Abstract
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.
Highlights
Klebsiella pneumoniae is a common cause of nosocomial pneumonia, septicemia, and urinary tract infections; a recent US study found the bacterium to be the third most commonly
The lpxM gene was identified in the sequenced K. pneumoniae MGH75878 genome by homology to the lpxM genes from E. coli (AAC74925) and S. enterica var Typhimurium (AAL20805). 76% nucleotide homology exists between E. coli and K. pneumonaie lpxM genes with a probability score of 4.4eϪ119
The viability of K. pneumoniae lpxM mutants and their ability to express known virulence determinants at wild type levels allows a unique opportunity to study the role of lipid A in murine models of bacteremia and pneumonia
Summary
Klebsiella pneumoniae is a common cause of nosocomial pneumonia, septicemia, and urinary tract infections; a recent US study found the bacterium to be the third most commonly. MAY 25, 2007 VOLUME 282 NUMBER 21 isolated organism from intensive care wards and the most common species identified in blood cultures [1], with a similar trend reported among European hospitals [2]. This rising prevalence combined with the extensive spread of antibiotic-resistant strains, especially extended spectrum -lactamase (ESBL)-producing strains, will drive the search for alternative treatments and/or an effective vaccine against the bacterium. D, visualization of capsule by Maneval’s stain of B5055, B5055⌬lpxM, and B5055nm (non-mucoid mutant)
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