scholarly journals Pneumocystis carinii Interactions with Lung Epithelial Cells and Matrix Proteins Induce Expression and Activity of the PcSte20 Kinase with Subsequent Phosphorylation of the Downstream Cell Wall Biosynthesis Kinase PcCbk1

2011 ◽  
Vol 79 (10) ◽  
pp. 4157-4164 ◽  
Author(s):  
Theodore J. Kottom ◽  
Joshua W. Burgess ◽  
Andrew H. Limper
Keyword(s):  
Cell Wall ◽  
Epithelial Cells ◽  
Fungal Pathogen ◽  
Pneumocystis Carinii ◽  
Specific Region ◽  
Lung Epithelial Cells ◽  
Matrix Proteins ◽  
Content Type ◽  
Lung Epithelial ◽  
Opportunistic Fungal Pathogen

ABSTRACTEukaryotic cell proliferation and phenotype are highly regulated by contact-dependent mechanisms. We have previously shown that the binding and interaction of the opportunistic fungal pathogenPneumocystis cariniito lung epithelial cells and extracellular matrix proteins induces mRNA expression of both the mitogen-activated protein (MAP) kinaseP. cariniiSte20 (PcSte20) and the cell wall-remodeling enzymePcCbk1(16). Herein, we report that in addition toPcSte20mRNA expression being upregulated,PneumocystisPcSte20 kinase activity is increased upon interacting with these same lung targets. This activity is also significantly suppressed byClostridium difficiletoxin B, a pan-specific inhibitor of small GTPases, demonstrating the potential role of a Cdc42-like molecule in this signaling cascade. We further observed that the PcSte20 kinase physically interacts with a specific region of theP. cariniicell wall biosynthesis kinase, PcCbk1, a downstream kinase important for mating projection formation and cell wall remodeling. This direct binding was mapped to a specific region of the PcCbk1 protein. We also demonstrated that PcSte20 obtained from wholeP. cariniilysates has the ability to phosphorylate PcCbk1 after the organism interacts with lung epithelial cells and extracellular matrix components. These observations provide new insights intoP. cariniisignaling induced by interactions of this important opportunistic fungal pathogen with lung epithelial cells and matrix.

scholarly journals Interactions of an Emerging Fungal Pathogen Scedosporium aurantiacum with Human Lung Epithelial Cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jashanpreet Kaur ◽  
Liisa Kautto ◽  
Anahit Penesyan ◽  
Wieland Meyer ◽  
Liam D. H. Elbourne ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Fungal Pathogen ◽  
Human Lung ◽  
Lung Epithelial Cells ◽  
Lung Epithelial ◽  
Human Lung Epithelial Cells

scholarly journals Cell Wall Chitosan Is Necessary for Virulence in the Opportunistic Pathogen Cryptococcus neoformans

2011 ◽  
Vol 10 (9) ◽  
pp. 1264-1268 ◽  
Author(s):  
Lorina G. Baker ◽  
Charles A. Specht ◽  
Jennifer K. Lodge
Keyword(s):  
Cell Wall ◽  
Cryptococcus Neoformans ◽  
Fungal Pathogen ◽  
Slow Growth ◽  
Opportunistic Pathogen ◽  
Mammalian Host ◽  
Cell Integrity ◽  
Content Type ◽  
Opportunistic Fungal Pathogen ◽  
Chitin And Chitosan

ABSTRACTCryptococcus neoformansis an opportunistic fungal pathogen that causes meningoencephalitis. Its cell wall is composed of glucans, proteins, chitin, and chitosan. Multiple genetic approaches have defined a chitosan-deficient syndrome that includes slow growth and decreased cell integrity. Here we demonstrate chitosan is necessary for virulence and persistence in the mammalian host.

scholarly journals Linocin and OmpW Are Involved in Attachment of the Cystic Fibrosis-Associated Pathogen Burkholderia cepacia Complex to Lung Epithelial Cells and Protect Mice against Infection

