Abstract
Klebsiella pneumoniae is the common cause of a global emerging infectious disease, community-acquired pyogenic liver abscess (PLA). Capsular polysaccharide (CPS) and lipopolysaccharide (LPS) are critical for this microorganism's ability to spread through the blood and to cause sepsis. While CPS type K1 is an important virulence factor in K. pneumoniae causing PLA, the role of LPS in PLA is not clear. Here, we characterize the role of LPS O antigen in the pathogenesis of K. pneumoniae causing PLA. NTUH-K2044 is a LPS O1 clinical strain; the presence of the O antigen was shown via the presence of 1,3-galactan in the LPS, and of sequences that align with the wb gene cluster, known to produce O-antigen. Serologic analysis of K. pneumoniae clinical isolates demonstrated that the O1 serotype was more prevalent in PLA strains than that in non-tissue-invasive strains (38/42 vs. 9/32, P<0.0001). O1 serotype isolates had a higher frequency of serum resistance, and mutation of the O1 antigen changed serum resistance in K. pneumoniae. A PLA-causing strain of CPS capsular type K2 and LPS serotype O1 (i.e., O1:K2 PLA strain) deleted for the O1 synthesizing genes was profoundly attenuated in virulence, as demonstrated in separate mouse models of septicemia and liver abscess. Immunization of mice with the K2044 magA-mutant (K1 − O1) against LPS O1 provided protection against infection with an O1:K2 PLA strain, but not against infection with an O1:K1 PLA strain. Our findings indicate that the O1 antigen of PLA-associated K. pneumoniae contributes to virulence by conveying resistance to serum killing, promoting bacterial dissemination to and colonization of internal organs after the onset of bacteremia, and could be a useful vaccine candidate against infection by an O1:K2 PLA strain.
Highlights
Community-acquired pyogenic liver abscess (PLA) is an emerging infectious disease
According to recent epidemiologic studies, 80% of cases of PLA were caused by Klebsiella pneumoniae; 60% to 80% of the K. pneumoniae isolates causing these cases belonged to the K1 capsular type, and 10% to 14% isolates belonged to the K2 capsular type in Asia [1,2]
We examined the distribution of O1 serotypes in PLA and non–tissue-invasive K. pneumoniae clinical isolates; determined whether a correlation exists between O1 serotype and resistance to killing by serum; explored the role of the O1 antigen of K. pneumoniae in the pathogenesis of PLA; and investigated whether antiserum raised against LPS O1 could protect against PLA-associated K. pneumoniae infection
Summary
Community-acquired pyogenic liver abscess (PLA) is an emerging infectious disease. According to recent epidemiologic studies, 80% of cases of PLA were caused by Klebsiella pneumoniae; 60% to 80% of the K. pneumoniae isolates causing these cases belonged to the K1 capsular type, and 10% to 14% isolates belonged to the K2 capsular type in Asia [1,2]. Capsular polysaccharide (CPS) has been shown to be essential for the virulence of this pathogen [3]. As the outermost components of the bacterial surface, CPS and the O-antigen portion of the lipopolysaccharide (LPS) are among the first bacteria-derived molecules to be encountered by the host’s innate immune system. Both CPS and LPS components are important pathogenic determinants in K. pneumonia-caused pneumonia and bacteremia [5,6,7], but little is known about the virulence role of LPS in K. pneumoniae PLA
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