scholarly journals The role of dsbA in colonization of the wheat rhizosphere by Pseudomonas fluorescens Q8r1-96

Microbiology ◽  
2006 ◽  
Vol 152 (3) ◽  
pp. 863-872 ◽  
Author(s):  
Olga V. Mavrodi ◽  
Dmitri V. Mavrodi ◽  
Amanda A. Park ◽  
David M. Weller ◽  
Linda S. Thomashow
Keyword(s):  
Cell Surface ◽  
Pseudomonas Fluorescens ◽  
Parental Strain ◽  
Critical Role ◽  
Surface Structures ◽  
Gaeumannomyces Graminis ◽  
Natural Soil ◽  
Cell Surface Structures

Certain well-conserved genes in fluorescent Pseudomonas spp. are involved in pathogenic interactions between the bacteria and evolutionarily diverse hosts including plants, insects and vertebrate animals. One such gene, dsbA, encodes a periplasmic disulfide-bond-forming enzyme implicated in the biogenesis of exported proteins and cell surface structures. This study focused on the role of dsbA in Pseudomonas fluorescens Q8r1-96, a biological control strain that produces the antibiotic 2,4-diacetylphloroglucinol (2,4-DAPG) and is known for its exceptional ability to colonize the roots of wheat and pea. The deduced DsbA protein from Q8r1-96 is similar to other predicted thiol : disulfide interchange proteins and contains a conserved DsbA catalytic site, a pattern associated with the thioredoxin family active site, and a signal peptide and cleavage site. A dsbA mutant of Q8r1-96 exhibited decreased motility and fluorescence, and altered colony morphology; however, it produced more 2,4-DAPG and total phloroglucinol-related compounds and was more inhibitory in vitro to the fungal root pathogen Gaeumannomyces graminis var. tritici than was the parental strain. When introduced separately into a natural soil, Q8r1-96 and the dsbA mutant did not differ in their ability to colonize the rhizosphere of wheat in greenhouse experiments lasting 12 weeks. However, when the two strains were co-inoculated, the parental strain consistently out-competed the dsbA mutant. It was concluded that dsbA does not contribute to the exceptional rhizosphere competence of Q8r1-96, although the dsbA mutation reduces competitiveness when the mutant competes with the parental strain in the same niche in the rhizosphere. The results also suggest that exoenzymes and multimeric cell surface structures are unlikely to have a critical role in root colonization by this strain.

scholarly journals Phage Resistance in Multidrug-Resistant Klebsiella pneumoniae ST258 Evolves via Diverse Mutations That Culminate in Impaired Adsorption

mBio ◽  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Shayla Hesse ◽  
Manoj Rajaure ◽  
Erin Wall ◽  
Joy Johnson ◽  
Valery Bliskovsky ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Cell Surface ◽  
Phage Therapy ◽  
Surface Structures ◽  
Phage Resistance ◽  
Cell Surface Structures ◽  
Phage Cocktail ◽  
Resistant Mutants

ABSTRACT The evolution of phage resistance poses an inevitable threat to the efficacy of phage therapy. The strategic selection of phage combinations that impose high genetic barriers to resistance and/or high compensatory fitness costs may mitigate this threat. However, for such a strategy to be effective, the evolution of phage resistance must be sufficiently constrained to be consistent. In this study, we isolated lytic phages capable of infecting a modified Klebsiella pneumoniae clinical isolate and characterized a total of 57 phage-resistant mutants that evolved from their prolonged coculture in vitro. Single- and double-phage-resistant mutants were isolated from independently evolved replicate cocultures grown in broth or on plates. Among resistant isolates evolved against the same phage under the same conditions, mutations conferring resistance occurred in different genes, yet in each case, the putative functions of these genes clustered around the synthesis or assembly of specific cell surface structures. All resistant mutants demonstrated impaired phage adsorption, providing a strong indication that these cell surface structures functioned as phage receptors. Combinations of phages targeting different host receptors reduced the incidence of resistance, while, conversely, one three-phage cocktail containing two phages targeting the same receptor increased the incidence of resistance (relative to its two-phage, nonredundant receptor-targeting counterpart). Together, these data suggest that laboratory characterization of phage-resistant mutants is a useful tool to help optimize therapeutic phage selection and cocktail design. IMPORTANCE The therapeutic use of bacteriophage (phage) is garnering renewed interest in the setting of difficult-to-treat infections. Phage resistance is one major limitation of phage therapy; therefore, developing effective strategies to avert or lessen its impact is critical. Characterization of in vitro phage resistance may be an important first step in evaluating the relative likelihood with which phage-resistant populations emerge, the most likely phenotypes of resistant mutants, and the effect of certain phage cocktail combinations in increasing or decreasing the genetic barrier to resistance. If this information confers predictive power in vivo, then routine studies of phage-resistant mutants and their in vitro evolution should be a valuable means for improving the safety and efficacy of phage therapy in humans.

scholarly journals CRITICAL ROLE OF DETERMINANT PRESENTATION IN THE INDUCTION OF SPECIFIC RESPONSES IN IMMUNO-COMPETENT LYMPHOCYTES

1973 ◽  
Vol 137 (4) ◽  
pp. 967-990 ◽  
Author(s):  
David H. Katz ◽  
Emil R. Unanue
Keyword(s):  
T Cells ◽  
B Cells ◽  
T Lymphocytes ◽  
Cell Surface ◽  
Critical Role ◽  
Antibody Responses ◽  
Soluble Antigen ◽  
Protein Conjugates

A detailed analysis of the role of determinant presentation in the process of triggering immunocompetent lymphocytes has been made utilizing cell-bound hapten-carrier conjugates to elicit secondary antihapten antibody responses, primarily in vitro. The results of these experiments demonstrate that: (a) hapten-protein conjugates will attach to the surface membranes of macrophages directly, in the absence of specific antibodies, in a highly immunogenic form; (b) such macrophage-bound conjugates serve as remarkedly efficient stimuli to trigger both thymus-derived (T) and bone marrow-derived (B) cells in a specific manner, lowering the optimal threshold antigen dose (in molar terms) by several logs as compared with soluble antigen; (c) the macrophage is not unique in this regard, since fibroblasts are essentially comparable in the capacity to present antigen in highly immunogenic form; (d) cell surface-bound antigen clearly favors secondary in vitro responses of the IgG as compared with the IgM antibody class; (e) in terms of triggering B or T cells, antigen bound to macrophages in the form of immune complexes does not appear to possess any appreciable advantage over equimolar quantities of directly attached antigen; (f) the increased immunogenicity of cell-bound antigen appears to reflect certain crucial, and undefined, features of cell surface membranes and not merely the stabilization of determinants on a relatively immobile surface; and (g) although the efficiency of lymphocyte triggering is markedly enhanced by cell-bound antigen, the presence of macrophages is apparently not an absolute requirement for eliciting secondary in vitro antibody responses to soluble hapten-protein conjugates. The relevance of these observations to the nature of the signal induced upon antigen interaction by specific lymphocytes and the sequential cellular events involved in the regulatory influence of activated T cells on B cell responses to antigen is discussed. We postulate that T lymphocytes are best triggered by cell-bound antigen and that after this step the activated T lymphocytes regulate the triggering of B cells with antigen.

scholarly journals Role of Cell Surface Structures in Biofilm Formation by <i>Escherichia coli</i>

2015 ◽  
Vol 06 (12) ◽  
pp. 1160-1165 ◽  
Author(s):  
Hafida Zahir ◽  
Hamadi Fatima ◽  
Lekchiri Souad ◽  
Mliji El Mostafa ◽  
Ellouali Mostafa ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Surface ◽  
Biofilm Formation ◽  
Surface Structures ◽  
Cell Surface Structures

scholarly journals NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2999
Author(s):  
Deborah Reynaud ◽  
Roland Abi Nahed ◽  
Nicolas Lemaitre ◽  
Pierre-Adrien Bolze ◽  
Wael Traboulsi ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Cells ◽  
Major Gene ◽  
Critical Role ◽  
Orthotopic Model ◽  
Independent Manner ◽  
Maternal Immune Response ◽  
The Impact

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.

scholarly journals The role of the PZP domain of AF10 in acute leukemia driven by AF10 translocations

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Brianna J. Klein ◽  
Anagha Deshpande ◽  
Khan L. Cox ◽  
Fan Xuan ◽  
Mohamad Zandian ◽  
...  
Keyword(s):  
Critical Role ◽  
Cellular Transformation ◽  
Acute Leukemias ◽  
Hematopoietic Stem ◽  
Nucleosome Core ◽  
Stem And Progenitor Cells ◽  
Transforming Activity

