Immunostimulatory Properties of the Emerging Pathogen Stenotrophomonas maltophilia

Abstract

Stenotrophomonas maltophilia is a multiple-antibiotic-resistant opportunistic pathogen that is being isolated with increasing frequency from patients with health-care-associated infections and especially from patients with cystic fibrosis (CF). While clinicians feel compelled to treat infections involving this organism, its potential for virulence is not well established. We evaluated the immunostimulatory properties and overall virulence of clinical isolates of S. maltophilia using the well-characterized opportunistic pathogen Pseudomonas aeruginosa PAO1 as a control. The properties of CF isolates were examined specifically to see if they have a common phenotype. The immunostimulatory properties of S. maltophilia were studied in vitro by stimulating airway epithelial and macrophage cell lines. A neonatal mouse model of pneumonia was used to determine the rates of pneumonia, bacteremia, and mortality, as well as the inflammatory response elicited by S. maltophilia infection. Respiratory and nonrespiratory S. maltophilia isolates were highly immunostimulatory and elicited significant interleukin-8 expression by airway epithelial cells, as well as tumor necrosis factor alpha (TNF-␣) expression by macrophages. TNF-␣ signaling appears to be important in the pathogenesis of S. maltophilia infection as less than 20% of TNFR1 null mice (compared with 100% of wild-type mice) developed pneumonia and bacteremia following intranasal inoculation. The S. maltophilia isolates were weakly invasive, and low-level bacteremia with no mortality was observed. Despite the lack of invasiveness of S. maltophilia, the immunostimulatory properties of this organism and its induction of TNF-␣ expression specifically indicate that it is likely to contribute significantly to airway inflammation.

Stenotrophomonas maltophilia strains replicate and persist in the murine lung, but to significantly different degrees

“…The K279a genome sequence reveals a number of potential virulence factors and immune modulators, based upon the in vivo importance of their homologues in other bacteria (Crossman et al, 2008). These factors include type I, II, IV and V protein secretion systems, tissue-degradative exoenzymes, various pili, putative adhesins, flagella, LPS, putative exopolysaccharide, siderophores and quorum sensing (Crossman et al, 2008;Denton & Kerr, 1998;Fouhy et al, 2007;Huang & Wong, 2007;Looney et al, 2009;Minkwitz & Berg, 2001;Rocco et al, 2009;Travassos et al, 2004;Waters et al, 2007;Zgair & Chhibber, 2010b). Thus, the A/J mouse model can be used to compare wildtype K279a with its mutant derivatives in order to formally define the virulence factors of S. maltophilia.…”

“…7-10-day-old) C57BL/6 mice with different strains of S. maltophilia; but, as noted above, no evidence for bacterial replication was reported after determining lung c.f.u. at 16 h postinoculation (Waters et al, 2007).…”

“…First, S. maltophilia is often isolated from patients along with other bacteria, especially in cases of pneumonia (Ryan et al, 2009). Second, several studies which used a pure culture of S. maltophilia to infect the lungs of mice or rats did not document significant increases in bacterial numbers post-inoculation; rather, bacterial numbers were only reported as declining between days 1 and 7 post-inoculation (Di Bonaventura et al, 2010;George et al, 1993;McKay et al, 2003;Waters et al, 2007). Thus, we sought to more thoroughly address the issue of S. maltophilia infectivity by examining six different strains of S. maltophilia for their ability to replicate and persist in the lungs of four different strains of inbred mice, utilizing various inoculating doses and assaying bacterial numbers at earlier times post-inoculation.…”

“…Limited phenotypic analysis of S. maltophilia strains in vitro and the recent sequencing of the S. maltophilia genome both suggest that the organism has traits that have been linked to the virulence of other bacteria (Crossman et al, 2008;Denton & Kerr, 1998;Looney et al, 2009;Nicoletti et al, 2011;Rocco et al, 2009;Ryan et al, 2009). Also, inoculation of S. maltophilia into the lungs of mice results in a marked inflammatory response within 24 h that involves, among other things, elevated cytokines (Di Bonaventura et al, 2010;Waters et al, 2007;Zgair & Chhibber, 2010a). However, the degree to which S. maltophilia is capable of replicating on its own within a mammalian host has remained a point of some controversy for several reasons.…”

Shifts in bacterial communities of two caribbean reef-building coral species affected by white plague disease

“…Different species of bacteria that have been associated to other organisms were also characterized, including Vibrio rotiferianus associated with normal microbiota of rotifers (Gomez-Gil et al, 2003), and Microbacterium oxydans and Nocardiopsis alba associated with normal microbiota of different insects (Pidiyar et al, 2004;Rudolf et al, 2009;Patil et al, 2010). Other bacterial species involved in nosocomial infections were isolated, such as Stenotrophomonas rhizophila (normally associated with plants) (Wolf et al, 2002) and Stenotrophomonas maltophilia (Waters et al, 2007). Brevibacterium linens was isolated exclusively from WPD-affected corals.…”