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Related Concept Videos

Development of Antibiotic Resistance01:30

Development of Antibiotic Resistance

129
Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
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Antibiotic Selection00:57

Antibiotic Selection

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Multiplex PCR Assay for Typing of Staphylococcal Cassette Chromosome Mec Types I to V in Methicillin-resistant Staphylococcus aureus
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Cervimycin-Resistant Staphylococcus aureus Strains Display Vancomycin-Intermediate Resistant Phenotypes.

Alina Dietrich1, Ursula Steffens1, Mike Gajdiss1

  • 1University Hospital Bonngrid.15090.3d, Institute of Medical Microbiology, Immunology and Parasitology, Bonn, Germany.

Microbiology Spectrum
|September 29, 2022
PubMed
Summary
This summary is machine-generated.

Novel antibiotics cervimycin show promise against resistant bacteria. Studies reveal mutations in heat shock and kinase genes confer resistance, leading to vancomycin-intermediate resistance in Staphylococcus aureus.

Keywords:
ClpCClpPDnaKTCSWalK/WalRantibiotic resistancenaphthoquinonevancomycinvancomycin-intermediate resistant S. aureus (VISA)

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Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Antibiotic resistance is a growing global health threat, necessitating new therapeutic strategies.
  • Cervimycins, natural products from Streptomyces tendae, exhibit activity against multidrug-resistant staphylococci and vancomycin-resistant enterococci.
  • Understanding cervimycin's mode of action is crucial for developing novel antibacterial therapies.

Purpose of the Study:

  • To elucidate the mode of action of cervimycin antibiotics.
  • To identify genetic determinants of resistance to cervimycin in Staphylococcus aureus.
  • To investigate the phenotypic consequences of cervimycin resistance.

Main Methods:

  • Generation and characterization of cervimycin-resistant (CmR) Staphylococcus aureus mutants.
  • Whole-genome sequencing to identify mutations in CmR strains.
  • In vitro and in vivo assays to assess protein activity and bacterial resistance.
  • Transcriptomic and proteomic analyses to investigate global gene expression changes.

Main Results:

  • CmR mutants frequently harbored combined mutations in the essential histidine kinase WalK and heat shock genes ClpP, ClpC, or DnaK.
  • Mutations in ClpP or ClpC abolished protease activity, conferring resistance.
  • Mutations in WalK decreased kinase activity and induced a vancomycin-intermediate resistant (VISA) phenotype with altered cell wall structure and growth rate.
  • Massive transcriptomic and proteomic alterations were observed, particularly in heat shock, metal ion homeostasis, and carbohydrate metabolism pathways.

Conclusions:

  • Cervimycin resistance in S. aureus is primarily mediated by mutations in the WalK kinase and the Clp protease system (ClpP/ClpC).
  • Cervimycin resistance is associated with a VISA phenotype, suggesting cervimycin targets cell wall metabolism or the Clp protease system.
  • These findings provide critical insights into cervimycin's mode of action and highlight potential targets for new antibacterial drug development.