ArticleProceedings of the National Academy of Sciences of the United States of America2016
A penicillin-binding protein inhibits selection of colistin-resistant, lipooligosaccharide-deficient Acinetobacter baumannii.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 144 citations in OpenAlex.
- LPS in gram-negative bacterial growth and physiology: outside but fully integrated.Microbiology and molecular biology reviews : MMBR · 2026Review
- Collateral sensitivity-harnessing microbial vulnerabilities as a solution to antimicrobial resistance.Molecular biology reports · 2026Review
- Outer membrane remodeling via lipid-peptidoglycan crosstalk enables lipooligosaccharide-deficient colistin resistance.Cell reports · 2026Article
- Van der Waals interactions mediate the enantiomeric substrate preference of the CTP:phosphoglycerate cytidylyltransferase CpgD.bioRxiv : the preprint server for biology · 2026Article
- Article
- Combinations of colistin and bacteriocins prevent the selection of colistin resistance in Acinetobacter baumannii.Communications biology · 2026Article
- A surface-exposed cardiolipin synthase provides an unexpected paradigm for maintaining the Gram-negative outer membrane.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Resistance, heteroresistance, and fitness costs drive colistin treatment failure duringProceedings of the National Academy of Sciences of the United States of America · 2026Article
- High-throughput LacZ/CPRG assay for identifying Gram-negative envelope-targeting antibiotics.Frontiers in microbiology · 2026Article
- A conserved hub protein required for peptidoglycan remodeling and cell division inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Resistance, heteroresistance and fitness costs drive colistin treatment failure duringbioRxiv : the preprint server for biology · 2025Article
- Molecular interplay between peptidoglycan integrity and outer membrane asymmetry in maintaining cell envelope homeostasis.Journal of bacteriology · 2025Article
- 2‑Aminoimidazole-benzimidazole Conjugates Potentiate the Gram-Positive Selective Antibiotic Clarithromycin againstACS medicinal chemistry letters · 2025Article
- Inter- and intra-bacterial strain diversity remains the "elephant in the (living) room".npj antimicrobials and resistance · 2025Review
- Chemical genomics informs antibiotic and essential gene function in Acinetobacter baumannii.PLoS genetics · 2025Article
- Natural peptides and their synthetic congeners acting againstRSC medicinal chemistry · 2025Review
- Alternative lipid synthesis in response to phosphate limitation promotes antibiotic tolerance in Gram-negative ESKAPE pathogens.PLoS pathogens · 2025Article
- The BfmRS stress response protectsJournal of bacteriology · 2025Article
- Recent advances in understanding of enterobacterial common antigen synthesis and regulation.Open biology · 2025Review
- Alternative lipid synthesis in response to phosphate limitation promotes antibiotic tolerance in Gram-negative ESKAPE pathogens.bioRxiv : the preprint server for biology · 2024Article
42 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
The Gram-negative bacterial outer membrane fortifies the cell against environmental toxins including antibiotics. Unique glycolipids called lipopolysaccharide/lipooligosaccharide (LPS/LOS) are enriched in the cell-surface monolayer of the outer membrane and promote antimicrobial resistance. Colistin, which targets the lipid A domain of LPS/LOS to lyse the cell, is the last-line treatment for multidrug-resistant Gram-negative infections. Lipid A is essential for the survival of most Gram-negative bacteria, but colistin-resistant Acinetobacter baumannii lacking lipid A were isolated after colistin exposure. Previously, strain ATCC 19606 was the only A. baumannii strain demonstrated to subsist without lipid A. Here, we show that other A. baumannii strains can also survive without lipid A, but some cannot, affording a unique model to study endotoxin essentiality. We assessed the capacity of 15 clinical A. baumannii isolates including 9 recent clinical isolates to develop colistin resistance through inactivation of the lipid A biosynthetic pathway, the products of which assemble the LOS precursor. Our investigation determined that expression of the well-conserved penicillin-binding protein (PBP) 1A, prevented LOS-deficient colony isolation. The glycosyltransferase activity of PBP1A, which aids in the polymerization of the peptidoglycan cell wall, was lethal to LOS-deficient A. baumannii Global transcriptomic analysis of a PBP1A-deficient mutant and four LOS-deficient A. baumannii strains showed a concomitant increase in transcription of lipoproteins and their transporters. Examination of the LOS-deficient A. baumannii cell surface demonstrated that specific lipoproteins were overexpressed and decorated the cell surface, potentially compensating for LOS removal. This work expands our knowledge of lipid A essentiality and elucidates a drug resistance mechanism.
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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.