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.

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

“…Likewise, the virulence of KPC-carrying ST258 strains is being tested in a variety of assays and infection models to determine whether wide dissemination correlates with increased virulence. Notably, strains of ST258 are less virulent in mice than another K. pneumoniae strain, ATCC 43816 (ST439), which is frequently used in mouse studies (21,22). Furthermore, in mouse infections, an ST258 strain was markedly more sensitive to clearance by monocytes than by neutrophils (22), and in cell culture, an ST258 strain was phagocytosed by murine macrophages more efficiently than an ST439 strain (ATCC 43813) (21).…”

“…Notably, strains of ST258 are less virulent in mice than another K. pneumoniae strain, ATCC 43816 (ST439), which is frequently used in mouse studies (21,22). Furthermore, in mouse infections, an ST258 strain was markedly more sensitive to clearance by monocytes than by neutrophils (22), and in cell culture, an ST258 strain was phagocytosed by murine macrophages more efficiently than an ST439 strain (ATCC 43813) (21). The inability of mouse neutrophils to effectively target strains of ST258 is consistent with data from recent studies with human neutrophils, where an ST258 strain was more resistant to killing by human neutrophils than a closely related ST11 strain or a Staphylococcus aureus control (23,24).…”

The Role of Epidemic Resistance Plasmids and International High-Risk Clones in the Spread of Multidrug-Resistant Enterobacteriaceae

“…ST258 lacks well-characterized K. pneumoniae virulence factors, including the K1, K2, and K5 capsular antigen genes; the aerobactin genes; and the regulator of mucoid phenotype gene, rmpA (156). A recent study demonstrated that ST258 is nonvirulent in animal models, is highly susceptible to serum killing, and can rapidly undergo phagocytosis (156).…”

First Report of Chronic Pulmonary Infection by KPC-3-Producing and Colistin-Resistant Klebsiella pneumoniae Sequence Type 258 (ST258) in an Adult Patient with Cystic Fibrosis

“…However, it should be noted that enhanced virulence might be unnecessary for KPC-producing K. pneumoniae to cause disease. Indeed, despite showing a low virulence in animal models, the widespread ST258 clone is a well-known cause of infection in hospitalized patients, even in subjects without a severe degree of immunodeficiency (15)(16)(17).…”