Genomic Profiling Reveals Distinct Routes To Complement Resistance in Klebsiella pneumoniae

The serum complement system is a first line of defense against bacterial invaders. Resistance to killing by serum enhances the capacity of to cause infection, but it is an incompletely understood virulence trait. Identifying and characterizing the factors responsible for preventing activation of, an...

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Bibliographic Details
Published in:Infection and immunity 2020-07, Vol.88 (8)
Main Authors: Short, Francesca L, Di Sario, Gianna, Reichmann, Nathalie T, Kleanthous, Colin, Parkhill, Julian, Taylor, Peter W
Format: Article
Language:English
Subjects:
Bacterial Outer Membrane Proteins - genetics
Bacterial Outer Membrane Proteins - immunology
Blood Bactericidal Activity - immunology
Carboxy-Lyases - deficiency
Carboxy-Lyases - genetics
Carboxy-Lyases - immunology
Complement C3b - genetics
Complement C3b - immunology
Complement Membrane Attack Complex - genetics
Complement Membrane Attack Complex - immunology
DNA Transposable Elements
Gene Expression Profiling
Gene Expression Regulation, Bacterial - immunology
Gene Library
Genes, Bacterial
Humans
Immune Evasion
Klebsiella Infections - immunology
Klebsiella Infections - microbiology
Klebsiella pneumoniae - genetics
Klebsiella pneumoniae - immunology
Klebsiella pneumoniae - pathogenicity
Molecular Pathogenesis
Mutation
Peptide Elongation Factors - deficiency
Peptide Elongation Factors - genetics
Peptide Elongation Factors - immunology
Sequence Analysis, DNA
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Summary:The serum complement system is a first line of defense against bacterial invaders. Resistance to killing by serum enhances the capacity of 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 infections. Here, we used functional genomic profiling to define the genetic basis of complement resistance in four diverse serum-resistant 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, , , and , were common to all four strains. Deletion of the antiterminator , which controls the expression of capsule and O side chains, resulted in dramatic complement resistance reductions in all strains. The murein lipoprotein gene 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 and mutants bound C3b and C5b-9 in large quantities. Our findings show that, even among this small selection of isolates, adopts differing mechanisms and utilizes distinct gene sets to avoid complement attack.
ISSN:0019-9567
1098-5522
DOI:10.1128/IAI.00043-20