TY - JOUR
T1 - Renew or die
T2 - The molecular mechanisms of peptidoglycan recycling and antibiotic resistance in Gram-negative pathogens
AU - Domínguez-Gil, Teresa
AU - Molina, Rafael
AU - Alcorlo, Martín
AU - Hermoso, Juan A
N1 - Copyright © 2016. Published by Elsevier Ltd.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
KW - Anti-Bacterial Agents/pharmacology
KW - Biological Transport
KW - Cell Wall/chemistry
KW - Drug Resistance, Multiple, Bacterial/genetics
KW - Gene Expression Regulation, Bacterial
KW - Gram-Negative Bacteria/drug effects
KW - Gram-Negative Bacterial Infections/drug therapy
KW - Hexosaminidases/genetics
KW - Humans
KW - Models, Molecular
KW - Peptidoglycan/metabolism
KW - Peptidoglycan Glycosyltransferase/chemistry
KW - Protein Domains
KW - Protein Structure, Secondary
KW - beta-Lactamases/genetics
U2 - 10.1016/j.drup.2016.07.002
DO - 10.1016/j.drup.2016.07.002
M3 - Review
C2 - 27620957
SN - 1368-7646
VL - 28
SP - 91
EP - 104
JO - Drug Resistance Updates
JF - Drug Resistance Updates
ER -