O antigen seroepidemiology of Klebsiella clinical isolates and implications for immunoprophylaxis of Klebsiella infections

Trautmann, Matthias; Held, T.; Cross, Alan S.

doi:10.1016/j.vaccine.2003.11.026

Cited by 41 publications

(56 citation statements)

References 35 publications

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“…d Nucleotide sequencing was unsuccessful (i.e., all of the PCR primer pairs designed from the wb sequence of the O3 reference strain yielded negative results) (see Table S4 in the supplemental material), which indicates that this strain was incorrectly assigned to the O3 serotype. (21). Both studies show that O7, the type not included in our current O-genotyping scheme, is extremely rare among K. pneumoniae clinical isolates.…”

Section: Discussionmentioning

confidence: 88%

“…Traditional O serotyping such as tube agglutination is interfered with by the masking effect of heat-stable CPS (18), which necessitates the use of capsule-free mutants (19). The introduction of an inhibition enzyme-linked immunosorbent assay (iELISA) has obviated the need for mutants (18,20,21). Nevertheless, the procedure is still cumbersome and the reagents are not commercially available.…”

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confidence: 99%

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confidence: 99%

“…Nevertheless, the procedure is still cumbersome and the reagents are not commercially available. Furthermore, serological cross-reactivity exists between biochemically distinctive O types due to similarities in their O-antigen structures (19,21,22). For example, serological cross-reactions occur between O1, O2(2a), and O2(2a,2c) because the O-antigen polysaccharides in O1 (D-galactan I and D-galactan II), O2(2a) (D-galactan I alone), and O2(2a,2c) (D-galactan I and 2c polysaccharide) have a common element: D-galactan I (23,24).…”

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confidence: 99%

“…This study aimed to sequence and analyze the genetic determinants of the nine O serotypes (O1, O2a, O2ac, O3, O4, O5, O8, O9, and O12) that have been found in clinical K. pneumoniae isolates (13,18,20,21,31) and to create and validate a novel genotyping scheme for determining the O-antigen types in K. pneumoniae.…”

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confidence: 99%

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Rapid and Accurate Determination of Lipopolysaccharide O-Antigen Types in Klebsiella pneumoniae with a Novel PCR-Based O-Genotyping Method

et al. 2016

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b Klebsiella pneumoniae, a Gram-negative bacillus that causes life-threatening infections in both hospitalized patients and ambulatory persons, can be classified into nine lipopolysaccharide (LPS) O-antigen serotypes. The O-antigen type has important clinical and epidemiological significance. However, K. pneumoniae O serotyping is cumbersome, and the reagents are not commercially available. To overcome the limitations of conventional serotyping methods, we aimed to create a rapid and accurate PCR method for K. pneumoniae O genotyping. We sequenced the genetic determinants of LPS O antigen from serotypes O1, O2a, O2ac, O3, O4, O5, O8, O9, and O12. We established a two-step genotyping scheme, based on the two genomic regions associated with O-antigen biosynthesis. The first set of PCR primers, which detects alleles at the wzm-wzt loci of the wb gene cluster, distinguishes between O1/O2, O3, O4, O5, O8, O9, and O12. The second set of PCR primers, which detects alleles at the wbbY region, further differentiates between O1, O2a, and O2ac. We verified the specificity of O genotyping against the O-serotype reference strains. We then tested the sensitivity and specificity of O genotyping in K. pneumoniae, using the 56 K-serotype reference strains with known O serotypes determined by an inhibition enzyme-linked immunosorbent assay (iELISA). There is a very good correlation between the O genotypes and classical O serotypes. Three discrepancies were observed and resolved by nucleotide sequencing-all in favor of O genotyping. The PCR-based O genotyping, which can be easily performed in clinical and research microbiology laboratories, is a rapid and accurate method for determining the LPS O-antigen types of K. pneumoniae isolates. Klebsiella pneumoniae is an encapsulated Gram-negative bacillus that frequently causes outbreaks of nosocomial infections in hospitalized patients (1-3). It can also affect ambulatory persons and cause community-acquired invasive diseases, including pyogenic liver abscess, endophthalmitis, meningitis, empyema, lung abscess, and necrotizing fasciitis (4-9). The worldwide emergence of multidrug-resistant strains and hypervirulent strains of K. pneumoniae has become an increasing clinical challenge and public health concern (10, 11).K. pneumoniae strains can be distinguished by their capsular polysaccharide (CPS) K-antigen types (77 serotypes) and lipopolysaccharide (LPS) O-antigen types (9 serotypes) (2). The K type and O type of K. pneumoniae both have important clinical and epidemiological significance (8, 12, 13). K1 clonal complex 23 is a newly emerged hypervirulent clade, which causes pyogenic liver abscesses with septic ocular or central nervous system complications (8,14,15). Likewise, O1 is associated with hypervirulent strains that cause pyogenic liver abscess (12). The O:K typing also helps establish the clonality of K. pneumoniae in nosocomial outbreak investigations (13). K-genotyping methods are now available for quickly and correctly determining the K types in K. pneumoniae (8,16,17). O...

