LPS O Antigen Plays a Key Role in Klebsiella pneumoniae Capsule Retention

Shweta Singh, Jonathan J. Wilksch, Rhys A. Dunstan, Anna Mularski, Nancy Wang, Dianna Hocking, Leila Jebeli, Hanwei Cao, Abigail Clements, Adam W.J. Jenney, Trevor Lithgow, Richard A. Strugnell

Research output: Contribution to journalArticleResearchpeer-review

9 Citations (Scopus)

Abstract

Despite the importance of encapsulation in bacterial pathogenesis, the biochemical mechanisms and forces that underpin retention of capsule by encapsulated bacteria are poorly understood. In Gram-negative bacteria, there may be interactions between lipopolysaccharide (LPS) core and capsule polymers, between capsule polymers with retained acyl carriers and the outer membrane, and in some bacteria, between the capsule polymers and Wzi, an outer membrane protein lectin. Our transposon studies in Klebsiella pneumoniae B5055 identified additional genes that, when insertionally inactivated, resulted in reduced encapsulation. Inactivation of the gene waaL, which encodes the ligase responsible for attaching the repeated O antigen of LPS to the LPS core, resulted in a significant reduction in capsule retention, measured by atomic force microscopy. This reduction in encapsulation was associated with increased sensitivity to human serum and decreased virulence in a murine model of respiratory infection and, paradoxically, with increased biofilm formation. The capsule in the WaaL mutant was physically smaller than that of the Wzi mutant of K. pneumoniae B5055. These results suggest that interactions between surface carbohydrate polymers may enhance encapsulation, a key phenotype in bacterial virulence, and provide another target for the development of antimicrobials that may avoid resistance issues associated with growth inhibition.

Original languageEnglish
Number of pages18
JournalMicrobiology Spectrum
Volume10
Issue number4
DOIs
Publication statusPublished - Aug 2022

Keywords

  • capsule
  • encapsulation
  • Klebsiella
  • LPS
  • O antigen
  • retention
  • virulence

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