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 M. Hocking, Leila Jebeli, Hanwei Cao, Abigail Clements, Adam Jenney, Trevor Lithgow, Richard A. Strugnell
Abstract
Bacterial capsules, typically comprised of complex sugars, enable pathogens to avoid key host responses to infection, including phagocytosis. These capsules are synthesized within the bacteria, exported through the outer envelope, and then secured to the external surface of the organism by a force or forces that are incompletely described. This study shows that in the important hospital pathogen Klebsiella pneumoniae, the polysaccharide capsule is retained by interactions with other surface sugars, especially the repeated sugar molecule of the LPS molecule in Gram-negative bacteria known as "O antigen." This O antigen is joined to the LPS molecule by ligation, and loss of the enzyme responsible for ligation, a protein called WaaL, results in reduced encapsulation. Since capsules are essential to the virulence of many pathogens, WaaL might provide a target for new antimicrobial development, critical to the control of pathogens like K. pneumoniae that have become highly drug resistant.