Molecular mechanism of gene expression induced by lincosamide antibiotics targeting the 50S ribosomal subunit

Michaela Novotná1, C. Axel Innis2, Gabriela Balíková Novotná1

1Institute of Microbiology CAS, BIOCEV, Vestec, Czech Republic

2INSERM U1212 (ARNA), Institut Européen de Chimie et Biologie, Université de Bordeaux, Pessac,  France

Bacterial Antibiotic REsistance ABC ATPases F (ARE ABC-F) are cytosolic proteins conferring resistance to 50S ribosomal subunit binding antibiotics via target protection mechanism. Expression of all previously characterised ARE ABC-F genes that confer resistance to peptidyl transferase centre targeting antibiotics lincosamides, streptogramins A and pleuromutilins (LSAP) is regulated by ribosome-mediated attenuation in response to these antibiotics, however the molecular mechanism is lacking.  Considering that antibiotic-driven attenuation generally requires sequence-dependent translational arrest, we would expect the same also for LSAP-driven attenuation. The aim of our research is to shed light on the mechanism of LSAP-induced translation inhibition using ribosome profiling techniques (toeprinting and high-throughput inverse toeprinting) and single particle cryo-EM and based on these data, to clarify the expression regulation of ARE ABC-Fs in pathogens and antibiotic producers.