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

Abstract

The environmental bacterium Stenotrophomonas maltophilia is increasingly described as a multidrug-resistant pathogen of humans, being associated with pneumonia, among other diseases. But the degree to which S. maltophilia is capable of replicating in a mammalian host has been an issue of controversy. Using a model of intranasal inoculation into adult A/J mice, we now document that S. maltophilia strain K279a, the clinical isolate of S. maltophilia whose complete genome sequence was recently determined, is in fact capable of replicating in lungs, displaying as much as a 10-fold increase in c.f.u. in the first 8 h of infection. Importantly, as few as 104 c.f.u. deposited into the A/J lung was sufficient to promote bacterial outgrowth. Bacterial replication in the lungs of the A/J mice was followed by elevations in pro-inflammatory cytokines and also promoted resistance to subsequent challenge. We also found that DBA/2 mice were permissive for S. maltophilia K279a replication, although the level of growth and persistence in these animals was less than it was in the A/J mice. In contrast, the BALB/c and C57BL/6 mouse strains were non-permissive for S. maltophilia K279a growth. Interestingly, when five additional clinical isolates were introduced into the A/J lung, marked differences in survival were observed, with some strains being much less infective than K279a and others being appreciably more infective. These data suggest that the presence of major virulence determinants is variable among clinical isolates. Overall, this study confirms the infectivity of S. maltophilia for the mammalian host, and illustrates how both host and bacterial factors affect the outcome of Stenotrophomonas infection.

Functional Characterization of the RNA Chaperone Hfq in the Opportunistic Human Pathogen Stenotrophomonas maltophilia

“…In fact, different mouse strains can be either permissive or nonpermissive for the replication of S. maltophilia (34). Based on our dRNA-seq, 63 genes were found to be differentially expressed in wild-type and mutant cells (Table 2) and are potentially regulated directly or indirectly by Hfq.…”

“…S. maltophilia is frequently isolated from the lungs of cystic fibrosis patients, and its multidrug-resistant phenotype complicates the eradication of S. maltophilia infections (35). Factors that may contribute to the pathogenicity of S. maltophilia include a wide range of extracellular enzymes potentially involved in the colonization process, such as fibrolysin, lipases, and proteases (6), the ability to adhere to and form biofilms on epithelial cells (31), and replication and persistence in the lung (34). Deterioration of lung function associated with S. maltophilia infections has been demonstrated by infection assays carried out in mice (10).…”

Stenotrophomonas maltophilia Encodes a Type II Protein Secretion System That Promotes Detrimental Effects on Lung Epithelial Cells

“…Phenotyping of S. maltophilia strains suggests that the organism has traits that are linked to the virulence of other bacteria (3,5). Inoculation of S. maltophilia into the lungs of mice results in bacterial replication and a marked inflammatory response (9)(10)(11). However, documentation of the genetic basis of S. maltophilia pathogenicity is in its infancy.…”

Type II Secretion-Dependent Degradative and Cytotoxic Activities Mediated by Stenotrophomonas maltophilia Serine Proteases StmPr1 and StmPr2

“…In the murine lung, S. maltophilia induces inflammation and neutrophil recruitment, and it has been shown to grow and persist in certain mouse strains (11,(13)(14)(15). In all infection models, S. maltophilia strains have displayed various degrees of virulence (13,(15)(16)(17)(18), but the molecular mechanisms mediating S. maltophilia pathogenesis have yet to be determined. The presence of virulence traits that commonly promote infection by other genera have been suggested by the sequenced genome of the clinical isolate K279a, as well as several additional sequenced genomes (19,20).…”

“…The multidrug-resistant nature of S. maltophilia makes treatment of infections highly difficult (7), and in recent years, an increased resistance to the preferred antibiotic trimethoprim-sulfamethoxazole has been reported (8-10). These findings emphasize the need to better understand the virulence mechanisms employed by S. maltophilia.The current understanding of S. maltophilia pathogenesis is limited, although studies have begun to investigate S. maltophilia infection in mammalian and nonmammalian animal models (11)(12)(13)(14)(15)(16)(17)(18). In the murine lung, S. maltophilia induces inflammation and neutrophil recruitment, and it has been shown to grow and persist in certain mouse strains (11,(13)(14)(15).…”