KPC-producing, multidrug-resistant Klebsiella pneumoniae sequence type 258 as a typical opportunistic pathogen

Abstract

The virulence of a KPC-producing Klebsiella pneumoniae sequence type 258 (ST258) strain representing those circulating in Greece was assessed in a mouse septicemia model. The strain was virtually avirulent (50% lethal dose, >10(8) and 5 × 10(7) CFU for immunocompetent and neutropenic animals, respectively). Also, it was highly susceptible to serum killing, rapidly phagocytosed in vitro, and classified as K41, which is not among the virulent capsular types. The findings indirectly support the notion that high ST258-associated mortality is largely due to inefficient antimicrobial treatment.

Fig 1

Kaplan-Meier survival curves of immunocompetent (i and ii) and neutropenic (iii and iv) mice infected with K. pneumoniae ST258 strain L-78 (i and iii) or comparator strain ATCC 43816 (ii and iv). Note that the range of inocula of the latter strain was smaller.

Fig 2

(A) Bactericidal activity of human serum against ST258 and ATCC 43816. (B) Representative fluorescence-activated cell sorting histogram plots from three independent experiments (top) and rates of phagocytosis of ST258 and ATCC 43816 by J774A.1 murine macrophages (bottom). Macrophages were exposed to CFDA-SE-labeled bacterial cells (multiplicity of infection = 25) for 15, 30, 60, or 120 min at 37°C and analyzed by flow cytometry. For each sample, 10,000 cells were analyzed. The gray histograms at the top represent cells in the absence of bacteria (negative control), and the black histograms represent cells in the presence of bacteria. The results at the bottom are expressed as the percentages of macrophages that internalized ST258 or ATCC 43816 (percent phagocytosis) versus time. The results shown are the means of three independent experiments ± the standard deviations.