Phagosomal granulocytic ROS in septic patients induce the bacterial SOS response

Stecy Chollet; Ana Catalina Hernandez Padilla; Thomas Daix; Margaux Gaschet; Bruno François; Christophe Piguet; Nathalie Gachard; Sandra Da Re; Robin Jeannet; Marie-Cécile Ploy

doi:10.1016/j.isci.2024.109825

Phagosomal granulocytic ROS in septic patients induce the bacterial SOS response

iScience. 2024 Apr 26;27(6):109825. doi: 10.1016/j.isci.2024.109825. eCollection 2024 Jun 21.

Authors

Stecy Chollet¹, Ana Catalina Hernandez Padilla¹, Thomas Daix^{1

2

3}, Margaux Gaschet¹, Bruno François^{1

2

3}, Christophe Piguet⁴, Nathalie Gachard^{5

6}, Sandra Da Re¹, Robin Jeannet^{3

6}, Marie-Cécile Ploy¹

Affiliations

¹ University Limoges, Inserm, CHU Limoges, RESINFIT, U 1092, F-87000 Limoges, France.
² CHU Limoges, Service de Réanimation Polyvalente, Limoges, France.
³ Inserm CIC 1435, Limoges, France.
⁴ CHU Limoges, Département de pédiatrie médicale, Limoges, France.
⁵ CHU Limoges, Laboratoire d'hématologie, Limoges, France.
⁶ CNRS UMR 7276, Inserm UMR 1262, Université de Limoges, Limoges, France.

Abstract

Septic patients with worst clinical prognosis have increased circulating immature granulocytes (IG), displaying limited phagocytosis and reactive oxygen species (ROS) production. Here, we developed an ex vivo model of incubation of human granulocytes, from septic patients or healthy donors, with Escherichia coli. We showed that the ROS production in Sepsis-IG is lower due to decreased activation and protein expression of the NADPH oxidase complex. We also demonstrated that the low level of ROS production and lower phagocytosis of IG in sepsis induce the bacterial SOS response, leading to the expression of the SOS-regulated quinolone resistance gene qnrB2. Without antimicrobial pressure, the sepsis immune response alone may promote antibiotic resistance expression.

Keywords: Bacteriology; Immunology; Microbiology.