Genomic Profiling Reveals Distinct Routes To Complement Resistance in Klebsiella pneumoniae.

Infection and Immunity
Francesca L ShortPeter W Taylor

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 t...Continue Reading

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Citations

Jan 26, 2021·Frontiers in Microbiology·Bing Wang, Irina Artsimovitch
Mar 4, 2021·Proceedings. Biological Sciences·Amandine BuffetOlaya Rendueles
Feb 10, 2021·Infection and Immunity·Shekina Gonzalez-FerrerDaria Van Tyne
Mar 12, 2021·Clinical Microbiology Reviews·Caitlyn L HolmesMichael A Bachman
Jan 30, 2021·Pathogens and Disease·Sebastian BruchmannFrancesca L Short
Jul 6, 2021·Frontiers in Cellular and Infection Microbiology·George Blundell-HunterPeter W Taylor

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Datasets Mentioned

BETA
PRJEB20200

Methods Mentioned

BETA
uronic
Fluorescence microscopy
density gradient centrifugation
PCR

Software Mentioned

BioTraDIS
FIJI
GraphPad
FlowJo
bacteria
EdgeR
BLASTp search
R script
BioCyc
Kaptive

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