiracies and fear.

There is an impression that a very complex society has developed, in the last few years, a rather simple, centralised governance mechanism in the hope that delivery can be better and more quickly driven. The complexity of governance then gets located within a single structure of authority rather than in the devolved structures envisaged in the Constitution, which should interact with one another continuously, and in response to their specific settings, to achieve defined goals. Collapse in a single structure of authority, because there is no robust backup, can be catastrophic.

The autonomy of devolved structures presents itself as an impediment only when visionary cohesion collapses. Where such cohesion is strong, the impediment is only illusory, particularly when it encourages healthy competition, for example, among the provinces, or where a province develops a character that is not necessarily autonomous politically but rather distinctive and a special source of regional pride. Such competition brings vibrancy to the country. It does not necessarily challenge the centre.

Devolved autonomy is vital in the interests of sustainable governance. The failure of various structures to actualise their constitutionally defined roles should not be attributed to the failure of the prescribed governance mechanism. It is too early to say that what we have has not worked. The only viable corrective will be in our ability to be robust in identifying the problems and dealing with them concertedly.

We have never had social cohesion in South Africa — certainly not since the Natives’ Land Act of 1913. What we definitely have had over the decades is a mobilising vision. Could it be that the mobilising vision, mistaken for social cohesion, is cracking under the weight of the reality and extent of social reconstruction, and that the legitimate framework for debating these problems is collapsing? If that is so, are we witnessing a cumulative failure of leadership?

I am making a descriptive rather than an evaluative inquiry. I do not believe that there is any single entity to be blamed. It is simply that we may be a country in search of another line of approach. What will it be?

I would like to suggest two avenues of approach — an inclusive model and a counter-intuitive model of leadership.

In an inclusive approach, leadership is exercised not only by those who have been put in some position of power to steer an organisation or institution. Leadership is what all of us do when we express, sincerely, our deepest feelings and thoughts; when we do our work, whatever it is, with passion and integrity.

Counter-intuitive leadership lies in the ability of leaders to read a problematic situation, assess probable outcomes and then recognise that those outcomes will only compound the problem. Genuine leadership, in this sense, requires going against probability in seeking unexpected outcomes. That’s what happened when we avoided a civil war and ended up with an “unexpected” democracy.

Right now, we may very well hear desperate calls for unity, when the counter-intuitive imperative would be to acknowledge disunity. A declaration of unity where it manifestly does not appear to exist will fail to reassure.

Many within the “broad alliance” might have the view that the mobilising vision of old may have transformed into a strategy of executive steering with a disposition towards an expectation of compliance. No matter how compelling the reasons for that tendency, it may be seen as part of a cumulative process in which popular notions of democratic governance are apparently undermined and devalued; and where public uncertainty in the midst of seeming crisis induces fear which could freeze public thinking at a time when more voices ought to be heard.

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 be seen to have become “the opposition”. The word has been demonised. In reality, it is time we began to anticipate the arrival of a moment when there is no longer a single, overwhelmingly dominant political force as is currently the case. Such is the course of history. The measure of the maturity of the current political environment will be in how it can create conditions that anticipate that moment rather than seek to prevent it. We see here once more the essential creativity of the counter-intuitive imperative.

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 is currently, 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 in different articulations, which then contend for social influence. In this way, the vision never really dies; it simply evolves into higher, more complex forms of itself. Consider the metaphor of flying ants replicating the ant community by establishing new ones.

We may certainly experience the meaning of comradeship differently, where we will now have “comrades on the other side”.

Any political movement that imagines itself as a perpetual entity should look at the compelling evidence of history. Few movements 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 ’90s. 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. Could we apply to ourselves the same degree of inventiveness and rigorous negotiation we displayed leading up to the adoption or our Constitution?

This is not a time for repeating old platitudes. It is the time, once more, for vision.

In the total scheme of things, the outcome could be as disastrous as it could be formative and uplifting, setting in place the conditions for a true renaissance that could be sustained for generations to come.

Ndebele is Vice-Chancellor of the University of Cape Town and author of the novel The Cry of Winnie Mandela

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