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Biosensor for Detection of Antibiotic Resistant Staphylococcus Bacteria
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Thermosensitive PBP2a requires extracellular folding factors PrsA and HtrA1 for Staphylococcus aureus MRSA β-lactam

Mélanie Roch1, Emmanuelle Lelong2, Olesya O Panasenko1,2

  • 11Department of Microbiology and Molecular Medicine, University Hospital and Medical School of Geneva, 1 rue Michel-Servet, Geneva, CH-1211 Switzerland.

Communications Biology
|November 23, 2019
PubMed

Insights

Disrupting chaperone proteins PrsA and HtrA1 severely hinders the folding of PBP2a, a key factor in methicillin-resistant Staphylococcus aureus (MRSA) antibiotic resistance. This approach restores sensitivity to beta-lactam antibiotics like oxacillin.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Drug Discovery

Background:

  • Staphylococcus aureus is a significant human pathogen.
  • Antibiotic resistance, particularly from methicillin-resistant Staphylococcus aureus (MRSA), poses a major clinical challenge.
  • MRSA resistance stems from the mecA gene, encoding PBP2a, which confers resistance to beta-lactam antibiotics.

Purpose of the Study:

  • To investigate the role of chaperone proteins PrsA and HtrA1 in the folding and function of PBP2a.
  • To explore the potential of targeting the PBP2a folding pathway as an adjuvant strategy against MRSA.

Main Methods:

  • Genetic disruption of PrsA and HtrA1 in MRSA.
  • Biochemical analysis of PBP2a folding, unfolding, and activity.
  • Testing the restored sensitivity to beta-lactam antibiotics.

Main Results:

  • Dual disruption of PrsA and HtrA1 synergistically attenuated PBP2a folding.
  • Purified PBP2a exhibits unfolding and precipitation at physiological temperatures.
  • The disruption restored MRSA sensitivity to oxacillin.

Conclusions:

  • Extracellular protein folding factors are essential for MRSA beta-lactam resistance.
  • Targeting the PBP2a folding pathway is a promising strategy to combat antibiotic resistance.
Keywords:
Bacterial genesChaperones

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