AbstractChromosomal translocations of the AF10 (or MLLT10) gene are frequently found in acute leukemias. Here, we show that the PZP domain of AF10 (AF10PZP), which is consistently impaired or deleted in leukemogenic AF10 translocations, plays a critical role in blocking malignant transformation. Incorporation of functional AF10PZP into the leukemogenic CALM-AF10 fusion prevents the transforming activity of the fusion in bone marrow-derived hematopoietic stem and progenitor cells in vitro and in vivo and abrogates CALM-AF10-mediated leukemogenesis in vivo. Crystallographic, biochemical and mutagenesis studies reveal that AF10PZP binds to the nucleosome core particle through multivalent contacts with the histone H3 tail and DNA and associates with chromatin in cells, colocalizing with active methylation marks and discriminating against the repressive H3K27me3 mark. AF10PZP promotes nuclear localization of CALM-AF10 and is required for association with chromatin. Our data indicate that the disruption of AF10PZP function in the CALM-AF10 fusion directly leads to transformation, whereas the inclusion of AF10PZP downregulates Hoxa genes and reverses cellular transformation. Our findings highlight the molecular mechanism by which AF10 targets chromatin and suggest a model for the AF10PZP-dependent CALM-AF10-mediated leukemogenesis.

scholarly journals The Inflammatory Role of Pro-Resolving Mediators in Endometriosis: An Integrative Review

2021 ◽  
Vol 22 (9) ◽  
pp. 4370
Author(s):  
Cássia de Fáveri ◽  
Paula M. Poeta Fermino ◽  
Anna P. Piovezan ◽  
Lia K. Volpato
Keyword(s):  
Intracellular Signaling ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Integrative Review ◽  
Inflammatory Factors ◽  
Resolvin D1 ◽  
Endogenous Factors

The pathogenesis of endometriosis is still controversial, although it is known that the inflammatory immune response plays a critical role in this process. The resolution of inflammation is an active process where the activation of endogenous factors allows the host tissue to maintain homeostasis. The mechanisms by which pro-resolving mediators (PRM) act in endometriosis are still little explored. Thus, this integrative review aims to synthesize the available content regarding the role of PRM in endometriosis. Experimental and in vitro studies with Lipoxin A4 demonstrate a potential inhibitory effect on endometrial lesions’ progression, attenuating pro-inflammatory and angiogenic signals, inhibiting proliferative and invasive action suppressing intracellular signaling induced by cytokines and estradiol, mainly through the FPR2/ALX. Investigations with Resolvin D1 demonstrated the inhibition of endometrial lesions and decreased pro-inflammatory factors. Annexin A1 is expressed in the endometrium and is specifically present in women with endometriosis, although the available studies are still inconsistent. Thus, we believe there is a gap in knowledge regarding the PRM pathways in patients with endometriosis. It is important to note that these substances’ therapeutic potential is evident since the immune and abnormal inflammatory responses play an essential role in endometriosis development and progression.

scholarly journals Role of Cathepsin S in Periodontal Inflammation and Infection

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
S. Memmert ◽  
A. Damanaki ◽  
A. V. B. Nogueira ◽  
S. Eick ◽  
M. Nokhbehsaim ◽  
...  
Keyword(s):  
Periodontal Diseases ◽  
Interleukin 1 ◽  
Critical Role ◽  
Gingival Tissue ◽  
Cathepsin S ◽  
Protein Levels ◽  
Periodontal Inflammation

Cathepsin S is a cysteine protease and regulator of autophagy with possible involvement in periodontitis. The objective of this study was to investigate whether cathepsin S is involved in the pathogenesis of periodontal diseases. Human periodontal fibroblasts were cultured under inflammatory and infectious conditions elicited by interleukin-1β and Fusobacterium nucleatum, respectively. An array-based approach was used to analyze differential expression of autophagy-associated genes. Cathepsin S was upregulated most strongly and thus further studied in vitro at gene and protein levels. In vivo, gingival tissue biopsies from rats with ligature-induced periodontitis and from periodontitis patients were also analyzed at transcriptional and protein levels. Multiple gene expression changes due to interleukin-1β and F. nucleatum were observed in vitro. Both stimulants caused a significant cathepsin S upregulation. A significantly elevated cathepsin S expression in gingival biopsies from rats with experimental periodontitis was found in vivo, as compared to that from control. Gingival biopsies from periodontitis patients showed a significantly higher cathepsin S expression than those from healthy gingiva. Our findings provide original evidence that cathepsin S is increased in periodontal cells and tissues under inflammatory and infectious conditions, suggesting a critical role of this autophagy-associated molecule in the pathogenesis of periodontitis.

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