Abcf atpases in antibiotic resistance and regulation of bacterial translation

0581909 - MBÚ 2024 RIV CZ eng A - Abstract
Koběrská, Markéta - Mahor, Durga - Demay, Fanny - Novotná, Michaela - Omena Petravicius, Pamela - Kameník, Zdeněk - Janata, Jiří - Balíková Novotná, Gabriela
Abcf atpases in antibiotic resistance and regulation of bacterial translation.
Czech Chem. Soc. Symp. Series. Roč. 21, č. 5 (2023), s. 211-211
[Annual meeting of the National Institute of Virology and Bacteriology (NIVB) /2./. 02.10.2023-05.10.2023, Kutná Hora]
R&D Projects: GA MŠMT(CZ) LX22NPO5103
Institutional support: RVO:61388971
Keywords : Antibiotic resistance * ATP-binding * ABCF protein * proteins
OECD category: Microbiology

Antibiotic resistance is a serious public health problem, complicating the treatment of infectious diseases and reducing the effectiveness of therapeutic interventions. To address this threat, efforts are underway to develop new antibiotics that are effective against resistant strains. However, the efficacy of new agents may be compromised by emerging or insufficiently explored resistance mechanisms.
The ATP-binding cassette transporters (ABC) of the F family (ABCF) form a group of poorly studied cytosolic proteins that interact with the ribosome. A substantial fraction of these proteins confer resistance to antibiotics that bind to the large subunit of the bacterial ribosome1. These proteins are called antibiotic resistance elements (ARE). Their expression is triggered by the presence of antibiotics bound to the large subunit of the ribosome2–4, and they protect the ribosome by displacing the bound antibiotics5. The antibiotic displacement catalyzed by the ARE ABCF proteins leads not only to antibiotic resistance, but it can also regulate gene expression. This ability we have demonstrated in variants of the resistance protein VgaA in Staphylococcus aureus, which fine-tunes its own expression depending on whether it confers resistance to a particular antibiotic from the group of lincosamides, streptogramins A, and pleuromutilins (LSaP)2. However, our main discovery is the antibiotic signaling function of the ARE5 ABCF protein, LmrC, from the soil bacterium Streptomyces lincolnensis. LmrC is encoded within the biosynthetic gene cluster for lincomycin (BGC). It responds to the presence of lincosamides by synchronizing lincomycin production by activating transcription of the transcriptional regulator gene lmbU4. The ABCF family proteins comprise.
Permanent Link: https://hdl.handle.net/11104/0350056