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Section: Discussionmentioning

confidence: 88%

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confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

mentioning

confidence: 99%

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Rapid and Accurate Determination of Lipopolysaccharide O-Antigen Types in Klebsiella pneumoniae with a Novel PCR-Based O-Genotyping Method

et al. 2016

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Production of a Promising Biosynthetic Self‐Assembled Nanoconjugate Vaccine against Klebsiella Pneumoniae Serotype O2 in a General Escherichia Coli Host

Peng¹,

Wu²,

Wang³

et al. 2021

Advanced Science

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Klebsiella pneumoniae has emerged as a severe opportunistic pathogen with multiple drug resistances. Finding effective vaccines against this pathogen is urgent. Although O-polysaccharides (OPS) of K. pneumoniae are suitable antigens for the preparation of vaccines given their low levels of diversity, the low immunogenicity (especially serotype O2) limit their application. In this study, a general Escherichia coli host system is developed to produce a nanoscale conjugate vaccine against K. pneumoniae using the Nano-B5 self-assembly platform. The experimental data illustrate that this nanoconjugate vaccine can induce an efficient humoral immune response in draining lymph nodes (dLNs) and elicit high titers of the IgG antibody against bacterial lipopolysaccharide (LPS). The ideal prophylactic effects of these nanoconjugate vaccines are further demonstrated in mouse models of both systemic and pulmonary infection. These results demonstrate that OPS with low immunogenicity can be changed into an effective antigen, indicating that other haptens may be applicable to this strategy in the future. To the knowledge, this is the first study to produce biosynthetic nanoconjugate vaccines against K. pneumoniae in E. coli, and this strategy can be applied to the development of other vaccines against pathogenic bacteria.

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Development of an Anti-Endotoxin Vaccine for Sepsis

Cross

2010

Subcellular Biochemistry

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Gram-negative bacterial lipopolysaccharide (LPS, endotoxin) is an important initiator of sepsis, a clinical syndrome that is a leading cause of death in intensive care units. Vaccines directed against core LPS structures that are widely conserved among Gram-negative bacteria (GNB) have been developed for the treatment and/or prevention of sepsis. Killed whole bacterial vaccines (E. coli O111:B4, J5 [Rc chemotype] mutant and S. minnesota, Re chemotype) protected mice against experimental sepsis. Human J5 immune antisera reduced the mortality from GNB sepsis in a large controlled clinical trial; however, subsequent clinical studies with antiendotoxin antibodies did not demonstrate protective efficacy in sepsis. Multiple clinical studies have since demonstrated a correlation between the level of circulating antibodies to LPS core and morbidity and mortality in different clinical settings. We therefore developed a subunit vaccine by combining detoxified J5 LPS (J5 dLPS) with the outer membrane protein (OMP) from group B N. meningitidis. This vaccine was highly efficacious in experimental models of sepsis and progressed to phase 1 clinical trial. While well-tolerated, this vaccine induced only 3-4-fold increases in anti-J5 dLPS antibody. Addition of the TLR9 agonist, oligodeoxynucleotide with a CpG motif, as adjuvant to the vaccine increased antibody levels in mice and the vaccine/CpG combination will progress to phase 1 human study. Additional vaccines in which the core glycolipid was either conjugated to carrier protein or incorporated into liposomes have been developed, but have not progressed to clinical trial. Should an antiendotoxin vaccine become available, a new immunization strategy directed towards distinct populations at risk will be required.

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O antigen seroepidemiology of Klebsiella clinical isolates and implications for immunoprophylaxis of Klebsiella infections

Cited by 41 publications

References 35 publications

Rapid and Accurate Determination of Lipopolysaccharide O-Antigen Types in Klebsiella pneumoniae with a Novel PCR-Based O-Genotyping Method

Rapid and Accurate Determination of Lipopolysaccharide O-Antigen Types in Klebsiella pneumoniae with a Novel PCR-Based O-Genotyping Method

Production of a Promising Biosynthetic Self‐Assembled Nanoconjugate Vaccine against Klebsiella Pneumoniae Serotype O2 in a General Escherichia Coli Host

Development of an Anti-Endotoxin Vaccine for Sepsis

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