ArticleMicrobiologyOpen2015
Loss of membrane-bound lytic transglycosylases increases outer membrane permeability and β-lactam sensitivity in Pseudomonas aeruginosa.
Article in MicrobiologyOpen, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 67 citations in OpenAlex.
- Outer Membrane-Peptidoglycan Anchoring inJournal of the American Chemical Society · 2026Article
- Prevalence and mechanisms of high-level carbapenem antibiotic tolerance in clinical isolates of Klebsiella pneumoniae.PLoS pathogens · 2026Article
- Evolution of Resistant Mutants inMicroorganisms · 2025Article
- Article
- Bacterial peptidoglycan as a living polymer.Current opinion in chemical biology · 2025Review
- Article
- Lytic transglycosylase repertoire diversity enables intrinsic antibiotic resistance and daughter cell separation inAntimicrobial agents and chemotherapy · 2024Article
- Lytic transglycosylase Slt of Pseudomonas aeruginosa as a periplasmic hub protein.Protein science : a publication of the Protein Society · 2024Article
- Structural characterization of lytic transglycosylase MltD of Pseudomonas aeruginosa, a target for the natural product bulgecin A.International journal of biological macromolecules · 2024Article
- Amber-codon suppression for spatial localization and in vivo photoaffinity capture of the interactome of the Pseudomonas aeruginosa rare lipoprotein A lytic transglycosylase.Protein science : a publication of the Protein Society · 2023Article
- Article
- In vitro studies of the protein-interaction network of cell-wall lytic transglycosylase RlpA of Pseudomonas aeruginosa.Communications biology · 2022Article
- Genomic Epidemiology of Vibrio cholerae O139, Zhejiang Province, China, 1994-2018.Emerging infectious diseases · 2022Article
- Induction of AmpC-Mediated β-Lactam Resistance Requires a Single Lytic Transglycosylase in Agrobacterium tumefaciens.Applied and environmental microbiology · 2022Article
- Rapid expansion and extinction of antibiotic resistance mutations during treatment of acute bacterial respiratory infections.Nature communications · 2022Article
- Spectinomycin resistance inFrontiers in microbiology · 2022Article
- β-lactam Resistance inPathogens (Basel, Switzerland) · 2021Review
- Biofilm Formation byApplied and environmental microbiology · 2021Article
- Transmission, adaptation and geographical spread of theMicrobial genomics · 2021Article
- Diversification of LytM Protein Functions in Polar Elongation and Cell Division ofFrontiers in microbiology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The opportunistic pathogen Pseudomonas aeruginosa is a leading cause of nosocomial infections. Its relatively impermeable outer membrane (OM) limits antibiotic entry, and a chromosomally encoded AmpC β-lactamase inactivates β-lactam antibiotics. AmpC expression is linked to peptidoglycan (PG) recycling, and soluble (sLT) or membrane-bound (mLT) lytic transglycosylases are responsible for generating the anhydromuropeptides that induce AmpC expression. Thus, inhibition of LT activity could reduce AmpC-mediated β-lactam resistance in P. aeruginosa. Here, we characterized single and combination LT mutants. Strains lacking SltB1 or MltB had increased β-lactam minimum inhibitory concentrations (MICs) compared to wild type, while only loss of Slt decreased MICs. An sltB1 mltB double mutant had elevated β-lactam MICs compared to either the sltB1 or mltB single mutants (96 vs. 32 μg/mL cefotaxime), without changes to AmpC levels. Time-kill assays with β-lactams suggested that increased MIC correlated with a slower rate of autolysis in the sltB1 mltB mutant - an antisuicide phenotype. Strains lacking multiple mLTs were more sensitive to β-lactams and up to 16-fold more sensitive to vancomycin, normally incapable of crossing the OM. Multi-mLT mutants were also sensitive to bile salts and osmotic stress, and were hyperbiofilm formers, all phenotypes consistent with cell envelope compromise. Complementation with genes encoding inactive forms of the enzymes - or alternatively, overexpression of Braun's lipoprotein - reversed the mutants' cell envelope damage phenotypes, suggesting that mLTs help to stabilize the OM. We conclude that P. aeruginosa mLTs contribute physically to cell envelope stability, and that Slt is the preferred target for future development of LT inhibitors that could synergize with β-lactams.
Indexed as
Identifiers
What OpenQuestion holds
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.