Modulating Isoprenoid Biosynthesis Increases Lipooligosaccharides and Restores Acinetobacter baumannii Resistance to Host and Antibiotic Stress

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved..

Acinetobacter baumannii is a leading cause of ventilator-associated pneumonia and a critical threat due to multidrug resistance. The A. baumannii outer membrane is an asymmetric lipid bilayer composed of inner leaflet glycerophospholipids and outer leaflet lipooligosaccharides. Deleting mlaF of the maintenance of lipid asymmetry (Mla) system causes A. baumannii to become more susceptible to pulmonary surfactants and antibiotics and decreases bacterial survival in the lungs of mice. Spontaneous suppressor mutants isolated from infected mice contain an ISAba11 insertion upstream of the ispB initiation codon, an essential isoprenoid biosynthesis gene. The insertion restores antimicrobial resistance and virulence to ΔmlaF. The suppressor strain increases lipooligosaccharides, suggesting that the mechanism involves balancing the glycerophospholipids/lipooligosaccharides ratio on the bacterial surface. An identical insertion exists in an extensively drug-resistant A. baumannii isolate, demonstrating its clinical relevance. These data show that the stresses bacteria encounter during infection select for genomic rearrangements that increase resistance to antimicrobials.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:32

Enthalten in:

Cell reports - 32(2020), 10 vom: 08. Sept., Seite 108129

Sprache:

Englisch

Beteiligte Personen:

Palmer, Lauren D [VerfasserIn]
Minor, Keaton E [VerfasserIn]
Mettlach, Joshua A [VerfasserIn]
Rivera, Emilio S [VerfasserIn]
Boyd, Kelli L [VerfasserIn]
Caprioli, Richard M [VerfasserIn]
Spraggins, Jeffrey M [VerfasserIn]
Dalebroux, Zachary D [VerfasserIn]
Skaar, Eric P [VerfasserIn]

Links:

Volltext

Themen:

Acinetobacter
Anti-Bacterial Agents
Antibiotic resistance
Isoprenoid
Journal Article
Lipid-linked oligosaccharides
Lipooligosaccharides
Lipopolysaccharides
Mla
Outer membrane
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Terpenes

Anmerkungen:

Date Completed 28.05.2021

Date Revised 11.02.2024

published: Print

Citation Status MEDLINE

doi:

10.1016/j.celrep.2020.108129

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM314783741