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scientist unveils "secret weapon" of superbug that infects intestine

 With the discovery of an "armor structure", the study envisages "new possibilities for the development of innovative therapies" that attack the C. diff bacterium with "minimal effects".

A team of scientists, including the Portuguese Paula Salgado, discovered that the superbug C. diff, which infects the intestine, has a compact layer of proteins that promotes its resistance to antibiotics, was released this Friday.

The study, by revealing the structure of this “armor” and its “potential weaknesses” , provides “new possibilities for the development of innovative therapies” that attack the bacteria with “minimal effects” on the intestinal microbiome, Paula Salgado told Lusa, who directs the structural microbiology research group on C. diff at the British University of Newcastle.

Bacteria have a layer of proteins that covers the cells, but that of C. diff “is very compact, with very narrow openings that prevent most molecules from entering”, which may explain, according to biochemistry, the success of this superbug “in defending itself against the response of the immune system and currently available antibiotics”.

Paula Salgado pointed out that C. diff can “resist practically all antibiotics, with only three being effective”.

However, many patients experience reinfections, as the antibiotics administered attack the beneficial bacteria in the gut (which are part of the microbiome, the community of microorganisms that live in the gut) while treating infections, “creating the conditions for C. diff grow and cause problems”.

“New therapies are needed, specific against C. diff, that attack the infection with minimal effects on the healthy microbiome”, pointed out the Portuguese researcher, pointing out that therapeutic strategies may involve new drugs or viruses that infect the bacteria (bacteriophages) .

The idea is to “break” the “armor” of C. diff and create “holes” that allow drugs or bacteriophages to enter and kill the bacterial cell.

C. diff is a superbug – so named because of its multi-resistance to antibiotics – that causes severe diarrhea and, in the most severe cases, death as a result of various injuries to the walls of the intestine.

The work signed by Paula Salgado and colleagues from other British universities, and published this Friday in the scientific journal Nature Communications, shows that the proteins of the layer that covers the bacterial cell “fit together” to form a “tight mesh”.

The team of scientists determined the structure of the main protein that makes up this layer, SlpA, and how “the different molecules interact and fit together” to form this “mesh”.

The study authors used X-ray crystallography techniques to obtain the structure of the SlpA protein and electron microscopy techniques to reveal the structure of the "armor" in the bacterial cell.

Paula Salgado and her research group worked directly within the structure of SlpA.

“I started this work more than 10 years ago, having obtained the first SlpA crystals. Our team optimized the crystals, collected the data and managed to solve the various technical problems until obtaining the complete structure of SlpA”, described the biochemist to Lusa.

In upcoming studies, Paula Salgado and colleagues who signed the investigation published this Friday want to understand “how molecules enter and leave” the C. diff cell, since it is surrounded by a compact, albeit flexible, layer of proteins. .

“Nutrients have to be able to enter the bacterial cell so that it can grow and divide. C. diff produces toxins, responsible for the lesions in the intestines, which have to be released to the outside of the cell”, pointed out the Portuguese researcher.Scientists also want to know the role of the compact layer of proteins in the bacterial cell in infection and in the interaction with intestinal cells and the immune system.

Most cases of C. diff are associated with taking antibiotics , but there are other risk factors, such as age (65 years or older), weakened immune system (such as transplant patients, cancer patients or HIV/AIDS patients) and hospital admissions.

Symptoms such as fever, severe diarrhea, loss of appetite, nausea, and stomach pain may occur a few days after starting an antibiotic.


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