Structural characterization of the lipid A from the LPS of the haloalkaliphilic bacterium Halomonas pantelleriensis

Abstract

Halomonas pantelleriensis DSM9661(Τ) is a Gram-negative haloalkaliphilic bacterium isolated from the sand of the volcanic Venus mirror lake, closed to seashore in the Pantelleria Island in the south of Italy. It is able to optimally grow in media containing 3-15 % (w/v) total salt and at pH between 9 and 10. To survive in these harsh conditions, the bacterium has developed several strategies that probably concern the bacteria outer membrane, a barrier regulating the exchange with the environment. In such a context, the lipopolysaccharides (LPSs), which are among the major constituent of the Gram-negative outer membrane, are thought to contribute to the restrictive membrane permeability properties. The structure of the lipid A family derived from the LPS of Halomonas pantelleriensis DSM 9661(T) is reported herein. The lipid A was obtained from the purified LPS by mild acid hydrolysis. The lipid A, which contains different numbers of fatty acids residues, and its partially deacylated derivatives were completely characterized by means of ESI FT-ICR mass spectrometry and chemical analysis. Preliminary immunological assays were performed, and a comparison with the lipid A structure of the phylogenetic proximal Halomonas magadiensis is also reported.

Gram‐Negative Extremophile Lipopolysaccharides: Promising Source of Inspiration for a New Generation of Endotoxin Antagonists

“…This was also observed in the case of the hexaacylated lipid A from the thermophilic bacterium T. hydrothermalis R‐type LPS, the very short acyl chains of which [namely,11:0(3‐OH) and 11:0] and their symmetric distribution on the glucosamine disaccharide backbone could be responsible for the observed weak immunopotency and the good antagonistic properties towards E. coli LPS toxicity . In contrast, lipid A species acting as agonists on the TLR4/MD‐2 complex, such as those from H. pantelleriensis and A. delamerensis , might also have great potential from a pharmaceutical point of view. As an example, the observation of the preferential induction of one defined type of immune response and not another, as in case of the H. pantelleriensis lipid A, could offer the possibility to use such extremophile lipid A as a starting point for ad hoc synthesized derivatives to employ as immunoadjuvants.…”

“…Very recently, Carillo et al have elucidated the H. pantelleriensis lipid A structure (Figure b), showing a family of species differing in the acylation profile with 12:0(3‐OH) units as primary fatty acids and 10:0 and 12:0 units as secondary fatty acids linked to the N ‐acyl residues at positions 2 and 2′ of the glucosamine backbone, respectively. Lipid A species lacking a phosphate group or the primary ester‐linked 12:0(3‐OH) on the reducing glucosamine moiety were also detected (Figure b) . Interestingly, Carillo et al have also observed the capability of H. pantelleriensis lipid A to induce a Th1‐type immune response by triggering the production of IFN‐γ and TNF‐α, whereas the Th2‐type cytokine release IL‐4 and regulatory IL‐10 were only slightly induced.…”

“…Interestingly, Carillo et al have also observed the capability of H. pantelleriensis lipid A to induce a Th1‐type immune response by triggering the production of IFN‐γ and TNF‐α, whereas the Th2‐type cytokine release IL‐4 and regulatory IL‐10 were only slightly induced. This discovery raised the possibility of using such lipid A, or ad hoc synthesized derivatives, as an immunoadjuvant …”

“…In contrast, lipid A species acting as agonists on the TLR4/MD‐2 complex, such as those from H. pantelleriensis and A. delamerensis , might also have great potential from a pharmaceutical point of view. As an example, the observation of the preferential induction of one defined type of immune response and not another, as in case of the H. pantelleriensis lipid A, could offer the possibility to use such extremophile lipid A as a starting point for ad hoc synthesized derivatives to employ as immunoadjuvants.…”