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Daptomycin-Mediated Reorganization of Membrane Architecture Causes Mislocalization of Essential Cell Division Proteins

Journal of Bacteriology, 2012-09, Vol.194 (17), p.4494-4504 [Peer Reviewed Journal]

2015 INIST-CNRS ;Copyright American Society for Microbiology Sep 2012 ;Copyright © 2012, American Society for Microbiology. All Rights Reserved. 2012 American Society for Microbiology ;ISSN: 0021-9193 ;EISSN: 1098-5530 ;EISSN: 1067-8832 ;DOI: 10.1128/JB.00011-12 ;PMID: 22661688 ;CODEN: JOBAAY

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Title:
Daptomycin-Mediated Reorganization of Membrane Architecture Causes Mislocalization of Essential Cell Division Proteins
Author: Pogliano, Joe ; Pogliano, Nicolas ; Silverman, Jared A
Subjects: Anti-Bacterial Agents - pharmacology ; antibiotic resistance ; Antibiotics ; Bacillus subtilis ; Bacillus subtilis - drug effects ; Bacillus subtilis - metabolism ; Bacillus subtilis - ultrastructure ; Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; Bacteriology ; biogenesis ; Biological and medical sciences ; Cell Cycle Proteins - metabolism ; cell death ; Cell Division ; Cell Membrane - drug effects ; Cell Membrane - metabolism ; Cell Membrane - ultrastructure ; cell membranes ; Cell Wall - drug effects ; Cell Wall - enzymology ; cell walls ; daptomycin ; Daptomycin - metabolism ; Daptomycin - pharmacology ; enzymes ; fluorescence ; fluorescence microscopy ; Fundamental and applied biological sciences. Psychology ; Gram-positive bacteria ; lipopeptides ; mechanism of action ; methicillin ; Microbial Sensitivity Tests ; Microbiology ; Microscopy, Fluorescence ; Miscellaneous ; Peptides ; Peptidoglycan - biosynthesis ; peptidoglycans ; Proteins ; Staphylococcus aureus ; Staphylococcus infections
Is Part Of: Journal of Bacteriology, 2012-09, Vol.194 (17), p.4494-4504
Description: Daptomycin is a lipopeptide antibiotic used clinically for the treatment of certain types of Gram-positive infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). Details of the mechanism of action of daptomycin continue to be elucidated, particularly the question of whether daptomycin acts on the cell membrane, the cell wall, or both. Here, we use fluorescence microscopy to directly visualize the interaction of daptomycin with the model Gram-positive bacterium Bacillus subtilis. We show that the first observable cellular effects are the formation of membrane distortions (patches of membrane) that precede cell death by more than 30 min. Membrane patches are able to recruit the essential cell division protein DivIVA. Recruitment of DivIVA correlates with membrane defects and changes in cell morphology, suggesting a localized alteration in the activity of enzymes involved in cell wall synthesis that could account for previously described effects of daptomycin on cell wall morphology and septation. Membrane defects colocalize with fluorescently labeled daptomycin, DivIVA, and fluorescent reporters of peptidoglycan biogenesis (Bocillin FL and BODIPY FL-vancomycin), suggesting that daptomycin plays a direct role in these events. Our results support a mechanism for daptomycin with a primary effect on cell membranes that in turn redirects the localization of proteins involved in cell division and cell wall synthesis, causing dramatic cell wall and membrane defects, which may ultimately lead to a breach in the cell membrane and cell death. These results help resolve the longstanding questions regarding the mechanism of action of this important class of antibiotics.
Publisher: Washington, DC: American Society for Microbiology
Language: English
Identifier: ISSN: 0021-9193
EISSN: 1098-5530
EISSN: 1067-8832
DOI: 10.1128/JB.00011-12
PMID: 22661688
CODEN: JOBAAY
Source: GFMER Free Medical Journals
MEDLINE
PubMed Central

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Daptomycin-Mediated Reorganization of Membrane Architecture Causes Mislocalization of Essential Cell Division Proteins

2015 INIST-CNRS ;Copyright American Society for Microbiology Sep 2012 ;Copyright © 2012, American Society for Microbiology. All Rights Reserved. 2012 American Society for Microbiology ;ISSN: 0021-9193 ;EISSN: 1098-5530 ;EISSN: 1067-8832 ;DOI: 10.1128/JB.00011-12 ;PMID: 22661688 ;CODEN: JOBAAY

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