Renew or die: The molecular mechanisms of peptidoglycan recycling and antibiotic resistance in Gram-negative pathogens.
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.
Department of Crystallography and Structural Biology, Inst. Química-Física "Rocasolano", CSIC, Serrano 119, 28006 Madrid, Spain.
Teresa
T
Domínguez-Gil
Department of Crystallography and Structural Biology, Inst. Química-Física "Rocasolano", CSIC, Serrano 119, 28006 Madrid, Spain.
Rafael
R
Molina
Department of Crystallography and Structural Biology, Inst. Química-Física "Rocasolano", CSIC, Serrano 119, 28006 Madrid, Spain.
Martín
M
Alcorlo
Department of Crystallography and Structural Biology, Inst. Química-Física "Rocasolano", CSIC, Serrano 119, 28006 Madrid, Spain. Electronic address: xjuan@iqfr.csic.es.
Juan A
JA
Hermoso
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001692:Biological Transport; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006596:Hexosaminidases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D010457:Peptidoglycan / Q000378:metabolism*; D046928:Peptidoglycan Glycosyltransferase / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D010457:Peptidoglycan; D046928:Peptidoglycan Glycosyltransferase; D006596:Hexosaminidases; D001618:beta-Lactamases
Antibiotic resistance; Cell-wall recycling; Gram-negative bacteria; Lytic transglycosylases; Peptidoglycan amidases; Structural biology