The Impact of Colistin Resistance on the Activation of Innate Immunity by Lipopolysaccharide Modification.
José Avendaño-OrtizManuel Ponce-AlonsoEmilio Llanos-GonzálezHugo Barragán-PradaRaquel Barbero-HerranzRoberto Lozano-RodríguezFrancesc J Márquez-GarridoJosé María Hernández-PérezMaría-Isabel MorosiniRafael CantónRosa Del CampoEduardo López-CollazoPublished in: Infection and immunity (2023)
Colistin resistance is acquired by different lipopolysaccharide (LPS) modifications. We proposed to evaluate the of effect in vivo colistin resistance acquisition on the innate immune response. We used a pair of ST11 clone Klebsiella pneumoniae strains: an OXA-48, CTX-M-15 K. pneumoniae strain susceptible to colistin (CS-Kp) isolated from a urinary infection and its colistin-resistant variant (CR-Kp) from the same patient after prolonged treatment with colistin. No mutation of previously described genes for colistin resistance ( pmrA , pmrB , mgrB , phoP/Q, arnA, arnC, arnT, ugdH , and crrAB ) was found in the CR-Kp genome; however, LPS modifications were characterized by negative-ion matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. The strains were cocultured with human monocytes to determine their survival after phagocytosis and induction to apoptosis. Also, monocytes were stimulated with bacterial LPS to study cytokine and immune checkpoint production. The addition of 4-amino-4-deoxy-l-arabinose (Ara4N) to lipid A of CR-Kp accounted for the colistin resistance. CR-Kp survived significantly longer inside human monocytes after being phagocytosed than did the CS-Kp strain. In addition, LPS from CR-Kp induced both higher apoptosis in monocytes and higher levels of cytokine and immune checkpoint production than LPS from CS-Kp. Our data reveal a variable impact of colistin resistance on the innate immune system, depending on the responsible mechanism. Adding Ara4N to LPS in K. pneumoniae increases bacterial survival after phagocytosis and elicits a higher inflammatory response than its colistin-susceptible counterpart.
Keyphrases
- klebsiella pneumoniae
- inflammatory response
- escherichia coli
- acinetobacter baumannii
- multidrug resistant
- pseudomonas aeruginosa
- mass spectrometry
- gram negative
- drug resistant
- lps induced
- toll like receptor
- lipopolysaccharide induced
- anti inflammatory
- endothelial cells
- genome wide
- dendritic cells
- cell death
- electronic health record
- cell proliferation
- gene expression
- endoplasmic reticulum stress
- machine learning
- ms ms
- dna methylation
- liquid chromatography
- signaling pathway
- transcription factor
- stress induced
- simultaneous determination