2016 ◽  
Vol 84 (5) ◽  
pp. 1424-1437 ◽  
Author(s):  
Siobhán McClean ◽  
Marc E. Healy ◽  
Cassandra Collins ◽  
Stephen Carberry ◽  
Luke O'Shaughnessy ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Burkholderia Cepacia ◽  
Therapeutic Option ◽  
Lung Epithelial Cells ◽  
Burkholderia Cenocepacia ◽  
Burkholderia Cepacia Complex ◽  
Content Type ◽  
Lung Epithelial ◽  
Proteomics Approach

Members of theBurkholderia cepaciacomplex (Bcc) cause chronic opportunistic lung infections in people with cystic fibrosis (CF), resulting in a gradual lung function decline and, ultimately, patient death. The Bcc is a complex of 20 species and is rarely eradicated once a patient is colonized; therefore, vaccination may represent a better therapeutic option. We developed a new proteomics approach to identify bacterial proteins that are involved in the attachment of Bcc bacteria to lung epithelial cells. Fourteen proteins were reproducibly identified by two-dimensional gel electrophoresis from four Bcc strains representative of two Bcc species:Burkholderia cenocepacia, the most virulent, andB. multivorans, the most frequently acquired. Seven proteins were identified in both species, but only two were common to all four strains, linocin and OmpW. Both proteins were selected based on previously reported data on these proteins in other species.Escherichia colistrains expressing recombinant linocin and OmpW showed enhanced attachment (4.2- and 3.9-fold) to lung cells compared to the control, confirming that both proteins are involved in host cell attachment. Immunoproteomic analysis using serum from Bcc-colonized CF patients confirmed that both proteins elicit potent humoral responsesin vivo. Mice immunized with either recombinant linocin or OmpW were protected fromB. cenocepaciaandB. multivoranschallenge. Both antigens induced potent antigen-specific antibody responses and stimulated strong cytokine responses. In conclusion, our approach identified adhesins that induced excellent protection against two Bcc species and are promising vaccine candidates for a multisubunit vaccine. Furthermore, this study highlights the potential of our proteomics approach to identify potent antigens against other difficult pathogens.

scholarly journals Lung Epithelial Cells and Extracellular Matrix Components Induce Expression of Pneumocystis carinii STE20, a Gene Complementing the Mating and Pseudohyphal Growth Defects of ste20 Mutant Yeast

2003 ◽  
Vol 71 (11) ◽  
pp. 6463-6471 ◽  
Author(s):  
Theodore J. Kottom ◽  
Julia R. Köhler ◽  
Charles F. Thomas ◽  
Gerald R. Fink ◽  
Andrew H. Limper
Keyword(s):  
Extracellular Matrix ◽  
Epithelial Cells ◽  
Matrix Protein ◽  
Pneumocystis Carinii ◽  
Lung Epithelial Cells ◽  
Central Feature ◽  
Pseudohyphal Growth ◽  
Extracellular Matrix Components ◽  
Lung Epithelial ◽  
Immunocompromised Hosts

ABSTRACT Pneumocystis carinii causes severe pneumonia in immunocompromised hosts. The binding of P. carinii to alveolar epithelial cells and extracellular matrix constituents such as fibronectin and vitronectin is a central feature of infection, which initiates proliferation of the organism. Herein, we demonstrate that P. carinii binding to lung cells specifically alters the gene expression of the organism, regulating fungal growth. Subtractive hybridization was performed to isolate P. carinii genes expressed following binding to mammalian extracellular matrix constituents. P. carinii STE20 (PCSTE20), a gene participating in mating and pseudohyphal growth of other fungi, was identified following adherence to the extracellular matrix constituents fibronectin, vitronectin, collagen, and lung epithelial cells. The expression of PCSTE20 and a related P. carinii mitogen-activated protein kinase (MAPK) kinase gene, also implicated in signaling of mating, were both specifically upregulated by binding to matrix protein. The expression of general cyclin-dependent kinases and other MAPKs not involved in mating pathways were not altered by organism binding. PCSTE20 expression was also strongly enhanced following organism attachment to A549 lung epithelial cells. When expressed in a Saccharomyces cerevisiae ste20Δ mutant, PCSTE20 suppressed defects in both mating and pseudohyphal growth. These findings are consistent with the observed proliferation and filopodial extension of Pneumocystis organisms adherent to the epithelium in the lungs of immunocompromised hosts. PCSTE20 expression appears to represent a significant component in the regulation of the life cycle of this intractable opportunistic pathogen.

scholarly journals Lcl of Legionella pneumophila Is an Immunogenic GAG Binding Adhesin That Promotes Interactions with Lung Epithelial Cells and Plays a Crucial Role in Biofilm Formation

2011 ◽  
Vol 79 (6) ◽  
pp. 2168-2181 ◽  
Author(s):  
Carla Duncan ◽  
Akriti Prashar ◽  
Jannice So ◽  
Patrick Tang ◽  
Donald E. Low ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Legionella Pneumophila ◽  
Biofilm Formation ◽  
Case Fatality ◽  
Lung Epithelial Cells ◽  
Molecular Evidence ◽  
Heparin Binding ◽  
Content Type ◽  
Lung Epithelial

ABSTRACTLegionellosis is mostly caused byLegionella pneumophilaand is defined by a severe respiratory illness with a case fatality rate ranging from 5 to 80%.In vitroandin vivo, interactions ofL. pneumophilawith lung epithelial cells are mediated by the sulfated glycosaminoglycans (GAGs) of the host extracellular matrix. In this study, we have identified severalLegionellaheparin binding proteins. We have shown that one of these proteins, designated Lcl, is a polymorphic adhesin ofL. pneumophilathat is produced during legionellosis. Homologues of Lcl are ubiquitous inL. pneumophilaserogroups but are undetected in otherLegionellaspecies. Recombinant Lcl binds to GAGs, and a Δlpg2644mutant demonstrated reduced binding to GAGs and human lung epithelial cells. Importantly, we showed that the Δlpg2644strain is dramatically impaired in biofilm formation. These data delineate the role of Lcl in the GAG binding properties ofL. pneumophilaand provide molecular evidence regarding its role inL. pneumophilaadherence and biofilm formation.

scholarly journals Stenotrophomonas maltophiliaEncodes a VirB/VirD4 Type IV Secretion System That Modulates Apoptosis in Human Cells and Promotes Competition against Heterologous Bacteria, IncludingPseudomonas aeruginosa

2019 ◽  
Vol 87 (9) ◽  
Author(s):  
Megan Y. Nas ◽  
Richard C. White ◽  
Ashley L. DuMont ◽  
Alberto E. Lopez ◽  
Nicholas P. Cianciotto
Keyword(s):  
Epithelial Cells ◽  
Mammalian Cells ◽  
Secretion System ◽  
Lung Epithelial Cells ◽  
Type Ii Secretion ◽  
Bacterial Cells ◽  
Content Type ◽  
Type Iv ◽  
Lung Epithelial ◽  
Induced Apoptosis

ABSTRACTStenotrophomonas maltophiliais an emerging opportunistic and nosocomial pathogen.S. maltophiliais also a risk factor for lung exacerbations in cystic fibrosis patients.S. maltophiliaattaches to various mammalian cells, and we recently documented that the bacterium encodes a type II secretion system which triggers detachment-induced apoptosis in lung epithelial cells. We have now confirmed thatS. maltophiliaalso encodes a type IVA secretion system (VirB/VirD4 [VirB/D4] T4SS) that is highly conserved amongS. maltophiliastrains and, looking beyond theStenotrophomonasgenus, is most similar to the T4SS ofXanthomonas. To define the role(s) of this T4SS, we constructed a mutant of strain K279a that is devoid of secretion activity due to loss of the VirB10 component. The mutant induced a higher level of apoptosis upon infection of human lung epithelial cells, indicating that a T4SS effector(s) has antiapoptotic activity. However, when we infected human macrophages, the mutant triggered a lower level of apoptosis, implying that the T4SS also elaborates a proapoptotic factor(s). Moreover, when we cocultured K279a with strains ofPseudomonas aeruginosa, the T4SS promoted the growth ofS. maltophiliaand reduced the numbers of heterologous bacteria, signaling that another effector(s) has antibacterial activity. In all cases, the effect of the T4SS requiredS. maltophiliacontact with its target. Thus,S. maltophiliaVirB/D4 T4SS appears to secrete multiple effectors capable of modulating death pathways. That a T4SS can have anti- and prokilling effects on different targets, including both human and bacterial cells, has, to our knowledge, not been seen before.

scholarly journals Candida albicans ENT2 Contributes to Efficient Endocytosis, Cell Wall Integrity, Filamentation, and Virulence

mSphere ◽  
2021 ◽  
Author(s):  
Christiane Rollenhagen ◽  
Harrison Agyeman ◽  
Susan Eszterhas ◽  
Samuel A. Lee
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Fungal Pathogen ◽  
Clinical Importance ◽  
Hospitalized Patients ◽  
Cell Wall Integrity ◽  
Content Type ◽  
Invasive Infections ◽  
Opportunistic Fungal Pathogen ◽  
Considerable Morbidity

The opportunistic fungal pathogen Candida albicans is an important cause of invasive infections in hospitalized patients and a source of considerable morbidity and mortality. Despite its clinical importance, we still need to improve our ability to diagnose and treat this common pathogen.

Histoplasma capsulatum chemotypes I and II induce IL-8 secretion in lung epithelial cells in distinct manners

2020 ◽  
Vol 58 (8) ◽  
pp. 1169-1177 ◽  
Author(s):  
Cristiane Alcantara ◽  
Bruna Rocha Almeida ◽  
Bianca Carla Silva Campitelli Barros ◽  
Cristina Mary Orikaza ◽  
Marcos Sergio Toledo ◽  
...  
Keyword(s):  
Cell Wall ◽  
Epithelial Cells ◽  
Cell Cultures ◽  
A549 Cell ◽  
Histoplasma Capsulatum ◽  
Specific Inhibitor ◽  
Lung Epithelial Cells ◽  
Wild Type ◽  
Lung Epithelial ◽  
Spontaneous Variant

Abstract The cell wall is one of the most important structures of pathogenic fungi, enabling initial interaction with the host and consequent modulation of immunological responses. Over the years, some researchers have shown that cell wall components of Histoplasma capsulatum vary among fungal isolates, and one of the major differences is the presence or absence of α-(1,3)-glucan, classifying wild-type fungi as chemotypes II or I, respectively. The present work shows that an isolate of H. capsulatum chemotype I induced lower levels of interleukin (IL)-8 secretion by the lung epithelial cell line A549, when compared to chemotype II yeasts. Thus, we expected that the absence of α-glucan in spontaneous variant yeasts, which were isolated from chemotype II cultures, would modify IL-8 secretion by A549 cells, but surprisingly, these fungi promoted similar levels of IL-8 secretion as their wild-type counterpart. Furthermore, when using a specific inhibitor for Syk activation, we observed that this inhibitor reduced IL-8 levels in A549 cell cultures infected with wild type chemotype I fungi. This inhibitor failed to reduce this cytokine levels in A549 cell cultures infected with chemotype II and their spontaneous variant yeasts, which also do not present α-glucan on their surface. The importance of SFKs and PKC δ in this event was also analyzed. Our results show that different isolates of H. capsulatum modulate distinct cell signaling pathways to promote cytokine secretion in host epithelial cells, emphasizing the existence of various mechanisms for Histoplasma pathogenicity.

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