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S51 Family Peptidases Provide Resistance to Peptidyl-Nucleotide Antibiotic McC.

ABSTRACT: Microcin C (McC)-like compounds are natural Trojan horse peptide-nucleotide antibiotics produced by diverse bacteria. The ribosomally synthesized peptide parts of these antibiotics are responsible for their facilitated transport into susceptible cells. Once inside the cell, the peptide part is degraded, releasing the toxic payload, an isoaspartyl-nucleotide that inhibits aspartyl-tRNA synthetase, an enzyme essential for protein synthesis. Bacteria that produce microcin C-like compounds have evolved multiple ways to avoid self-intoxication. Here, we describe a new strategy through the action of S51 family peptidases, which we name MccG. MccG cleaves the toxic isoaspartyl-nucleotide, rendering it inactive. While some MccG homologs are encoded by gene clusters responsible for biosynthesis of McC-like compounds, most are encoded by standalone genes whose products may provide a basal level of resistance to peptide-nucleotide antibiotics in phylogenetically distant bacteria. IMPORTANCE Here, we identified a natural substrate for a major phylogenetic clade of poorly characterized S51 family proteases from bacteria. We show that these proteins can contribute to a basal level of resistance to an important class of natural antibiotics.

SUBMITTER: Yagmurov E

PROVIDER: S-EPMC9239234 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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S51 Family Peptidases Provide Resistance to Peptidyl-Nucleotide Antibiotic McC.

Yagmurov Eldar E Gilep Konstantin K Serebryakova Marina M Wolf Yuri I YI Dubiley Svetlana S Severinov Konstantin K

mBio 20220425 3

Microcin C (McC)-like compounds are natural Trojan horse peptide-nucleotide antibiotics produced by diverse bacteria. The ribosomally synthesized peptide parts of these antibiotics are responsible for their facilitated transport into susceptible cells. Once inside the cell, the peptide part is degraded, releasing the toxic payload, an isoaspartyl-nucleotide that inhibits aspartyl-tRNA synthetase, an enzyme essential for protein synthesis. Bacteria that produce microcin C-like compounds have evol ...[more]

PMID: 35467414

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Project description:BackgroundAntimicrobial resistance (AMR) is a major global health issue, bringing significant health burden and costs to societies. Increased antibiotic consumption (ABC) is linked to AMR emergence. Some of the known drivers of ABC are antibiotics over-prescription by physicians and their misuse by patients. Family doctors are recognised as important stakeholders in the control of ABC as they prescribe antibiotics and are considered a reliable source of medical information by patients. Therefore, it is important to explore their perceptions, especially in Romania, which has the highest ABC among European Union Member States. Furthermore, there is no published research exploring Romanian family doctors' perceptions regarding this phenomenon.MethodsThis was a qualitative study with data collection via semi-structured interviews among 12 family doctors. Manifest and latent content analysis was used to gain an in-depth understanding of their perceptions. Findings were mapped onto the domains of the Behaviour Change Wheel to facilitate a theory driven systematization and analysis.ResultsTwo main subthemes emerged: i) factors affecting ABC and prescribing and ii) potential interventions to tackle ABC and antibiotic resistance. The factors were further grouped in those that related to the perceived behaviour of family doctors or patients as well as those that had to do with the various systems, local contexts and the COVID-19 pandemic. An overarching theme: 'family doctors in Romania see their role differently when it comes to antibiotic resistance and perceive the lack of patient education or awareness as one of the major drivers of ABC' was articulated. The main findings suggested that the perceived factors span across the capability, opportunity and motivational domains of the behaviour change wheel and could be addressed through a variety of interventions - some identified by the participants. Findings can also be viewed through cultural lenses which shed further light on the family doctor- patient dynamic when it comes to antibiotics use.ConclusionPotential interventions to tackle identified factors emerged, revolving mostly on efforts to educate patients or the public. This exploratory research provides key perspectives and facilitates further research on potential interventions to successfully address AMR in Romania or similar settings.

Dataset Information

S51 Family Peptidases Provide Resistance to Peptidyl-Nucleotide Antibiotic McC.

Publications

S51 Family Peptidases Provide Resistance to Peptidyl-Nucleotide Antibiotic McC.

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