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22 February 2024 | Story André Damons | Photo SUPPLIED
Prof Robert Bragg
Prof Robert Bragg is a researcher in the Department of Microbiology and Biochemistry at the University of the Free State (UFS) and believes hospital-acquired infections (HAIs) might already be “Disease X”.

During the World Governments Summit, the World Health Organisation (WHO) warned world leaders about the likelihood of a Disease X outbreak, saying it is “a matter of when, not if” a new pathogen and pandemic will strike. If there is an outbreak of this disease tomorrow, the world still would not be ready. 

During his speech earlier this month at the summit in Dubai, Tedros Adhanom Ghebreyesus, Director-General of the WHO, said COVID-19 was a Disease X – a new pathogen causing a new disease. He said: “There will be another Disease X, or a Disease Y or a Disease Z. And as things stand, the world remains unprepared for the next Disease X, and the next pandemic. If it struck tomorrow, we would face many of the same problems we faced with COVID-19.”

Though Disease X is a hypothetical placeholder representing yet-to-be-encountered pathogens, Prof Robert Bragg, researcher in the Department of Microbiology and Biochemistry at the University of the Free State (UFS), believes hospital-acquired infections (HAI) might already be “Disease X”. He says data shows that deaths from HAIs will become the leading cause of human deaths. This problem is rapidly growing as most of the pathogens which people contract while in hospital are now resistant to antibiotics, making them very difficult to treat.  

Prof Bragg, whose main research is in disease-control, first in the agricultural industry, and now human health, also previously warned about a disease that would make COVID-19, which killed more than seven million people to date globally, look like a dress rehearsal. His PhD student, Samantha Mc Carlie, investigating how bacteria become resistant to disinfectant and sanitiser products. This is a serious problem for the future, as disinfection could be our last line of defence.

Heading for a crisis in health care

“The world is rapidly heading for a crisis in health care regarding hospital-acquired infections. It is common knowledge that we are quickly running out of antibiotics (and antifungals) to treat bacterial and yeast infections. Without antibiotics and antifungals, the outcome of many of these bacterial and yeast hospital-acquired infections will be very severe. They will, unfortunately, in many cases, result in the death of the patient,” says Prof Bragg. 

According to him, the WHO suggests that 30% of patients in ICUs in developed countries and 70% in underdeveloped countries will contract a HAI. Of these, the mortality rate can be as high as 70%. 

“Most of these infections are caused by multiple drug resistance strains of bacteria such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species. Additional bacteria and yeast, which can also cause HAIs, such as Serratia species, are also becoming a concern due to their intrinsic higher levels of disinfectant resistance.”

Prof Bragg explains that in 2014, a high-profile review was first published, commissioned by the UK Prime Minister, entitled, “Antimicrobial Resistance: Tackling a crisis for the Health and Wealth of Nations” (the AMR Review). This review estimated that antimicrobial resistance (AMR) could cause 10 million deaths annually by 2050 (The Review on Antimicrobial Resistance 2016). This is the same number of deaths caused by cancer today, making AMR the leading cause of human mortality by 2050. When it was finalised, this report was highly criticised as an over-dramatisation, as when this prediction was made, the number of mortalities related to HAIs was around 700 000 – a very long way off 10 000 000. However, according to recent estimates, five years later, in 2019, 1.27 million deaths were directly attributed to drug-resistant infections globally, and this had reached 4.95 million deaths associated with bacterial AMR (including those directly attributable to AMR) by 2022 (Murray et al. 2022). 

The overuse of disinfectants during the COVID-19 pandemic, according to Prof Bragg and Mc Calie, has contributed to the crisis by fostering resistant strains and contaminating environments. Based on the current trajectory of mortalities, the 10 million mark will be reached way before 2050.

Need for a paradigm shift

The researchers say an urgent need to change the paradigm in medicine from “treatment” to “prevention” is necessary and that the old saying ‘prevention is better than cure’ has never been truer. 

According to Bragg: “The golden era of antibiotics is rapidly coming to an end. It is highly unlikely that we will discover new antibiotics, and even if we do, the likelihood that the bacteria will already have or will be able to develop resistance in a very short time is highly likely. 

“We need to think of what happed with quinolones, where we thought we had won the war with a groundbreaking new antimicrobial agent. The bacteria did not have millions of years of evolution to develop resistance to quinolone, yet in only three years, the first resistant bacteria were isolated. There is currently great excitement around AI-derived new antibiotics. However, the end result is likely to be the same. We need an alternative to treatment – in other words, a paradigm shift.” 

Improved biosecurity 

Prof Bragg says highly improved biosecurity is the only viable option for disease control in a post-antibiotic era. By using good biosecurity in poultry production, he says the mortality rates were reduced by 50%. 

Research has shown a direct link between the environmental microbial load in a hospital and HAIs; with a lower microbial load linked to lower incidence of HAIs including C. difficile infections (Boyce et al. 2008; Suleyman et al. 2018; Umemura et al., 2022). Therefore, the new paradigm is to reduce microbial contamination in the hospital environment to prevent HAIs. If there are fewer dangerous microorganisms in an environment, patient and staff exposure to these microorganisms will decrease, reducing the level of HAIs for staff and patients. However, to reduce the microbial loads in healthcare settings, effective cleaning and disinfection products need to be used. 

News Archive

UFS study on cell development in top international science journal
2008-09-16

A study from the University of the Free State (UFS) on how the change in the packaging of DNA with cell development influenced the expression of genes, will be published in this week’s early edition of the prestigious international, peer-reviewed science journal, the Proceeding of the National Academy of Sciences of the USA (PNAS).

The PNAS journal has an impact factor of 10, which means that studies published in the journal are, on average, referred to by ten other scientific studies in a two year period. The South African Journal of Science, by comparison, has an impact factor of 0.7.

The UFS study, funded by the Wellcome Trust and the National Research Foundation (NRF), looked at how the change in the packaging of DNA with cell development influenced the expression of genes. It is very relevant to research on stem cells, an area of medicine that studies the possible use of undifferentiated cells to replace damaged tissue.

Prof. Hugh Patterton, of the Department of Microbial, Biochemical and Food Biotechnology at the UFS, who led the study, said: "We are extremely proud of this study. It was conceived in South Africa, it was performed in South Africa, the data were analysed in South Africa, and it was published from South Africa."

When a gene is expressed, the information encoded in the gene is used to manufacture a specific protein. In eukaryotes, which include humans, there is approximately 1m of DNA, containing the genes, in every cell. This length of DNA has to fit into a cell nucleus with a diameter of only about 10 micrometer. In order to fit the DNA into such a small volume, eukaryotic cells wrap their DNA onto successive protein balls, termed nucleosomes. Strings of nucleosomes, resembling a bead of pearls, is folded into a helix to form a chromatin fiber. The study from the UFS investigated how the binding of a specific protein, termed a linker histone, that binds to the length of DNA between nucleosomes, influenced the formation of the chromatin fiber and also the activity of genes.

"We found that the linker histone bound to chromatin in yeast, which we use as a model eukaryote, under conditions where virtually all the genes in the organism were inactive. It was widely believed that the binding of the linker histone caused the inactivation of genes. We studied the relationship between the amount of linker histone bound in the vicinity of each gene and the expression of that gene for all the genes in yeast, using genomic techniques. We made the surprising discovery that even through the linker histone preferentially bound to genes under conditions where the genes were shut off, this inactivation of genes was not caused by the binding of the linker histone and folding of the chromatin,” said Prof. Patterton.

He said: “Instead our data strongly suggested that the observed anti-correlation was due to the movement of enzymes along the DNA molecule, involved in processing the information in genes for the eventual manufacture of proteins. This movement of enzymes displaced the linker histones from the DNA. This finding now requires a rethink on aspects of how packaging of DNA influences gene activity."

Prof. Patterton said that his research group, using the Facility for Genomics and Proteomics as well as the Bioinformatics Node at the UFS, was currently busy with follow-up studies to understand how other proteins in nucleosomes affected the activities of genes, as well as with projects to understand how chemicals found in red wine and in green tea extended lifespan. "We are certainly having a marvelous time trying to understand the fundamental mechanisms of life, and the UFS is an exciting place to be if one was interested in studying life at the level of molecules," he said.


Media Release
Issued by: Lacea Loader
Assistant Director: Media Liaison
Tel: 051 401 2584
Cell: 083 645 2454
E-mail: loaderl.stg@ufs.ac.za  
18 September 2008
 

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