scholarly journals Protease activities of vaginal Porphyromonas species disrupt coagulation and extracellular matrix in the cervicovaginal niche

2021 ◽  
Author(s):  
Karen V. Lithgow ◽  
Vienna C.H. Buchholz ◽  
Emily Ku ◽  
Shaelen Konschuh ◽  
Ana D'Aubeterre ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Reproductive Tract ◽  
Type I Collagen ◽  
Structural Integrity ◽  
Opportunistic Pathogen ◽  
Cysteine Proteases ◽  
Female Reproductive Tract ◽  
Cloning And Expression ◽  
Type I ◽  
Human Vagina

Porphyromonas asaccahrolytica and Porphyromonas uenonis are frequently isolated from the human vagina and are linked to bacterial vaginosis and preterm labour. However, little is known about the pathogenesis mechanisms of these bacteria. The related oral opportunistic pathogen, Porphyromonas gingivalis, is comparatively well-studied and known to secrete numerous extracellular matrix-targeting proteases. Among these are the gingipain family of cysteine proteases that drive periodontal disease progression and hematogenic transmission to the placenta. Given their phylogenetic relatedness, we hypothesized that vaginal Porphyromonas species possess gingipain-like protease activity targeting host extracellular matrix in the female reproductive tract. In this study, we demonstrate that vaginal Porphyromonas species degrade type I collagen (cervix), type IV collagen (chorioamnion/placenta), and fibrinogen, but not through the activity of gingipain orthologs. Bioinformatic queries identified five candidate collagenases in each species, including serine, cysteine and metalloproteases, with signal peptides directing them to the extracellular environment. Inhibition assays revealed both species secrete metalloproteases that degrade collagen and casein, while P. asaccharolytica also secretes a metalloprotease that degrades fibrinogen. Phylogenetic analysis of the predicted collagen-degrading metalloprotease revealed an orthologous relationship with the P. gingivalis endopeptidase PepO. Cloning and expression of P. asaccharolytica PepO confirmed this protein's collagenase and caseinase activities, which have not previously been attributed to PepO homologs in other bacteria. Altogether, this description of the first known virulence factor in Porphyromonas species colonizing the human vagina sheds light on their potential to alter the structural integrity and homeostasis of reproductive tissues.

scholarly journals Functional Analysis of the Collagen Binding Proteins of Streptococcus parasanguinis FW213

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Yi-Ywan M. Chen ◽  
Pei-Hua Tsai ◽  
Zong-Sian Ye ◽  
Yu-Wen Huang ◽  
Hui-Ru Shieh ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Binding Proteins ◽  
Type I Collagen ◽  
Galleria Mellonella ◽  
Opportunistic Pathogen ◽  
Type I ◽  
Collagen Binding ◽  
Content Type ◽  
Extracellular Matrix Molecules ◽  
Streptococcus Parasanguinis

ABSTRACT Streptococcus parasanguinis is a dominant isolate of dental plaque and an opportunistic pathogen associated with subacute endocarditis. As the expression of collagen binding proteins (CBPs) could promote the establishment of S. parasanguinis in the host, the functions of three putative CBP-encoding loci, Spaf_0420, Spaf_1570, and Spaf_1573, were analyzed using isogenic mutant strains. It was revealed that S. parasanguinis FW213 bound effectively to fibronectin and type I collagen, but the strain’s affinity for laminin and type IV collagen was quite low. By using various deletion derivatives, it was found that these three loci mediated the binding of S. parasanguinis to multiple extracellular matrix molecules, with type I collagen as the common substrate. Derivative strains with a deletion in any of the three loci expressed reduced binding to trypsin-treated swine heart valves. The deletion of these loci also reduced the viable count of S. parasanguinis bacteria within macrophages, especially the loss of Spaf_0420, but only strains with deletions in Spaf_0420 and Spaf_1570 expressed reduced virulence in the Galleria mellonella larva model. The deletion of Spaf_1570 and Spaf_1573 affected mainly the structure, but not the overall mass, of biofilm cultures in a flow cell system. Thus, CBPs are likely to be more critical for the initial colonization of S. parasanguinis on host tissues during the development of endocarditis. IMPORTANCE Bacteria generally can utilize multiple adhesins to establish themselves in the host. We found that Streptococcus parasanguinis, a dominant oral commensal and an opportunistic pathogen for subacute endocarditis, possesses at least three collagen-binding proteins that enable S. parasanguinis to successfully colonize damaged heart tissues and escape innate immune clearance. The binding specificities of these three proteins for extracellular matrix molecules differ, although all three proteins participate in biofilm formation by S. parasanguinis. The “multiligand for multisubstrate” feature of these adhesins may explain the high adaptability of this microbe to different tissue sites.

scholarly journals The Dynamic Interaction between Extracellular Matrix Remodeling and Breast Tumor Progression

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1046
Author(s):  
Jorge Martinez ◽  
Patricio C. Smith
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Cell Metabolism ◽  
Breast Tumors ◽  
Extracellular Matrix Remodeling ◽  
Type I ◽  
Matrix Remodeling ◽  
Desmoplastic Reaction ◽  
The Impact

Desmoplastic tumors correspond to a unique tissue structure characterized by the abnormal deposition of extracellular matrix. Breast tumors are a typical example of this type of lesion, a property that allows its palpation and early detection. Fibrillar type I collagen is a major component of tumor desmoplasia and its accumulation is causally linked to tumor cell survival and metastasis. For many years, the desmoplastic phenomenon was considered to be a reaction and response of the host tissue against tumor cells and, accordingly, designated as “desmoplastic reaction”. This notion has been challenged in the last decades when desmoplastic tissue was detected in breast tissue in the absence of tumor. This finding suggests that desmoplasia is a preexisting condition that stimulates the development of a malignant phenotype. With this perspective, in the present review, we analyze the role of extracellular matrix remodeling in the development of the desmoplastic response. Importantly, during the discussion, we also analyze the impact of obesity and cell metabolism as critical drivers of tissue remodeling during the development of desmoplasia. New knowledge derived from the dynamic remodeling of the extracellular matrix may lead to novel targets of interest for early diagnosis or therapy in the context of breast tumors.

Regulation of extracellular matrix production by chemically synthesized subfragments of type I collagen carboxy propeptide

Biochemistry ◽  
1991 ◽  
Vol 30 (29) ◽  
pp. 7097-7104 ◽  
Author(s):  
Kou Katayama ◽  
Jerome M. Seyer ◽  
Rajendra Raghow ◽  
Andrew H. Kang
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Type I ◽  
Extracellular Matrix Production ◽  
Matrix Production

Hypoxia and reoxygenation stimulate biphasic changes in endothelial monolayer permeability

1995 ◽  
Vol 269 (1) ◽  
pp. L52-L58 ◽  
Author(s):  
C. A. Partridge
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Stress Fibers ◽  
Type I ◽  
Endothelial Monolayer ◽  
Hypoxic Conditions ◽  
Endothelial Monolayers ◽  
Monolayer Permeability ◽  
Hypoxic Incubation ◽  
Intercellular Gaps

Incubation of bovine pulmonary microvascular endothelial (BPMVE) cells in low O2 content (95% N2-5% CO2) for 4 h increased monolayer permeability to dextran almost twofold and also increased the incidence of intercellular gaps and intracellular actin stress fibers. Hypoxic incubation decreased the extracellular matrix contents of fibronectin and vitronectin, proteins that serve as anchorage points for the endothelial cells. This state was reversed after 24 h of hypoxic incubation, and the BPMVE monolayer permeability to dextran was less than that of normoxic controls. The monolayer had fewer intercellular gaps and stress fibers, and the extracellular matrix contained increased amounts of fibronectin, vitronectin, and type I collagen. These alterations stimulated by 24 h of hypoxic incubation were resolved within 4 h of reoxygenation in room air supplemented with 5% CO2. These studies indicate that incubation of endothelial monolayers in hypoxic conditions first increases and then decreases monolayer permeability, through increased and decreased formation of intercellular gaps.

