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Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
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Occurrence and mechanisms of glycopeptide resistance in gram-positive cocci

V Saha1, S Gupta, R S Daum

  • 1Section of Pediatric Infectious Diseases, Wyler Children's Hospital, University of Chicago, Illinois 60637.

Infectious Agents and Disease
|December 1, 1992
PubMed

Insights

Glycopeptide resistance in enterococci and staphylococci is a growing concern. Understanding the mechanisms of resistance is crucial for effective treatment strategies against these Gram-positive bacteria.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Infectious Diseases

Background:

  • Glycopeptides were once thought to be immune to resistance development due to their unique mechanism of action.
  • However, clinical isolates of enterococci and staphylococci exhibiting resistance to glycopeptides have emerged.
  • This necessitates a re-evaluation of susceptibility assumptions for these critical pathogens.

Purpose of the Study:

  • To investigate and describe the mechanisms of glycopeptide resistance in clinically significant enterococci and staphylococci.
  • To highlight the diversity of resistance types within enterococcal species.
  • To characterize novel resistance mechanisms observed in staphylococci.

Main Methods:

  • Characterization of enzymatic activities (ligase, dehydrogenase, carboxypeptidase) involved in peptidoglycan precursor synthesis.
  • Induction studies to assess the role of enzymes in resistance.
  • Genetic analysis to identify chromosomal or inducible resistance determinants.
  • Proteomic analysis to identify novel proteins associated with resistance.
  • Laboratory-induced resistance studies in staphylococci.

Main Results:

  • Enterococci exhibit at least three distinct resistance types (A, B, and C) mediated by altered enzyme activity or novel protein production.
  • Type A resistance involves inducible enzymes affecting peptidoglycan precursors.
  • Type C resistance in E. gallinarum is linked to a constitutively produced, chromosomally encoded ligase.
  • Staphylococcal resistance mechanisms, including a 39-kDa protein and cell surface reorganization, are still under investigation.

Conclusions:

  • The era of presumed universal Gram-positive susceptibility to glycopeptides is over.
  • Distinct molecular mechanisms underlie glycopeptide resistance in enterococci and staphylococci.
  • Routine susceptibility testing is now essential for clinical isolates of enterococci and staphylococci.

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