scholarly journals Complement and Fc Function Are Required for Optimal Antibody Prophylaxis against Pneumocystis carinii Pneumonia

2006 ◽  
Vol 74 (1) ◽  
pp. 390-393 ◽  
Author(s):  
Jesse Wells ◽  
Constantine G. Haidaris ◽  
Terry W. Wright ◽  
Francis Gigliotti
Keyword(s):  
Monoclonal Antibody ◽  
Fungal Pathogen ◽  
Complement Fixation ◽  
Pneumocystis Carinii ◽  
Immunocompromised Host ◽  
Scid Mice ◽  
Maximum Effect ◽  
Opportunistic Fungal Pathogen ◽  
Optimal Effect

ABSTRACT Pneumocystis carinii is an opportunistic fungal pathogen that causes P. carinii pneumonia (PCP) in the immunocompromised host. We investigated the role of antibody Fc-mediated function in passive prophylaxis against the development of PCP in SCID mice. By comparison of anti-mouse P. carinii immunoglobulin G1 monoclonal antibody (MAb) 4F11(G1) and its F(ab′)2 derivative in an intranasal immunoprophylaxis model, we determined that Fc-mediated function is required for maximum effect of this antibody. Comparison of efficacy of antibody prophylaxis in SCID mice depleted of complement to that in nondepleted mice demonstrated that complement fixation by MAb 4F11(G1) is also necessary for optimal effect of passively administered antibody, although residual protection was observed in complement-depleted SCID mice. The necessity of complement for optimal PCP prophylaxis by MAb 4F11(G1) suggests that complement may play a role in antibody-mediated protection against development of PCP.

scholarly journals Pneumocystis Melanins Confer Enhanced Organism Viability

2006 ◽  
Vol 5 (6) ◽  
pp. 916-923 ◽  
Author(s):  
Crystal R. Icenhour ◽  
Theodore J. Kottom ◽  
Andrew H. Limper
Keyword(s):  
Fungal Pathogen ◽  
Pneumocystis Carinii ◽  
Environmental Stressors ◽  
Resonance Spectroscopy ◽  
Reverse Transcription Pcr ◽  
Spin Resonance ◽  
Opportunistic Fungal Pathogen ◽  
Adverse Environmental Conditions ◽  
Previous Identification

ABSTRACT Pneumocystis continues to represent an important opportunistic fungal pathogen of those with compromised immunity. Thus, it is crucial to identify factors that affect its viability and pathogenicity. We previously reported the first identification of melanins in Pneumocystis. In the present study, we sought to further characterize these components and define the function for these melanins. Melanins extracted from Pneumocystis and melanized Pneumocystis cells were analyzed by electron spin resonance spectroscopy, revealing spectra consistent with melanins from other fungi. Immunofluorescence assays using anti-melanin monoclonal antibodies showed that melanins are widely present across Pneumocystis host species, including mouse-, ferret-, and human-derived Pneumocystis organisms, as well as Pneumocystis carinii derived from rat. Using immunoelectron microscopy, melanins were found to localize to the cell wall and cytoplasm of P. carinii cysts, as well as to intracystic bodies within mature cysts. Next, the role of melanins on the maintenance of Pneumocystis viability was determined by using quantitative reverse transcription-PCR measurement of the heat shock protein mRNA under adverse environmental conditions. Using a new method to promote the melanization of Pneumocystis, we observed that strongly melanized Pneumocystis retained viability to a greater degree when exposed to UV irradiation or desiccation compared to less-pigmented organisms. These studies support our previous identification of Pneumocystis melanins across the genus, further characterize these Pneumocystis components, and demonstrate that melanins protect Pneumocystis from environmental stressors.

scholarly journals Epitope Mapping of a Protective Monoclonal Antibody against Pneumocystis carinii with Shared Reactivity to Streptococcus pneumoniae Surface Antigen PspA

2004 ◽  
Vol 72 (3) ◽  
pp. 1548-1556 ◽  
Author(s):  
Jesse Wells ◽  
Francis Gigliotti ◽  
Patricia J. Simpson-Haidaris ◽  
Constantine G. Haidaris
Keyword(s):  
Monoclonal Antibody ◽  
Streptococcus Pneumoniae ◽  
Surface Antigen ◽  
Pneumocystis Carinii ◽  
Immunocompromised Host ◽  
Immunofluorescence Assay ◽  
Recombinant Polypeptide ◽  
Intact Mouse ◽  
Bacterial Surface ◽  
Opportunistic Fungal Pathogen

