Complement killing of clinical Klebsiella pneumoniae isolates is serum concentration dependent

Katharina V Opstrup, Tue B Bennike, Gunna Christiansen, Svend Birkelund*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

2 Citations (Scopus)

Abstract

Klebsiella pneumoniae is an opportunistic gram-negative pathogen causing serious infections, including sepsis. In plasma, activation of the complement cascades is important for killing bacteria. Thirty clinical Klebsiella spp. blood isolates were analyzed for serum susceptibility in 75% normal human serum (NHS). Twenty-two were serum resistant and eight were serum sensitive, and subsequently tested in 5-75% NHS. Two isolates were killed in 5% and the remaining six in 50%-75% NHS. The two 5% sensitive isolates showed binding of complement (C)4 and C3 in 5% NHS with formation of membrane attack complex (MAC). Inhibition of the classical/lectin mediated pathways (CP/LP) using a C4 specific nanobody, hC4Nb8, led to survival of both isolates in 5% NHS. Using nanobody hC3Nb1, inhibiting the alternative pathway (AP), the isolates were killed in 5% NHS, and amplification of the CP/LP by AP was not necessary for killing. Sole AP killing of these isolates when inhibiting CP/LP with hC4Nb8 was observed in 50% NHS, stressing the concentration dependent functionality of AP. For the less sensitive isolates, killing required activation of CP/LP and AP demonstrated by inhibition with nanobodies. AP inhibition resulted in no C3 deposition on the serum resistant isolate, supporting that AP was the sole activation pathway.

Original languageEnglish
Article number105074
JournalMicrobes and Infection
Volume25
Issue number4
ISSN1286-4579
DOIs
Publication statusPublished - May 2023

Bibliographical note

Copyright © 2022. Published by Elsevier Masson SAS.

Keywords

  • Alternative pathway
  • Bacterial capsules
  • Complement system
  • Klebsiella pneumoniae
  • Membrane attack complex
  • Serum resistance
  • Complement System Proteins
  • Complement Membrane Attack Complex
  • Complement Activation
  • Humans
  • Serum
  • Complement Pathway, Alternative

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