title: Lipopolysaccharide-deficient Acinetobacter baumannii shows altered signaling through host Toll-like receptors and increased susceptibility to the host antimicrobial peptide LL-37.
abstract: Infections caused by multidrug-resistant Acinetobacter baumannii have emerged as a serious global health problem. We have shown previously that A. baumannii can become resistant to the last-line antibiotic colistin via the loss of lipopolysaccharide (LPS), including the lipid A anchor, from the outer membrane (J. H. Moffatt, M. Harper, P. Harrison, J. D. Hale, E. Vinogradov, T. Seemann, R. Henry, B. Crane, F. St. Michael, A. D. Cox, B. Adler, R. L. Nation, J. Li, and J. D. Boyce, Antimicrob. Agents Chemother. 54:4971-4977, 2010). Here, we show how these LPS-deficient bacteria interact with components of the host innate immune system. LPS-deficient A. baumannii stimulated 2- to 4-fold lower levels of NF-κB activation and tumor necrosis factor alpha (TNF-α) secretion from immortalized murine macrophages, but it still elicited low levels of TNF-α secretion via a Toll-like receptor 2-dependent mechanism. Furthermore, we show that while LPS-deficient A. baumannii was not altered in its resistance to human serum, it showed increased susceptibility to the human antimicrobial peptide LL-37. Thus, LPS-deficient, colistin-resistant A. baumannii shows significantly altered activation of the host innate immune inflammatory response.
authors.affiliation: Department of Microbiology, Monash University, Victoria, Australia.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Moffatt
authors.forename: Marina
authors.initials: M
authors.lastname: Harper
authors.forename: Ashley
authors.initials: A
authors.lastname: Mansell
authors.forename: Bethany
authors.initials: B
authors.lastname: Crane
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Fitzsimons
authors.forename: Roger L
authors.initials: RL
authors.lastname: Nation
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Ben
authors.initials: B
authors.lastname: Adler
authors.forename: John D
authors.initials: JD
authors.lastname: Boyce
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects*; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha