Stenotrophomonas maltophilia strains from cystic fibrosis patients: Genomic variability and molecular characterization of some virulence determinants

Nicoletti, Mauro; Iacobino, Angelo; Prosseda, Gianni; Fiscarelli, Ersilia; Zarrilli, Raffaele; Carolis, Elena De; Petrucca, Andrea; Nencioni, Lucia; Colonna, Bianca; Casalino, Maria Assunta

doi:10.1016/j.ijmm.2010.07.003

Cited by 63 publications

(59 citation statements)

References 45 publications

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“…S3B in the supplemental material). Looking beyond the sequenced genomes, the presence of both stmPr1 and stmPr2 was confirmed by PCR analysis in the majority of cystic fibrosis clinical isolates, and strain K279a stmPr1 is the most common allelic variant of stmPr1 among these isolates (18). The conservation of stmPr1 and stmPr2 among clinical isolates, together with our experimental data, suggests roles for StmPr1 and StmPr2 in the virulence of S. maltophilia.…”

Section: Discussionsupporting

confidence: 65%

“…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%

“…2B). Interestingly, strain K279a also carries the gene for a second serine protease, StmPr2, (SMLT_RS04110), which, like StmPr1, is a member of the S8 peptidase family (18). In the strain K279a genome, the stmPr2 gene is found approximately 200 kb from stmPr1 (Fig.…”

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

confidence: 99%

“…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).…”

mentioning

confidence: 99%

“…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).…”

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confidence: 99%

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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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Section: Discussionsupporting

confidence: 65%

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

confidence: 99%

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

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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

2015

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Bacteria from Ips sexdentatus (Coleoptera: Curculionidae) and their biocontrol potential

Sevim

Gökçe

Erbaş

et al. 2012

J. Basic Microbiol.

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Ips sexdentatus (Coleoptera: Curculionidae) is one of the most destructive pests of the spruce trees in Europe. In this study, we have isolated and characterized culturable bacteria from I. sexdentatus and tested their insecticidal activity against the last instar larvae of the pest as a possible biocontrol agent. A total of eight bacterial isolates was determined and four of them were identified at species level, and the others were identified at genus level. Isolates were identified as Stenotrophomonas maltophilia (Is1), Rahnella sp. (Is2), Pseudomonas sp. (Is3), Bacillus sp. (Is4), Alcaligenes faecalis (Is5), Panteoea agglomerans (Is6), Pseudomonas fluorescens (Is7) and Serratia sp. (Is8) based on their morphological, biochemical and molecular characteristics. Insecticidal effects of bacterial isolates were performed on the last instar larvae of the pest. The highest insecticidal activity was obtained from P. fluorescens (Is7) with 73% mortality within 10 days after inoculation (p < 0.05). Mortality values of the other isolates ranged from 20 to 53%. This study suggests that Pseudomonas fluorescens (Is7) seems to be a good candidate as a possible biocontrol agent against I. sexdentatus, and provides suitable strains that can be modified to express insecticidal toxins and/or other detrimental substances to develop new control methods for I. sexdentatus.

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Utility of Insects for Studying Human Pathogens and Evaluating New Antimicrobial Agents

Wang

Jiang

et al. 2013

Advances in Biochemical Engineering/Biotechnology

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Insect models, such as Galleria mellonella and Drosophila melanogaster have significant ethical, logistical, and economic advantages over mammalian models for the studies of infectious diseases. Using these models, various pathogenic microbes have been studied and many novel virulence genes have been identified. Notably, because insects are susceptible to a wide variety of human pathogens and have immune responses similar to those of mammals, they offer the opportunity to understand innate immune responses against human pathogens better. It is important to note that insect pathosystems have also offered a simple strategy to evaluate the efficacy and toxicity of many antimicrobial agents. Overall, insect models provide a rapid, inexpensive, and reliable way as complementary hosts to conventional vertebrate animal models to study pathogenesis and antimicrobial agents.

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Stenotrophomonas maltophilia strains from cystic fibrosis patients: Genomic variability and molecular characterization of some virulence determinants

Cited by 63 publications

References 45 publications

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

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

Bacteria from Ips sexdentatus (Coleoptera: Curculionidae) and their biocontrol potential

Utility of Insects for Studying Human Pathogens and Evaluating New Antimicrobial Agents

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