A previously unknown mechanism allows bacterial antibiotic resistance, Researchers have described previously unknown mechanisms to regulate bacterial transcription that appear to be widespread in bacteria.

The findings can also help in the fight against antibiotic resistance in the future.

Bacteria are often exposed to various types of changes in their environment. To survive stress or changing conditions, bacteria must respond quickly and appropriately to achieve a physiologically responsive response. This is mainly due to the specific adaptation of gene expression. previously unknown mechanism allows bacterial antibiotic resistance.

This makes transcription regulation one of the best ways to adapt bacteria to external stress conditions.

Transcription of bacteria begins only after the key component, known as the sigma factor (factor σ), has been bound to the main RNA polymerase enzyme (RNAP) to form a complete and catalytically active holoenzim. . This holoenzyme then recognizes important promoter elements and then activates transcription.

In the case of external pressures, the main factor σ is replaced by an alternative factor σ, which differs from the first in terms of the recognized promoter sequence. The formation of holoenzyme by this alternative σ factor leads to the transcription of the appropriate stress response gene. Among the various classes of alternative σ factors, the most common are the extracitoplasmic (ECF) factors. now the previously unknown mechanism allows bacterial antibiotic resistance.

The sigma factor is usually naturally active, which means that the bacterial cell must remain inactive until the effect is justified.

There are various mechanisms to regulate factor activity σ. Usually, alternatives & sgr; Factors in the inactive state by absorption in complexes with anti? Factor saved.

With a specific stimulus, the inhibitory effect of the anti-σ factor weakens and the σ factor is released to interact with RNA polymerase.

In collaboration with SYNMIKRO researchers in Marburg, Max Planck researchers have discovered a hitherto unknown mechanism of transcription regulation that is based on inherently inactive σ factors that cannot bind to the main RNAP enzyme.

The σ factor is only activated by specific residual phosphorylation and can bind to RNAP during the formation of holoenzyme and thus trigger specific gene expression.

Comprehensive analysis of bioinformatics has shown that the regulation of transcription by σ-phosphorylation is a common mechanism in bacteria and represents a new paradigm for transcription regulation.

The specialty of this mechanism is its modularity, “explained research group leader Simon Ringgard. Our results show how nature has combined two different mechanisms to regulate threonine kinase signals and factor σ activity as a joint force to achieve the ability to adapt to the environment.

The Ringgaard organism itself is the area of ​​application: Vibrio parahaemolyticus is a serious human pathogen and the main pathogenic gastroenteritis in the sea, which is transmitted by seafood. Max Planck researchers identified the pair of ECF / threonine kinase factors (called EcfP / PknT) which are responsible for the sensitization of polymyxin antibiotics and mediating bacterial resistance to polymyxins on V. parahaemolyticus.

PknT kinase is activated when cells are treated with polymyxin antibiotics. Activated PknT in turn activates EcfP, which leads to the expression of genes needed for antibiotic resistance to polyimixins.

Polymyxins is a class of antibiotics that are considered as a last resort for the treatment of gram negative infections.

Because antibiotic resistance is a serious public health problem throughout the world, it is very important to understand how cells perceive and respond to antibiotic treatments.

The identification of mechanisms that regulate the resistance of polymyxin antibiotics in V. parahaemolyticus opens new opportunities for research in combating this and other possible important human pathogens.

Finally, the work of the Marburg researchers provides fundamental ideas for regulating gene expression and cellular adaptation throughout the bacterial world.