Lipopolysaccharide-deficient Acinetobacter baumannii shows altered signaling through host Toll-like receptors and increased susceptibility to the host antimicrobial peptide LL-37.
Moffatt. Jennifer H JH; Harper. Marina M; Mansell. Ashley A; Crane. Bethany B; Fitzsimons. Timothy C TC; Nation. Roger L RL; Li. Jian J; Adler. Ben B; Boyce. John D JD
Key Findings
- LPS‑deficient A. baumannii causes 2‑ to 4‑fold lower NF‑κB activation and TNF‑α release from macrophages.
- The reduced response is still partly driven by Toll‑like receptor 2.
- These LPS‑deficient, colistin‑resistant bacteria are not more vulnerable to human serum but are more sensitive to the peptide LL‑37.
Practical Outcomes
- For DIY health enthusiasts, the study mainly adds basic science about how a natural human peptide can target a specific antibiotic‑resistant bug. It does not provide a ready‑to‑use protocol, dosage guidance, or evidence that taking LL‑37 will improve health or protect against infections.
Summary
A strain of the superbug Acinetobacter baumannii that loses its outer membrane coating (LPS) triggers a weaker immune alarm in mouse cells and is easier for the human antimicrobial peptide LL‑37 to kill, although it still resists normal human serum.
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.
Study Information
pubmed
2012
2012-12-17T00:00:00.000Z
10.1128/iai.01362-12