ABSTRACT Pneumocystis carinii is an opportunistic fungal pathogen that causes pneumonia in the immunocompromised host. A protective monoclonal antibody (MAb) termed 4F11 generated against mouse-derived P. carinii was shown by indirect immunofluorescence assay (IFA) to bind surface antigens of P. carinii derived from multiple host species, including humans. We have identified multiple epitopes recognized by MAb 4F11 in two recombinant mouse P. carinii antigens. The epitopes mapped have similar proline content and positive charge distribution. The consensus 8-mer epitope recognized by MAb 4F11 is K/RPA/RPK/QPA/TP. Immune sera raised against intact mouse P. carinii recognized native antigens affinity purified with MAb 4F11 and a recombinant antigen reactive with MAb 4F11. Database searches for short, nearly exact matches to the mapped MAb 4F11 epitopes identified a bacterial surface antigen, Streptococcus pneumoniae PspA, with a similar proline-rich region. In an IFA, MAb 4F11 detected antigens on the S. pneumoniae surface, and Western blotting identified a protein in S. pneumoniae lysates consistent with the Mr of PspA. A fragment of the S. pneumoniae PspA gene was cloned and sequenced, and the deduced amino acid sequence contained a region with strong similarity to the MAb 4F11 epitopes identified in P. carinii. The PspA recombinant polypeptide was recognized by MAb 4F11 in a Western blot. The ability of MAb 4F11 to recognize similar proline-rich epitopes may explain its ability to recognize P. carinii derived from multiple hosts and will permit testing of the epitopes recognized by this antibody in immunization against P. carinii.

scholarly journals Multifactorial Role of Mitochondria in Echinocandin Tolerance Revealed by Transcriptome Analysis of Drug-Tolerant Cells

mBio ◽  
2021 ◽  
Author(s):  
Rocio Garcia-Rubio ◽  
Cristina Jimenez-Ortigosa ◽  
Lucius DeGregorio ◽  
Christopher Quinteros ◽  
Erika Shor ◽  
...  
Keyword(s):  
Fungal Pathogen ◽  
Candida Glabrata ◽  
Clinical Failure ◽  
First Line ◽  
Content Type ◽  
First Line Therapy ◽  
Line Therapy ◽  
Resistant Strains ◽  
Opportunistic Fungal Pathogen

Echinocandin drugs are a first-line therapy to treat invasive candidiasis, which is a major source of morbidity and mortality worldwide. The opportunistic fungal pathogen Candida glabrata is a prominent bloodstream fungal pathogen, and it is notable for rapidly developing echinocandin-resistant strains associated with clinical failure.

scholarly journals Characterization of the Pneumocystis carinii Histone Acetyltransferase Chaperone Proteins PcAsf1 and PcVps75

2013 ◽  
Vol 81 (6) ◽  
pp. 2268-2275 ◽  
Author(s):  
Jakrapun Pupaibool ◽  
Theodore J. Kottom ◽  
Kelly Bouchonville ◽  
Andrew H. Limper
Keyword(s):  
Dna Replication ◽  
Cell Cycle Progression ◽  
Pneumocystis Carinii ◽  
Histone H3 ◽  
Content Type ◽  
Dna Replication And Repair ◽  
Opportunistic Fungal Pathogen ◽  
Vacuolar Protein

ABSTRACTRtt109 is a lysine acetyltransferase that acetylates histone H3 at lysine 56 (H3K56) in fungi. This acetylation event is important for proper DNA replication and repair to occur. Efficient Rtt109 acetyltransferase activity also requires a histone chaperone, vacuolar protein sorting 75 (Vps75), as well as the major chaperone of the H3-H4 dimer, anti-silencing factor 1 (Asf1). Little is known about the role of these proteins in the opportunistic fungal pathogenPneumocystis carinii. To investigate the functions of Asf1 and Vps75 inPneumocystis carinii, we cloned and characterized both of these genes. Here, we demonstrate that both genes,P. carinii asf1(Pcasf1) andPcvps75, function in a fashion analogous to theirSaccharomyces cerevisiaecounterparts. We demonstrate that bothP. cariniiAsf1 (PcAsf1) and PcVps75 can bind histones. Furthermore, whenPcasf1is expressed heterologously inS. cerevisiae asf1Δ cells, PcAsf1 can restore full H3 lysine acetylation. We further demonstrated that thePcasf1cDNA expressed inasf1ΔS. cerevisiaecells can restore growth to wild-type levels in the presence of genotoxic agents that block DNA replication. Lastly, we observed that purified PcAsf1 and PcVps75 proteins enhance the ability of PcRtt109 to acetylate histone H3-H4 tetramers. Together, our results indicate that the functions of the Rtt109-Asf1-Vps75 complex in the acetylation of histone H3 lysine 56 and in DNA damage response are present inP. cariniiDNA and cell cycle progression.

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 The Role of Secretory Pathways in Candida albicans Pathogenesis

2020 ◽  
Vol 6 (1) ◽  
pp. 26 ◽  
Author(s):  
Christiane Rollenhagen ◽  
Sahil Mamtani ◽  
Dakota Ma ◽  
Reva Dixit ◽  
Susan Eszterhas ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Membrane Trafficking ◽  
Fungal Pathogen ◽  
Biofilm Formation ◽  
Secretory Pathways ◽  
Associated Proteins ◽  
Normal Human ◽  
Opportunistic Fungal Pathogen ◽  
Hyphal Formation

Candida albicans is a fungus that is a commensal organism and a member of the normal human microbiota. It has the ability to transition into an opportunistic invasive pathogen. Attributes that support pathogenesis include secretion of virulence-associated proteins, hyphal formation, and biofilm formation. These processes are supported by secretion, as defined in the broad context of membrane trafficking. In this review, we examine the role of secretory pathways in Candida virulence, with a focus on the model opportunistic fungal pathogen, Candida albicans.

Role of Candida albicans Aft2p transcription factor in ferric reductase activity, morphogenesis and virulence

Microbiology ◽  
2010 ◽  
Vol 156 (10) ◽  
pp. 2912-2919 ◽  
Author(s):  
Yong Liang ◽  
Dongsheng Wei ◽  
Hui Wang ◽  
Ning Xu ◽  
Biao Zhang ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Functional Analysis ◽  
Candida Albicans ◽  
Fungal Pathogen ◽  
Reductase Activity ◽  
Growth Defect ◽  
Ferric Reductase ◽  
Opportunistic Fungal Pathogen ◽  
Affect Cell Growth

The ability of Candida albicans to act as an opportunistic fungal pathogen is linked to its ability to switch among different morphological forms. This conversion is an important feature of C. albicans and is correlated with its pathogenesis. Many conserved positive and negative transcription factors regulate morphogenetic transition of C. albicans. Here, we show the results of functional analysis of CaAFT2, which is an orthologue of the Saccharomyces cerevisiae AFT2 gene. We have cloned CaAFT2 which has an ability to complement the S. cerevisiae aft1Δ mutant strain growth defect. Interestingly, although disruption of the AFT2 gene did not affect cell growth in solid and liquid iron-limited conditions, the cell surface ferric reductase activity was significantly decreased. Importantly, deletion of AFT2 in C. albicans led to growth of a smooth colony with no peripheral hyphae. Moreover, virulence of an aft2Δ/aft2Δ mutant was markedly attenuated in a mouse model. Our results suggest that CaAft2p represents a novel activator and that it functions in ferric reductase activity, morphogenesis and virulence in C. albicans.

Epidemiology and antimicrobial resistance of Acinetobacter

2018 ◽  
Vol 2 (4) ◽  
pp. 46-59
Author(s):  
A.G. Salmanov ◽  
O.M. Verner ◽  
L.F. Slepova
Keyword(s):  
Antibiotic Resistance ◽  
Laboratory Testing ◽  
Immunocompromised Host ◽  
Clinical Problem ◽  
Healthcare Associated Infections ◽  
Opportunistic Bacteria ◽  
Acinetobacter Spp ◽  
Healthcare Associated ◽  
Major Clinical Problem

Species of the Acinetobacter represent opportunistic bacteria with a growing clinical significance for Healthcare-associated infections (HAIs). In this literature review, we focus on the current role of Acinetobacter in infectious pathology and describe taxonomy, pathogenicity, and antibiotic resistance of these bacteria. Pathogenesis and regulation of virulence factors in Acinetobacter spp. are described in detail. The majority of acinetobacterial infections are associated with A. baumannii and occur predominantly in an immunocompromised host. Usually, acinetobacterial  infections  are characterized by local purulent inflammation; in severe cases, meningitis and sepsis may develop. Antibiotic resistance of Acinetobacter is a major clinical problem; therefore we give special attention to laboratory testing of resistance to antibiotics as well as identification of Acinetobacter.

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