Abcf atpases in antibiotic resistance and regulation of bacterial translation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F23%3A00581909" target="_blank" >RIV/61388971:_____/23:00581909 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Abcf atpases in antibiotic resistance and regulation of bacterial translation

Popis výsledku v původním jazyce

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.nThe 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.

Název v anglickém jazyce

Abcf atpases in antibiotic resistance and regulation of bacterial translation

Popis výsledku anglicky

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.nThe 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.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10606 - Microbiology

Projekt

<a href="/cs/project/LX22NPO5103" target="_blank" >LX22NPO5103: Národní institut virologie a bakteriologie</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů