Renew or die: The molecular mechanisms of peptidoglycan recycling and antibiotic resistance in Gram-negative pathogens

Teresa Domínguez-Gil, Rafael Molina, Martín Alcorlo, Juan A Hermoso

13 Citations (Scopus)

Abstract

Antimicrobial resistance is one of the most serious health threats. Cell-wall remodeling processes are tightly regulated to warrant bacterial survival and in some cases are directly linked to antibiotic resistance. Remodeling produces cell-wall fragments that are recycled but can also act as messengers for bacterial communication, as effector molecules in immune response and as signaling molecules triggering antibiotic resistance. This review is intended to provide state-of-the-art information about the molecular mechanisms governing this process and gather structural information of the different macromolecular machineries involved in peptidoglycan recycling in Gram-negative bacteria. The growing body of literature on the 3D structures of the corresponding macromolecules reveals an extraordinary complexity. Considering the increasing incidence and widespread emergence of Gram-negative multidrug-resistant pathogens in clinics, structural information on the main actors of the recycling process paves the way for designing novel antibiotics disrupting cellular communication in the recycling-resistance pathway.

Original languageEnglish
JournalDrug Resistance Updates
Volume28
Pages (from-to)91-104
Number of pages14
ISSN1368-7646
DOIs
Publication statusPublished - 1 Sept 2016

Keywords

  • Anti-Bacterial Agents/pharmacology
  • Biological Transport
  • Cell Wall/chemistry
  • Drug Resistance, Multiple, Bacterial/genetics
  • Gene Expression Regulation, Bacterial
  • Gram-Negative Bacteria/drug effects
  • Gram-Negative Bacterial Infections/drug therapy
  • Hexosaminidases/genetics
  • Humans
  • Models, Molecular
  • Peptidoglycan/metabolism
  • Peptidoglycan Glycosyltransferase/chemistry
  • Protein Domains
  • Protein Structure, Secondary
  • beta-Lactamases/genetics

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