Newly discovered mechanism enables bacterial antibiotic resistance

Researchers from the Max Planck Institute for Terrestrial Microbiology in Marburg have described a previously unrecognized mechanism of bacterial transcriptional regulation that is obviously widespread in bacteria. In the future, their findings could also help fight antibiotic resistance.

Within their environment, bacteria often encounter various kinds of changes. In order to survive under stress or changing conditions, bacteria have to respond fast and adequate to achieve a physiological adaptive response. This mostly happens by specifically adapting gene expression. Thus, transcriptional regulation is one of the biggest means by which bacteria adapt to external stress conditions.

Initiation of transcription in bacteria only occurs upon the binding of a key component known as the sigma factor (σ factor) to the RNA polymerase (RNAP) core enzyme in order to form the complete and catalytically active holoenzyme. This holoenzyme then recognizes key promotor elements and subsequently enables transcription. During external stress conditions, the primary σ factor is replaced by an alternative σ factor, which differs from the former with respect to the promoter sequences that it recognizes. Thus, holoenzyme formation with this alternative σ factor results in the transcription of corresponding stress-response genes. Among the various classes of alternative σ factors, the most abundant ones are the extracytoplasmic function (ECF) σ factors. Sigma factors are commonly known to be intrinsically active, which means that the bacterial cell has to keep them in an inactive state until their action is warranted.

There are several mechanisms for regulating σ factor activity. Usually, alternative σ factors stay retained in an inactive state by sequestration into a complex with an anti-σ factor. Upon a specific stimulus, the inhibitory effect of the anti-σ factor is alleviated and the σ factor is released for interaction with the RNA polymerase.

See:

Shankar Chandrashekar Iyer, Delia Casas-Pastor, David Kraus, Petra Mann, Kathrin Schirner, Timo Glatter, Georg Fritz, Simon Ringgaard. Transcriptional regulation by σ factor phosphorylation in bacteria. Nature Microbiology, 2020; DOI: 10.1038/s41564-019-0648-6

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)