Presence of 2-hydroxymyristate on endotoxins is associated with death in neonates with Enterobacter cloacae complex septic shock

Luis A Augusto; Nadège Bourgeois-Nicolaos; Aude Breton; Simon Barreault; Enrique Hernandez Alonso; Stuti Gera; Véronique Faraut-Derouin; Nada Semaan; Daniele De Luca; Richard Chaby; Florence Doucet-Populaire; Pierre Tissières

doi:10.1016/j.isci.2021.102916

Presence of 2-hydroxymyristate on endotoxins is associated with death in neonates with Enterobacter cloacae complex septic shock

iScience. 2021 Jul 30;24(8):102916. doi: 10.1016/j.isci.2021.102916. eCollection 2021 Aug 20.

Authors

Luis A Augusto¹, Nadège Bourgeois-Nicolaos^{1

2}, Aude Breton¹, Simon Barreault^{1

3}, Enrique Hernandez Alonso¹, Stuti Gera², Véronique Faraut-Derouin², Nada Semaan^{1

3}, Daniele De Luca⁴, Richard Chaby¹, Florence Doucet-Populaire^{1

2}, Pierre Tissières^{1

3

5}

Affiliations

¹ Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198, Gif-sur-Yvette, France.
² Department of Bacteriology-Hygiene, AP-HP Paris-Saclay, Hôpital Antoine Béclère, Clamart Cedex, France.
³ Department of Pediatrics Intensive Care and Neonatal Medicine, AP-HP Université Paris -Saclay, Bicêtre Hospital, Paris, France.
⁴ Department of Neonatal Intensive Care, AP-HP Université Paris -Saclay, Hôpital Antoine Béclère, Clamart, France.
⁵ FHU Sepsis, AP-HP/Université Paris-Saclay/Inserm, Le Kremlin-Bicêtre, France.

Abstract

Enterobacter cloacae complex species are involved in infections among critically ill patients. After a recent E.cloacae outbreak of fulminant neonatal septic shock, we conducted a study to determine whether septic shock severity and its lethal consequence are related to structural features of the endotoxin (lipopolysaccharide [LPS]) of the strains isolated from hospitalized infants and more specifically its lipid A region. It appeared that the LPSs are very heterogeneous, carrying fifteen different molecular species of lipid A. The virulence was correlated with a structural feature identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry and gas chromatography coupled with mass spectrometry: the presence of 2-hydroxymyristic acid as a secondary substituent in lipid A. This is the first published evidence linking LPS structural moiety to neonatal sepsis outcome and opens the possibility of using this fatty acid marker as a detection tool for high-risk patients, which could help reduce their mortality.

Keywords: Immunology; Microbiology; Molecular Biology.