ArticleJournal of bacteriology2014
Accumulation of phosphatidic acid increases vancomycin resistance in Escherichia coli.
Article in Journal of bacteriology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed.
- Unique Regulation of Sed-1 β-Lactamase inAntibiotics (Basel, Switzerland) · 2025Article
- Genetic and virulence factors behind the success of high-riskFrontiers in microbiology · 2025Article
- Biocide-resistant Pseudomonas oleovorans isolated from water-based coatings used in construction.Journal of industrial microbiology & biotechnology · 2024Article
- Thanatin: A Promising Antimicrobial Peptide Targeting the Achilles' Heel of Multidrug-Resistant Bacteria.International journal of molecular sciences · 2024Review
- Effects of pleiotropicJournal of bacteriology · 2024Article
- Vancomycin drug resistance, an emerging threat to animal and public health.Frontiers in veterinary science · 2022Review
- Cardiolipin aids in lipopolysaccharide transport to the gram-negative outer membrane.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Defects in The First Step of Lipoprotein Maturation Underlie The Synthetic Lethality ofJournal of bacteriology · 2021Article
- Multiple Mechanisms of the Synthesized Antimicrobial Peptide TS against Gram-Negative Bacteria for High Efficacy Antibacterial Action In Vivo.Molecules (Basel, Switzerland) · 2020Article
- 2-Aminobenzothiazoles Inhibit Virulence Gene Expression and Block Polymyxin Resistance in Salmonella enterica.Chembiochem : a European journal of chemical biology · 2020Article
- The lipopolysaccharide transport (Lpt) machinery: A nonconventional transporter for lipopolysaccharide assembly at the outer membrane of Gram-negative bacteria.The Journal of biological chemistry · 2017Review
- Identification of unique cardiolipin and monolysocardiolipin species in Acinetobacter baumannii.Scientific reports · 2017Article
- Streptococcus mitis and S. oralis Lack a Requirement for CdsA, the Enzyme Required for Synthesis of Major Membrane Phospholipids in Bacteria.Antimicrobial agents and chemotherapy · 2017Article
- Perturbations of Phosphatidate Cytidylyltransferase (CdsA) Mediate Daptomycin Resistance in Streptococcus mitis/oralis by a Novel Mechanism.Antimicrobial agents and chemotherapy · 2017Article
- Malic enzyme tracers reveal hypoxia-induced switch in adipocyte NADPH pathway usage.Nature chemical biology · 2016Article
- Article
- Loss of membrane-bound lytic transglycosylases increases outer membrane permeability and β-lactam sensitivity in Pseudomonas aeruginosa.MicrobiologyOpen · 2015Article
- Emerging roles for anionic non-bilayer phospholipids in fortifying the outer membrane permeability barrier.Journal of bacteriology · 2014Article
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3 authors.
Funding
Abstract
In Gram-negative bacteria, lipopolysaccharide (LPS) contributes to the robust permeability barrier of the outer membrane, preventing entry of toxic molecules such as antibiotics. Mutations in lptD, the beta-barrel component of the LPS transport and assembly machinery, compromise LPS assembly and result in increased antibiotic sensitivity. Here, we report rare vancomycin-resistant suppressors that improve barrier function of a subset of lptD mutations. We find that all seven suppressors analyzed mapped to the essential gene cdsA, which is responsible for the conversion of phosphatidic acid to CDP-diacylglycerol in phospholipid biosynthesis. These cdsA mutations cause a partial loss of function and, as expected, accumulate phosphatidic acid. We show that this suppression is not confined to mutations that cause defects in outer membrane biogenesis but rather that these cdsA mutations confer a general increase in vancomycin resistance, even in a wild-type cell. We use genetics and quadrupole time of flight (Q-TOF) liquid chromatography-mass spectrometry (LC-MS) to show that accumulation of phosphatidic acid by means other than cdsA mutations also increases resistance to vancomycin. We suggest that increased levels of phosphatidic acid change the physical properties of the outer membrane to impede entry of vancomycin into the periplasm, hindering access to its target, an intermediate required for the synthesis of the peptidoglycan cell wall.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.