Assessment of hypermucoviscosity as a virulence factor for experimental Klebsiella pneumoniae infections: comparative virulence analysis with hypermucoviscosity-negative strain - PubMed (original) (raw)

Comparative Study

Assessment of hypermucoviscosity as a virulence factor for experimental Klebsiella pneumoniae infections: comparative virulence analysis with hypermucoviscosity-negative strain

Yi-Chun Lin et al. BMC Microbiol. 2011.

Abstract

Background: Klebsiella pneumoniae displaying the hypermucoviscosity (HV) phenotype are considered more virulent than HV-negative strains. Nevertheless, the emergence of tissue-abscesses-associated HV-negative isolates motivated us to re-evaluate the role of HV-phenotype.

Results: Instead of genetically manipulating the HV-phenotype of K. pneumoniae, we selected two clinically isolated K1 strains, 1112 (HV-positive) and 1084 (HV-negative), to avoid possible interference from defects in the capsule. These well-encapsulated strains with similar genetic backgrounds were used for comparative analysis of bacterial virulence in a pneumoniae or a liver abscess model generated in either naïve or diabetic mice. In the pneumonia model, the HV-positive strain 1112 proliferated to higher loads in the lungs and blood of naïve mice, but was less prone to disseminate into the blood of diabetic mice compared to the HV-negative strain 1084. In the liver abscess model, 1084 was as potent as 1112 in inducing liver abscesses in both the naïve and diabetic mice. The 1084-infected diabetic mice were more inclined to develop bacteremia and had a higher mortality rate than those infected by 1112. A mini-Tn5 mutant of 1112, isolated due to its loss of HV-phenotype, was avirulent to mice.

Conclusion: These results indicate that the HV-phenotype is required for the virulence of the clinically isolated HV-positive strain 1112. The superior ability of the HV-negative stain 1084 over 1112 to cause bacteremia in diabetic mice suggests that factors other than the HV phenotype were required for the systemic dissemination of K. pneumoniae in an immunocompromised setting.

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Figures

Figure 1

Figure 1

Prevalence of HV phenotype among clinical K. pneumoniae isolates. (A) A mucoviscous string formed between an inoculation loop and the colony of a HV-positive strain. (B) Occurrence of HV-positive (black columns) or HV-negative (white columns) isolates in patients with or without diabetic mellitus (DM or Non-DM). (C) Prevalence of HV-positive K. pneumoniae among patients suffering from various infections, including KLA, non-hepatic abscess, pneumonia, primary bacteremia, and secondary bacteremia. (D) Dendrogram of the HV-positive strain 1112 and-negative strain 1084. Genetic similarities were calculated using UPGMA.

Figure 2

Figure 2

Analysis of comparative virulence analysis for HV-positive and -negative K. pneumoniae. In the pneumonia model, bacterial counts in the lung (A) and blood (B) at 20 hours post-infection with the HV-negative 1084 or the HV-positive 1112 were determined in diabetic mice (filled columns) or naïve mice (striped columns). In the KLA model, 1084 (C, E) and 1112 (D, F) were orally inoculated into diabetic mice with inoculums of 105 CFU (C, D) or into naïve mice with inoculums of 108 CFU (E, F). Twenty microliters of blood was removed from the retroorbital sinus of mice at 24 h, 48 h, and 72 h post-inoculation; and the bacterial loads were determined using the plate-counting method. Each symbol represents the data obtained from a particular mouse. The bacterial load recovered from a particular mouse tissue, which was beyond the detection limit (approximately 40 CFU), is not represented. Survival of these mice was monitored daily for seven days. The survival rate of the 1112-infected (solid line) or the 1084-infected (dotted line) diabetic (G) or naïve (H) mice was determined by Kaplan-Meier analysis. Data were compiled from results obtained from three independent experiments.

Figure 3

Figure 3

Histopathological examination of livers. Mice that had been orally inoculated with PBS (A, B), HV-negative strain 1084 (C, D), or HV-positive strain 1112 (E, F) (in diabetic mice) (A, C, E) with inoculums of 105 CFU or in naive mice with inoculums of 108 CFU (B, D, F) were euthanized at seven days post-inoculation. Arrows indicate the area of PMN infiltration and aggregation (100 × magnification). Scale bar represents a distance of 1 μm.

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