Infection With Pseudomonas Cepacia In Chronic Granulomatous Disease: Role Of Nonoxidative Killing By Neutrophils In Host Defense

Abstract

Pseudomonas aeruginosa and Pseudomonas cepacia are catalase-producing bacteria, but only P. cepacia causes infections in patients with chronic granulomatous disease (CGD). The in vitro killing of P. aeruginosa and P. cepacia by polymorphonuclear leukocytes (PMNL) from patients with CGD and from healthy adults was assessed. Of 6 patients with CGD who developed severe infections with P. cepacia, 4 died. PMNL from the 2 survivors and 6 other patients with CGD killed P. aeruginosa strains efficiently and P. cepacia strains poorly. PMNL from 2 patients with autosomal recessive CGD and from 2 carriers for X-linked CGD killed P. cepacia intermediately between normal controls and patients with X-linked CGD. When superoxide anion and hydrogen peroxide were scavenged with superoxide dismutase and catalase, normal PMNL killed P. aeruginosa but not P. cepacia. Thus, P. cepacia, but not P. aeruginosa, is a pathogen in patients with CGD, because it resists neutrophil-mediated nonoxidative bactericidal effects.

Invasion of murine respiratory epithelial cells in vivo by Burkholderia cepacia

“…Furthermore, the pathogenic potential of B. cepacia for non-CF patients has been illustrated in patients with chronic granulomatous disease. These patients are unable to kill B. cepacia via oxidative means, and thus they are at risk for infection with B. cepacia which resists non-oxidative killing [28]. Bacteraemic spread (from the lungs) has been observed in these patients (Speert, unpublished data).…”

Burkholderia cepacia: medical, taxonomic and ecological issues

“…However, catalase is associated with the organism's ability to resist killing by professional phagocytes and to produce serious infection in patients with CGD [85]. [90], but the significance of limited epithelial invasion by bacteria remains unclear [9 1 3.…”

In vitro resistance of Burkholderia cepacia complex isolates to reactive oxygen species in relation to catalase and superoxide dismutase production

“…Alternatively, other conditions of stress, including tissue inflammation, may stimulate a bacterial response similar to that of stationary phase and induce a high level of expression of these enzymes. The susceptibility of B. cepacia to oxidative killing is suggested by the observation that neutrophils from CGD patients fail to inactivate B. cepacia (Speert et al, 1994). However, this conclusion contrasts with the apparent tolerance of B. cepacia to the highly oxidative environment in the CF lung, where the inflammatory response is dominated by neutrophils.…”

“…Over the past 20 years the bacterium has emerged as an important opportunistic pathogen, primarily in chronic granulomatous disease (CGD) and cystic fibrosis (CF) patients (Burkholder, 1950 ;Govan & Deretic, 1996 ;Govan & Vandamme, 1998). CGD is a rare genetic disorder (Xlinked or autosomal recessive) resulting in a defect in the oxidative killing mechanism of phagocytic cells, thus making them unable to generate the toxic oxygen metabolites normally involved in inactivating engulfed bacteria (Cline, 1975 ;Speert et al, 1994). These cells still retain their non-oxidative bactericidal activities, mainly through the functions of defensins as well as other bactericidal cationic peptides and proteins (Odell & Segal, 1991).…”

“…Survival within professional phagocytes suggests that B. cepacia may avoid the bactericidal mechanisms employed by these cells. B. cepacia strains demonstrate resistance to non-oxidative killing pathways, as they are able to survive in the presence of neutrophils from CGD patients while the micro-organisms are killed by neutrophils of normal individuals (Speert et al, 1994). During colonization and infection of the airways in CF patients, there is a pronounced inflammatory response that results in the release of toxic oxygen and toxic nitrogen compounds (Bals et al, 1999).…”