Genomic profiling reveals distinct routes to complement resistance in Klebsiella pneumoniae

Francesca L. Short, Gianna Di Sario, Nathalie T. Reichmann, Colin Kleanthous, Julian Parkhill, Peter W. Taylor

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

The serum complement system is a first line of defense against bacterial invaders. Resistance to killing by serum enhances the capacity of Klebsiella pneumoniae to cause infection, but it is an incompletely understood virulence trait. Identifying and characterizing the factors responsible for preventing activation of, and killing by, serum complement could inform new approaches to treatment of K. pneumoniae infections. Here, we used functional genomic profiling to define the genetic basis of complement resistance in four diverse serum-resistant K. pneumoniae strains (NTUH-K2044, B5055, ATCC 43816, and RH201207), and explored their recognition by key complement components. More than 90 genes contributed to resistance in one or more strains, but only three, rfaH, lpp, and arnD, were common to all four strains. Deletion of the antiterminator rfaH, which controls the expression of capsule and O side chains, resulted in dramatic complement resistance reductions in all strains. The murein lipoprotein gene lpp promoted capsule retention through a mechanism dependent on its C-terminal lysine residue; its deletion led to modest reductions in complement resistance. Binding experiments with the complement components C3b and C5b-9 showed that the underlying mechanism of evasion varied in the four strains: B5055 and NTUH-K2044 appeared to bypass recognition by complement entirely, while ATCC 43816 and RH201207 were able to resist killing despite being associated with substantial levels of C5b-9. All rfaH and lpp mutants bound C3b and C5b-9 in large quantities. Our findings show that, even among this small selection of isolates, K. pneumoniae adopts differing mechanisms and utilizes distinct gene sets to avoid complement attack.

Original languageEnglish
Article numbere00043-20
Number of pages19
JournalInfection and Immunity
Volume88
Issue number8
DOIs
Publication statusPublished - Aug 2020
Externally publishedYes

Keywords

  • Capsule
  • Complement resistance
  • Functional genomics
  • Klebsiella
  • Serum resistance
  • Tn-Seq
  • TraDIS
  • Transposon insertion sequencing

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