Molecular Characterization of Virulence Determinants of <i>Stenotrophomonas Maltophilia</i> Strains Isolated from Patients Affected by Cystic Fibrosis

Bonaventura, Giovanni Di; Prosseda, Gianni; Chierico, Federica Del; Cannavacciuolo, Sonia; Cipriani, Paola; Petrucca, Andrea; Superti, Fabiana; Ammendolia, Maria Grazia; Concato, Carlo; Fiscarelli, Ersilia; Casalino, Mariassunta; Piccolomini, R; Nicoletti, Mauro; Colonna, Bianca

doi:10.1177/039463200702000311

Cited by 48 publications

(50 citation statements)

References 18 publications

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“…Recently, we showed that S. maltophilia is able to invade cultured A549 respiratory epithelial cells, although at very low levels (18). The results from the present study confirm the scant invasiveness of S. maltophilia, as suggested by a transient and minimal presence of the microorganism in the spleens of DBA/2 mice.…”

Section: Discussionsupporting

confidence: 87%

Role of Excessive Inflammatory Response to Stenotrophomonas maltophilia Lung Infection in DBA/2 Mice and Implications for Cystic Fibrosis

et al. 2010

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Stenotrophomonas maltophilia is a pathogen that causes infections mainly in immunocompromised patients. Despite increased S. maltophilia isolation from respiratory specimens of patients with cystic fibrosis (CF), the real contribution of the microorganism to CF pathogenesis still needs to be clarified. The aim of the present study was to evaluate the pathogenic role of S. maltophilia in CF patients by using a model of acute respiratory infection in DBA/2 mice following a single exposure to aerosolized bacteria. The pulmonary bacterial load was stable until day 3 and then decreased significantly from day 3 through day 14, when the bacterial load became undetectable in all infected mice. Infection disseminated in most mice, although at a very low level. Severe effects (swollen lungs, large atelectasis, pleural adhesion, and hemorrhages) of lung pathology were observed on days 3, 7, and 14. The clearance of S. maltophilia observed in DBA/2 mouse lungs was clearly associated with an early and intense bronchial and alveolar inflammatory response, which is mediated primarily by neutrophils. Significantly higher levels of interleukin-1␤ (IL-1␤), IL-6, IL-12, gamma interferon (IFN-␥), tumor necrosis factor alpha (TNF-␣), GRO␣/KC, MCP-1/JE, MCP-5, macrophage inflammatory protein 1␣ (MIP-1␣), MIP-2, and TARC were observed in infected mice on day 1 with respect to controls. Excessive pulmonary infection and inflammation caused systemic effects, manifested by weight loss, and finally caused a high mortality rate. Taken together, our results show that S. maltophilia is not just a bystander in CF patients but has the potential to contribute to the inflammatory process that compromises respiratory function.

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Section: Discussionsupporting

confidence: 87%

Role of Excessive Inflammatory Response to Stenotrophomonas maltophilia Lung Infection in DBA/2 Mice and Implications for Cystic Fibrosis

et al. 2010

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“…The fliI mutants caused IB3-1 monolayer cell disruption after 6 h, suggesting that the mutants have increased virulence; further research is needed to explain this altered virulence. Swimming and twitching motilities of S. maltophilia CF isolates did not correlate with adherence or biofilm formation on bronchial cells (88,268). In another study, S. maltophilia CF isolates and two nonrespiratory S. maltophilia reference strains (environmental strain LMG959 and blood-isolated strain K279a) were examined for swimming and twitching motil-ity and biofilm formation; no correlation was observed for biofilm formation and motility (88).…”

Section: Adherence To and Invasion Of Host Cellsmentioning

confidence: 94%

“…The gene encoding the extracellular protease StmPr1 was found in only 2 of 11 S. maltophilia clinical isolates (strains OBGTC9 and OBGTC10, recovered from persistent infections in CF patients), suggesting that the gene may be found in isolates that have been able to cause chronic infections in these patients (88). (225,240).…”

Section: Hydrolytic Enzymesmentioning

confidence: 99%

Stenotrophomonas maltophilia: an Emerging Global Opportunistic Pathogen

2012

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SUMMARY Stenotrophomonas maltophilia is an emerging multidrug-resistant global opportunistic pathogen. The increasing incidence of nosocomial and community-acquired S. maltophilia infections is of particular concern for immunocompromised individuals, as this bacterial pathogen is associated with a significant fatality/case ratio. S. maltophilia is an environmental bacterium found in aqueous habitats, including plant rhizospheres, animals, foods, and water sources. Infections of S. maltophilia can occur in a range of organs and tissues; the organism is commonly found in respiratory tract infections. This review summarizes the current literature and presents S. maltophilia as an organism with various molecular mechanisms used for colonization and infection. S. maltophilia can be recovered from polymicrobial infections, most notably from the respiratory tract of cystic fibrosis patients, as a cocolonizer with Pseudomonas aeruginosa . Recent evidence of cell-cell communication between these pathogens has implications for the development of novel pharmacological therapies. Animal models of S. maltophilia infection have provided useful information about the type of host immune response induced by this opportunistic pathogen. Current and emerging treatments for patients infected with S. maltophilia are discussed.

