Antibiotics: Is a solution of the resistance problem in sight?

A look at the targeted elimination of virulence factors in pathogenic germs

Antibiotic resistance is a serious problem worldwide. Overuse, misuse and also the almost exponential use of antibiotics in animal production have all contributed to this development. In the near future, important medications may no longer be usable. The search for alternatives to antibiotics has therefore long ago begun.

The situation of increasing antibiotic resistance is further exacerbated by the fact that new antibiotics are difficult to develop. This requires completely new substance classes, and for decades pharmaceutical companies and medical practitioners have relied on the currently available preparations and their derivatives. Estimates currently assume that more and more people will die of multi-resistant germs in the coming years due to the serious resistance situation.

"This makes it all the more important that we are now also researching alternatives to antibiotics, which at best should not cause any resistance of their own," said Dr. Giuseppe Magistro, a urologist from Munich at this year's EAU Congress in Barcelona.  Magistro and his colleagues are currently working on a multi-epitope vaccine and on adhesion-inhibiting substances to prevent biofilm formation and thus, for example, recurring UTIs.

An important virulence factor for uropathogenic Escherichia coli (E. coli) is the Yersiniabactin (Ybt) system. The related membrane receptor FyuA also plays an important role in biofilm formation. The formation of biofilms in E. coli is supported by the iron-absorbing receptor IroN of the so-called Salmochelin system.

Magistro and colleagues developed suitable inhibitors against these multifunctional iron uptake receptors in E. coli. The results showed that the blocking peptides used inhibited 80% of biofilm formation in vitro in both E. coli and Klebsiella pneumoniae.

In a second subproject, Magistro and colleagues tested a self-derived multi-epitope vaccine against iron-absorbing receptors in E. coli in a mouse model. The application is either done with a nano-needle to trigger the strongest possible T-cell response or with a nasal spray to strengthen the humoral immune response. For both approaches, the researchers demonstrated a strong protective effect against E. coli used in the mouse model.  

With the new approach of directly attacking the virulence factors of pathogenic bacteria, it could also be possible in the future to treat infectious diseases that have become untreatable. The use of blocking peptides, directly or in the form of a vaccine, also offers the possibility of being able to treat independently of the resistance situation. The first in vitro and in vivo experiments have so far been very promising. However, it will probably be years before the new treatment approach is available and will, of course, depend in particular on the approval of further funding.

Source: P290: Magistro G et al., Anti-virulence treatment: The solution to antimicrobial resistance? EAU 2019, Barcelona

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