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<p><i>Acinetobacter baumannii</i> emerges as one of the most worrisome pathogens causing a majority of hospital-acquired infections worldwide. However, the knowledge of its virulence factors remains obscure, in particular the bacterial lipooligosaccharides (LOS). Lipid A of the bacterial LOS exists as an inseparable mixture&#xa0;of homologues, making it impossible to study the immunological activity of each component. We herein report the synthesis of <i>A. baumannii</i> lipid A(s) (1−4) and corresponding monophosphate derivatives (1′, 3′ and 4′). The synthetic scheme features a short and stereoselective preparation of <i>β</i>-hydroxy acids and a convergent assembly of lipid A species with diverse structures. Subsequent immunological studies indicate that <i>A. baumannii</i> lipid A (2) having a [4 + 2]-acylation pattern displays the highest stimulatory potency. Further computational studies suggest that 2 and <i>E. coli</i> lipid A (5) sharing the same acylation pattern adopt an inverted binding mode in the TLR4/MD-2 receptor complex.</p><p></p>

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Synthesis of Acinetobacter baumannii Lipid A(s) and derivatives and their structure-immunostimulatory activity relationships

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月6日

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  • Xin-Ru Li,
  • Janet Jia-Yin Tan,
  • Chiao-Wen Chen,
  • Jhen-Yan Huang,
  • Hsien-Ya Lin,
  • Boon Hee Goh,
  • Keng-Chang Tsai,
  • Chun-Hung Lin,
  • Kwok-Kong Tony Mong

摘要

Acinetobacter baumannii emerges as one of the most worrisome pathogens causing a majority of hospital-acquired infections worldwide. However, the knowledge of its virulence factors remains obscure, in particular the bacterial lipooligosaccharides (LOS). Lipid A of the bacterial LOS exists as an inseparable mixture of homologues, making it impossible to study the immunological activity of each component. We herein report the synthesis of A. baumannii lipid A(s) (1−4) and corresponding monophosphate derivatives (1′, 3′ and 4′). The synthetic scheme features a short and stereoselective preparation of β-hydroxy acids and a convergent assembly of lipid A species with diverse structures. Subsequent immunological studies indicate that A. baumannii lipid A (2) having a [4 + 2]-acylation pattern displays the highest stimulatory potency. Further computational studies suggest that 2 and E. coli lipid A (5) sharing the same acylation pattern adopt an inverted binding mode in the TLR4/MD-2 receptor complex.