Complement Susceptibility in Relation to Genome Sequence of Recent Klebsiella pneumoniae Isolates from Thai Hospitals

Author:

Loraine Jessica1,Heinz Eva2,De Sousa Almeida Jessica1,Milevskyy Oleksandr1,Voravuthikunchai Supayang P.3,Srimanote Potjanee4,Kiratisin Pattarachai5,Thomson Nicholas R.26,Taylor Peter W.1

Affiliation:

1. School of Pharmacy, University College London, London, United Kingdom

2. Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom

3. Faculty of Science, Prince of Songkla University, Songkla, Thailand

4. Faculty of Allied Health Sciences, Thammasat University, Pathumtanee, Thailand

5. Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

6. London School of Hygiene and Tropical Medicine, London, United Kingdom

Abstract

Multidrug-resistant Klebsiella pneumoniae is responsible for an increasing proportion of nosocomial infections, and emerging hypervirulent K. pneumoniae clones now cause severe community-acquired infections in otherwise healthy individuals. These bacteria are adept at circumventing immune defenses, and most survive and grow in serum; their capacity to avoid C′-mediated destruction is correlated with their invasive potential. Killing of Gram-negative bacteria occurs following activation of the C′ cascades and stable deposition of C5b-9 MACs onto the OM. For Klebsiella , studies with mutants and conjugants have invoked capsules, lipopolysaccharide O-side chains, and OM proteins as determinants of C′ resistance, although the precise roles of the macromolecules are unclear. In this study, we sequenced 164 Klebsiella isolates with different C′ susceptibilities to identify genes involved in resistance. We conclude that no single OM constituent can account for resistance, which is likely to depend on biophysical properties of the target bilayer.

Funder

RCUK | Medical Research Council

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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