Study offers clues on shift from harmless environmental bacteria to a dreaded pathogen

Hospital-acquired infections (HAIs) are often particularly difficult to treat because the pathogens have become resistant to many common antibiotics.

The bacterium Acinetobacter baumannii in particular is feared in this regard and research is seeking new therapeutic approaches to combat it. To find suitable starting points, an international team led by bioinformatics scientists from Goethe University Frankfurt compared thousands of genomes of pathogenic and harmless Acinetobacter strains. This has provided clues as to what traits may have made A. baumannii a successful pathogen — and how it could potentially be controlled.

Each year, more than 670,000 people in Europe are sickened by pathogenic bacteria that show resistance to antibiotics, and 33,000 die from the diseases they cause. Particularly feared are pathogens that are resistant to several antibiotics at the same time. Among them is the bacteria Acinetobacter baumanniiwhich is now mainly feared as a “hospital superbug”: up to five percent of all hospital-acquired bacterial infections are caused by this germ alone.

A. baumannii is at the top of the list of candidates for which new therapies should be developed according to the World Health Organization (WHO). This is because the pathogen – through a flexible genome – easily acquires new antibiotic resistance.

At the same time, infections are not only increasingly common outside the hospital setting, but also lead to an increasingly severe progression. However, a precondition for the development of new therapeutic approaches is an understanding of which properties the A. baumannii and its human pathogenic relatives, grouped into what is known as the Acinetobacter calcoaceticus baumannii (ACB) complex, a pathogen.

A team led by bioinformatician Professor Ingo Ebersberger from Goethe University Frankfurt/LOEWE Center for Translational Biodiversity Genomics (LOEWE-TBG) has now reached a milestone in this understanding. The team consists 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 took advantage of the fact that a large proportion of the members of the acinetobacter genus are harmless environmental bacteria that live in water or on plants or animals. Thousands of complete genome sequences, both from these and from pathogenic ones acinetobacter tribes are stored in publicly accessible databases.

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

One of the most important properties of pathogens is their ability to form protective biofilms and to efficiently absorb micronutrients such as iron and zinc. And indeed, the researchers found that the recording systems in the ACB group were a reinforcement of the existing and evolutionary older recording mechanism.

Particularly exciting is the fact that the pathogens apparently tapped into a special energy source: they can break down the human-produced carbohydrate kynurenine, which regulates the innate immune system as a messenger. The bacterium apparently kills two birds with one stone in this way. On the one hand, breaking down kynurenine provides them with energy, on the other hand they could potentially use it to deregulate the host’s immune response.

Our work is a milestone in understanding what is different about pathogenic Acinetobacter baumannii. Our data is of such high resolution that we can even look at the situation in individual strains. With this knowledge, specific therapies can now be developed to which there is in all likelihood no resistance yet.†

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