Stenotrophomonas maltophiliaouter membrane vesicles elicit a potent inflammatory responsein vitroandin vivo

Abstract

Stenotrophomonas maltophilia has become one of the most prevalent opportunistic pathogens in hospitalized patients. This microorganism secretes outer membrane vesicles (OMVs), but the pathogenesis of S. maltophilia as it relates to OMVs has not been characterized. This study investigated the cytotoxic activity of S. maltophilia OMVs and their ability to induce inflammatory responses both in vitro and in vivo Stenotrophomonas maltophilia ATCC 13637 and two clinical isolates were found to secrete spherical OMVs during in vitro culture. OMVs from S. maltophilia ATCC 13637 were cytotoxic to human lung epithelial A549 cells. Stenotrophomonas maltophilia OMVs stimulated the expression of proinflammatory cytokine and chemokine genes, including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α and monocyte chemoattractant protein-1, in A549 cells. Early inflammatory responses such as congestion and neutrophilic infiltrations and profound expression of proinflammatory cytokine and chemokine genes were observed in the lungs of mice injected with S. maltophilia OMVs, and were similar to responses elicited by the bacteria. Our data demonstrate that S. maltophilia OMVs are important secretory nanocomplexes that elicit a potent inflammatory response that might contribute to S. maltophilia pathogenesis during infection.

Outer membrane vesicles produced by Burkholderia cepacia cultured with subinhibitory concentrations of ceftazidime enhance pro-inflammatory responses

“…OMVs (5 μg/mL) derived from B. pseudomallei did not induce cytotoxicity in murine macrophages [48]. Although host cell death induced by OMVs derived from different Gram-negative, non-fermenting bacterial species was highly dependent on cell type, cytotoxic concentrations of OMVs were all found to be 15 or 20 μg/mL protein concentrations [38,46,47]. Thus, cytotoxic activity of B. cepacia OMVs/LB did not vary significantly from that of OMVs from other Gram-negative non-fermenting bacteria.…”

“…B. cepacia ATCC 25416 OMVs (≥10 μg/mL) obtained from control conditions (no antibiotics) did exert cytotoxic effects on A549 cells ( Figures 2(a ) and 4 ). OMVs derived from Gram-negative, non-fermenting bacteria, including P. aeruginosa, Acinetobacter baumannii, Acinetobacter nosocomialis , and Stenotrophomonas maltophilia , were also shown to induce cytotoxicity in epithelial cells in vitro [ 38 , 45 – 47 ]. OMVs (5 μg/mL) derived from B. pseudomallei did not induce cytotoxicity in murine macrophages [ 48 ].…”

“…OMVs derived from Gram-negative, non-fermenting, opportunistic pathogens, including A. baumannii, A. nosocomialis, P. aeruginosa , and S. maltophilia , stimulate the expression of pro-inflammatory cytokine genes in cultured epithelial cells [ 38 , 41 , 45 – 47 ]. Pulmonary inflammation was also observed in mice administered A. baumannii and S. maltophilia OMVs [ 41 , 47 ]. These data suggest that OMVs derived from Gram-negative, non-fermenting pathogens are a potent stimulator of inflammatory responsesboth in vitro and in vivo .…”

Fatal Neutropenic Enterocolitis Caused by <i>Stenotrophomonas maltophilia</i>: A Rare and Underrecognized Entity

“…S. maltophilia is known to produce extracellular enzymes, such as deoxyribonuclease, ribonuclease, fibrinolysin, lipases, hyaluronidase, protease, and elastase, which may contribute to the pathogenesis of S. maltophilia infection (1). Despite the limited data on S. maltophilia (16), a recent report also reviewed outer membrane vesicles of Gram-negative bacteria and the associated functions, including tissue invasion (17). These virulence factors may play a role in the pathogenesis of hemorrhagic enterocolitis due to S. maltophilia in addition to the aforementioned risk factors and severely immunosuppressive conditions.…”

The Contribution of Membrane Vesicles to Bacterial Pathogenicity in Cystic Fibrosis Infections and Healthcare Associated Pneumonia

“…Regarding to this, N-acetyl-L-cysteine (NAC), a mucolytic that reduces the production of thick mucus, induced the release of pro-inflammatory MVs by these respiratory pathogens, but decreased the release of proinflammatory cytokines in macrophages (Volgers et al, 2017a). Moreover, MVs secreted by S. maltophilia ATCC 13637 were cytotoxic to A549 epithelial cells and induced the expression of pro-inflammatory cytokine and chemokine genes in these lung cells (Kim et al, 2016). MVs originated from K. pneumoniae ATCC 13883 likewise induced changes in the expression of immune-related genes in epithelial cells.…”