Bacteria are able to detect very low levels of antibiotics and activate defensive responses

Scientists from the Institute of Microbiology, the Institute of Biotechnology, and the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences have described a mechanism by which bacteria can “sense” even very low amounts of antibiotics in their environment and trigger a defensive response. This discovery highlights a little-studied aspect of antibiotic resistance and opens up new possibilities for more accurate diagnosis and the development of new antibiotics.

Bacterial RNA polymerase (RNAP) is the key enzyme in bacterial transcription. Its interaction partner, the HelD protein, protects it from the antibiotic rifampicin (RIF). Bacteria sense the presence of RIF at the level of transcription of the helD gene from DNA to mRNA, which is then used as a template for the translation of the HelD protein. This transcription is induced by very low concentrations of RIF and is controlled by the mutual interaction of RNA polymerases, which initiate transcription from two opposing (convergent) promoters (sequences in DNA where transcription begins) – PhelD initiates transcription of the helD gene, and Panti-helD in the opposite direction has a regulatory role.

In the absence of RIF, strong transcription from Panti-helD dominates, allowing only sporadic transcription from PhelD (RNAP leaves this promoter more slowly). In the presence of RIF, however, the situation is reversed: RNAP has enough time to leave PhelD because RNAP bound to Panti-helD is stopped by rifampicin and cannot interfere with initiation of transcription from PhelD. This leads to transcription (and subsequent translation) of the helD gene and increased resistance of the bacterium to this antibiotic. The illustration metaphorically captures this regulation where RNA polymerases are depicted as locomotives and DNA as railroad tracks. These results have made it possible to also identify a similar mechanism, for example controlling the pps gene, which encodes a protein that inactivates rifampicin through modification.

This study thus reveals a previously unknown strategy in the bacterial arsenal against the antibiotic rifampicin. In the future, when it will be possible to routinely determine the DNA sequence of infectious bacteria in specific patients, this knowledge may then help in diagnosis or the design of treatment regimens.

Link to publication: HERE

Bacteria sense the antibiotic rifampicin through a widespread dual-promoter based alarm system (2026) Sudzinová, P, Knežová Balgová, T, Schwarz, M, Juříková Mikesková, K, Hegrová, K, Vítovská, K, Rawat, K , Bobková, Š, Kočárková, V, Natarajan, S, Pospíšilová, D, Křenková, A, Hubálek, M, Halada, P, Barvík, I, Koval, T, Dohnálek, J, Wiedermannová, J, Šanderová, H, Krásný, L. Nucleic Acids Res (in press) doi: 10.1093/nar/gkaf1407