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Friday, October 07, 2022

Study provides clues about the transformation of harmless environmental bacterium into a dangerous pathogen

Hospital-acquired infections (HAIs) are often particularly difficult to treat because pathogens have developed resistance to common antibiotics.

The bacterium Acinetobacter baumannii is particularly dangerous in this regard, and research is seeking new therapeutic approaches to combat it. To look for suitable starting points, an international team led by bioinformaticians at the Goethe University Frankfurt has compared thousands of genomes of pathogenic and harmless Acinetobacter strains. This has provided clues as to what qualities made A. baumannii a successful pathogen – and how it could possibly be combated.

Each year, more than 670,000 people in Europe fall ill with pathogenic bacteria that exhibit antibiotic resistance, and 33,000 die from the diseases they cause. Particularly feared are pathogens that are resistant to several antibiotics at the same time. bacteria among them Acinetobacter baumanniiWhich today tops out as a “hospital superbug”: up to five percent of all hospital-acquired bacterial infections are caused by this germ alone.

a. dwarf Tops the list of candidates for which, according to the World Health Organization (WHO), new treatments should be developed. This is because the pathogen – due to a flexible genome – easily acquires new antibiotic resistance.

At the same time, infections are not only happening more and more outside the hospital environment, but are also leading to increasingly serious progress. However, a prerequisite for the development of new therapeutic approaches is that we understand what properties make up a. dwarf and its human pathogenic relative, known as Acinetobacter (acb) Complex, a pathogen.

A team led by bioinformatician Professor Ingo Ebersberger from the Goethe University Frankfurt/Lowe Center for Translational Biodiversity Genomics (LOEWE-TBG) has now reached a milestone in this understanding. The team is made up of members of Research Unit 2251 of the German Research Foundation and other national and international partners, including scientists from Washington University School of Medicine, St. Louis, USA.

For their analysis, the team used the fact that a large proportion of the members dwarf The genus are harmless environmental bacteria that live in water or on plants or animals. Thousands of complete genome sequences for both these as well as pathogens dwarf The strains are stored in a publicly accessible database.

By comparing these genomes, the researchers were able to systematically filter out differences between pathogenic and harmless bacteria. Because the occurrence of individual genes was not particularly conclusive, Ebersberger and colleagues focused on gene clusters, that is, groups of neighboring genes that have remained stable during evolution and may form a functional unit. “Of these evolutionarily stable gene clusters, we identified 150 that are present in pathogenic dwarf rare or absent in the strains and their non-pathogenic relatives,” Ebersberger says, summarizingly. “It is highly likely that these gene clusters benefit the survival of pathogens in the human host.”

Among the most important properties of pathogens are their ability to form protective biofilms and to efficiently absorb micronutrients such as iron and zinc. And indeed, the researchers found that the uptake systems in the ACB group were a reinforcement of existing and evolutionary old uptake mechanisms.

Particularly exciting is the fact that pathogens apparently exploit a particular source of energy: they can break down the carbohydrate kynurenine produced by humans, which as a messenger substance modulates the innate immune system. The bacteria apparently kill two birds with one stone in this way. On the one hand, breaking down kynurenine supplies them with energy, and on the other, they can potentially use it to control the host’s immune response.

Our work marks a milestone in understanding what is different about the pathogenic Acinetobacter baumannii. Our data is of such high resolution that we can even see the situation in different forms. This knowledge can now be used to develop specific treatments against which resistance does not yet exist with all probability.,


Ingo Ebersberger, Professor, LOEWE Center for Translational Biodiversity Genomics, Goethe University Frankfurt

Source:

Geothe University Frankfurt

Journal Reference:

Jahanschiri, B., and others, (2022) sheds light on common basis of pathogenicity in evolutionary stable gene clusters Acinetobacter Complex. plus genetics, doi.org/10.1371/journal.pgen.1010020

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