scholarly journals Binding of Brucella protein, Bp26, to select extracellular matrix molecules

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Yasmin ElTahir ◽  
Amna Al-Araimi ◽  
Remya R. Nair ◽  
Kaija J. Autio ◽  
Hongmin Tu ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Host Cells ◽  
Mouse Serum ◽  
Enzyme Linked Immunosorbent Assay ◽  
Target Cells ◽  
Type I ◽  
Dependent Manner ◽  
Biolayer Interferometry

Abstract Background Brucella is a facultative intracellular pathogen responsible for zoonotic disease brucellosis. Little is known about the molecular basis of Brucella adherence to host cells. In the present study, the possible role of Bp26 protein as an adhesin was explored. The ability of Brucella protein Bp26 to bind to extracellular matrix (ECM) proteins was determined by enzyme-linked immunosorbent assay (ELISA) and biolayer interferometry (BLI). Results ELISA experiments showed that Bp26 bound in a dose-dependent manner to both immobilized type I collagen and vitronectin. Bp26 bound weakly to soluble fibronectin but did not bind to immobilized fibronectin. No binding to laminin was detected. Biolayer interferometry showed high binding affinity of Bp26 to immobilized type I collagen and no binding to fibronectin or laminin. Mapping of Bp26 antigenic epitopes by biotinylated overlapping peptides spanning the entire sequence of Bp26 using anti Bp26 mouse serum led to the identification of five linear epitopes. Collagen and vitronectin bound to peptides from several regions of Bp26, with many of the binding sites for the ligands overlapping. The strongest binding for anti-Bp26 mouse serum, collagen and vitronectin was to the peptides at the C-terminus of Bp26. Fibronectin did not bind to any of the peptides, although it bound to the whole Bp26 protein. Conclusions Our results highlight the possible role of Bp26 protein in the adhesion process of Brucella to host cells through ECM components. This study revealed that Bp26 binds to both immobilized and soluble type I collagen and vitronectin. It also binds to soluble but not immobilized fibronectin. However, Bp26 does not bind to laminin. These are novel findings that offer insight into understanding the interplay between Brucella and host target cells, which may aid in future identification of a new target for diagnosis and/or vaccine development and prevention of brucellosis.

Mechanical Signaling and Extracellular Matrix in Uterine Fibroids

2017 ◽  
Vol 35 (06) ◽  
pp. 487-493 ◽  
Author(s):  
Saima Rafique ◽  
James Segars ◽  
Phyllis Leppert
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Reproductive Tract ◽  
Critical Role ◽  
Uterine Fibroids ◽  
Female Reproductive Tract ◽  
Benign Tumors ◽  
Mechanical Signaling ◽  
Abnormal Cells ◽  
Fibroid Growth

AbstractFibroids (uterine leiomyomas) are the most common benign tumors of the female reproductive tract. Steroid hormones, growth factors, and cytokines have long been implicated in fibroid growth; however, research suggests that changes in the extracellular matrix and mechanical signaling play a critical role in fibroid growth and differentiation. Studies have shown that growth of fibroids is related to the change in the volume and composition of extracellular matrix with increased deposition of abnormal collagen, glycoproteins, laminins, fibronectins, and an increased osmotic stress. These changes generate mechanical stress which is converted to chemical signals in the cells through mechanotransduction and eventually affects gene expression and protein synthesis. Current studies also suggest that mechanical signaling in fibroid cells is abnormal as evidenced by decreased apoptosis of abnormal cells and deposition of a stiff extracellular matrix promoting fibrosis. Understanding and defining these mechanisms could help design new therapies for the treatment of fibroids.

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