Secondary acylation of Klebsiella pneumoniae lipopolysaccharide contributes to sensitivity to antibacterial peptides.
Klebsiella pneumoniae is an important cause of nosocomial Gram-negative sepsis. Lipopolysaccharide (LPS) is considered to be a major virulence determinant of this encapsulated bacterium and most mutations to the lipid A anchor of LPS are conditionally lethal to the bacterium. We studied the role of LPS acylation in K. pneumoniae disease pathogenesis by using a mutation of lpxM (msbB/waaN), which encodes the enzyme responsible for late secondary acylation of immature lipid A molecules. A K. pneumoniae B5055 (K2:O1) lpxM mutant was found to be attenuated for growth in the lungs in a mouse pneumonia model leading to reduced lethality of the bacterium. B5055DeltalpxM exhibited similar sensitivity to phagocytosis or complement-mediated lysis than B5055, unlike the non-encapsulated mutant B5055nm. In vitro, B5055DeltalpxM showed increased permeability of the outer membrane and an increased susceptibility to certain antibacterial peptides suggesting that in vivo attenuation may be due in part to sensitivity to antibacterial peptides present in the lungs of BALB/c mice. These data support the view that lipopolysaccharide acylation plays a important role in providing Gram-negative bacteria some resistance to structural and innate defenses and especially the antibacterial properties of detergents (e.g. bile) and cationic defensins.
Clements
Abigail
A
CRC for Vaccine Technology in the Department of Microbiology & Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.
Tull
Dedreia
D
Jenney
Adam W
AW
Farn
Jacinta L
JL
Kim
Sang-Hyun
SH
Bishop
Russell E
RE
McPhee
Joseph B
JB
Hancock
Robert E W
RE
Hartland
Elizabeth L
EL
Pearse
Martin J
MJ
Wijburg
Odilia L C
OL
Jackson
David C
DC
McConville
Malcolm J
MJ
Strugnell
Richard A
RA
D000215:Acylation; D000818:Animals; D000900:Anti-Bacterial Agents / Q000276:immunology*; D016667:Bacterial Capsules / Q000235:genetics / Q000276:immunology; D001770:Blood Bactericidal Activity / Q000235:genetics / Q000276:immunology; D023082:Defensins / Q000276:immunology*; D004195:Disease Models, Animal; D004352:Drug Resistance, Microbial; D006801:Humans; D007710:Klebsiella Infections / Q000235:genetics / Q000276:immunology*; D007711:Klebsiella pneumoniae / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D008050:Lipid A / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000235:genetics / Q000276:immunology*; D018805:Sepsis / Q000235:genetics / Q000276:immunology
D000900:Anti-Bacterial Agents; D023082:Defensins; D008050:Lipid A