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“…Early on, it was determined that a bronchial isolate of S. maltophilia secretes a 47-kDa serine protease (StmPr1) that, when purified from the bacterial culture supernatant, can cause rounding of human fibroblasts (32). Subsequent genomic analysis revealed that strain K279a carries the stmPr1 gene (SMLT_RS03270) (18,19,33), and it is now apparent that stmPr1 maps directly The A549, HeLa, MLE, and 3T3 cell lines were incubated for 3 h with 25% (vol/vol) supernatants from strain K279a (WT), the xpsF mutant NUS4 (xpsF), the complemented xpsF mutant (xpsF/pxpsF), or a medium control. Mammalian cell morphology was evaluated by phase-contrast light microscopy.…”

Section: Xps T2s Causes Rounding and Detachment Of Epithelial And Fibmentioning

confidence: 99%

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

2015

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Stenotrophomonas maltophilia is an emerging opportunistic pathogen that primarily causes pneumonia and bacteremia in immunocompromised individuals. We recently reported that S. maltophilia strain K279a encodes the Xps type II secretion system and that Xps promotes rounding, actin rearrangement, detachment, and death in the human lung epithelial cell line A549. Here, we show that Xps-dependent cell rounding and detachment occur with multiple human and murine cell lines and that serine protease inhibitors block Xps-mediated rounding and detachment of A549 cells. Using genetic analysis, we determined that the serine proteases StmPr1 and StmPr2, which were confirmed to be Xps substrates, are predominantly responsible for secreted proteolytic activities exhibited by strain K279a, as well as the morphological and cytotoxic effects on A549 cells. Supernatants from strain K279a also promoted the degradation of type I collagen, fibrinogen, and fibronectin in a predominantly Xps-and protease-dependent manner, although some Xps-independent degradation of fibrinogen was observed. Finally, Xps, and predominantly StmPr1, degraded interleukin 8 (IL-8) secreted by A549 cells during coculture with strain K279a. Our findings indicate that while StmPr1 and StmPr2 are predominantly responsible for A549 cell rounding, extracellular matrix protein degradation, and IL-8 degradation, additional Xps substrates also contribute to these activities. Altogether, our data provide new insight into the virulence potential of the S. maltophilia Xps type II secretion system and its StmPr1 and StmPr2 substrates. The Gram-negative bacterium Stenotrophomonas maltophilia, prevalent in the aqueous environment, is now emerging as a prominent opportunistic and nosocomial pathogen (1, 2). S. maltophilia infects an array of host tissues and organs, including the respiratory tract, blood, bone, soft tissue, eye, urinary tract, heart, and brain. However, pneumonia is the most common infection associated with S. maltophilia, followed by bloodstream infection as the second most common (1, 2). S. maltophilia, though relatively nonvirulent for healthy individuals, can cause serious infection in immunocompromised individuals. Therefore, S. maltophilia poses the biggest threat for patients with severe burns, cystic fibrosis, and HIV, as well as those undergoing chemotherapy or immunosuppressive therapy (3). Prolonged hospitalization in intensive care units and long-term antibiotic treatment are also considered risk factors for developing pneumonia and bacteremia, for which mortality rates can range from 23 to 77% and 14 to 69%, respectively (1, 4). Community-acquired S. maltophilia infections, especially in the high-risk populations mentioned, have been reported (5), and recently, a communityacquired skin infection was reported for the first time in an immunocompetent individual (6). 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 trimeth...

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Molecular Characterization of Virulence Determinants of Stenotrophomonas Maltophilia Strains Isolated from Patients Affected by Cystic Fibrosis

Cited by 48 publications

References 18 publications

Role of Excessive Inflammatory Response to Stenotrophomonas maltophilia Lung Infection in DBA/2 Mice and Implications for Cystic Fibrosis

Role of Excessive Inflammatory Response to Stenotrophomonas maltophilia Lung Infection in DBA/2 Mice and Implications for Cystic Fibrosis

Stenotrophomonas maltophilia: an Emerging Global Opportunistic Pathogen

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

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