Medical Microbiology Commons^™

Functional And Transcriptomic Changes In Synergy Of Endotoxin And (1->3)-Β-D-Glucan In Bone Marrow Derived Macrophage From Fc Gamma Receptor Iib Deficient Mice, Jiraphorn Issara-Amphorn

Chulalongkorn University Theses and Dissertations (Chula ETD)

Systemic lupus erythematosus (SLE) is an autoimmune disease with a diverse array of clinical symptoms. There are many factors including environmental factors may trigger disease progression. In this study, we investigated the influence of spontaneous gut leakage upon polymicrobial sepsis in Fc gamma receptor IIb deficient (FcgRIIb-/-) mice aged 8 and 40 weeks, as representing asymptomatic and symptomatic lupus, respectively. The spontaneous gut leakage as determined by i) the level of serum FITC-dextran, ii) increased serum endotoxin (LPS), and iii) increased serum (1->3)-b-D-glucan (BG), were demonstrated in symptomatic FcgRIIb-/- mice, but not in asymptomatic group. Moreover, spontaneous gut leakage …

The Effect Of A Trehalase Inhibitor, Validamycin A, On The Growth Of Aspergillus Flavus, Napasawan Plabutong

Chulalongkorn University Theses and Dissertations (Chula ETD)

Aspergillus flavus is a fungus found in the environment causing keratitis, cutaneous infections, sinusitis, invasive pulmonary aspergillosis in humans. Although this fungus can be treated with antifungal agents, these main antifungal agents have many side effects. Trehalase is an enzyme for digesting trehalose into two glucose subunits and is essential for virulence in many fungi. A trehalase inhibitor, called validamycin A, has been used effectively against a rice fungal pathogen, Rhizoctonia solani. In this study, we observed that validamycin A increased trehalose levels significantly in A. flavus spores and delayed the germination of those spores. In addition, to further investigate …

Development Of Polymerase Chain Reaction Enzyme Linked Immunosorbent Assay For Detection Of Human Papillomavirus 16 L1 Gene Methylation, Sasiprapa Liewchalermwong

Chulalongkorn University Theses and Dissertations (Chula ETD)

It has been well known that cervical cancer is caused by persistent infections with the high risk human papillomavirus (HR-HPV) especially HPV16 and 18. However, a minority of HR-HPV infected women developed cancer, therefore, triage test is necessary to particularly select some HR-HPV infected women who are at higher risk to progress to cervical cancer quickly for colposcopy examination. Since HPV16 L1 gene hypermethylation has been reported to be correlated well with high grade cervical lesions and cancer, the present study aims to develop PCR-ELISA for detection of HPV16 L1 gene methylation. Cervical cells were collected from women who referred …

The Role Of Chromatin Structure In Cellular Responses To Bacterial Cytolethal Distending Toxin In Saccharomyces Cerevisiae Model, Siriyod Denmongkholchai

Chulalongkorn University Theses and Dissertations (Chula ETD)

Cytolethal distending toxin subunit B (CdtB) is a DNase I-like bacterial genotoxin that causes DNA damage leading to cell cycle arrest and cell death. Previous reports demonstrated that CdtB has low level of DNase activity in vitro. Besides, a mutation at histone H2B phosphorylation site required for chromatin condensation during apoptosis (S10A) conferred partial resistance to CdtB in Saccharomyces cerevisiae model. Therefore, we hypothesized that chromatin structure may affect CdtB function. In this study, we identified chromatin regulators required for CdtB cytotoxicity in yeast. We found that deletions of certain components of SWR-complex (SWR1, SWC2, SWC5, SWC6, and ARP6), INO80-complex …

Characterization Of Mait Tcr Repertoire Of Gastrointestinal Tract And Peripheral Blood Mait Cells, Thidarat Kongkaew

Chulalongkorn University Theses and Dissertations (Chula ETD)

Mucosal-associated invariant T (MAIT) cells are an innate-like T cell that rapidly respond to infection. MAIT cells are αβ T cells that possess a Vα7.2 (TRAV1-2) TCR with mostly pairing to TRAJ33, TRAJ20 or TRAJ12 and predominantly TRBV20-1, TRBV6-1 and TRBV6-4. MAIT T cell receptors (TCR) repertoire have been previously studied in peripheral blood. However, data on MAIT TCR repertoire in gastrointestinal tract are lacking. We studied 2 individuals who are underwent esophagogastroduodenoscopy (EGD) and colonoscopy. Blood and biopsies were obtained. PBMCs were isolated from blood and LPLs were isolated from biopsies. Due to the low number of MAIT cells …

Effects Of Non-Albicans Candida Species On Biofilm Formation And Acidogenicity Of Dual-Species Biofilms And On Cariogenic Virulence Gene Expression Of Streptococcus Mutans, Wirunphat Sansanoa

Chulalongkorn University Theses and Dissertations (Chula ETD)

Early childhood caries is a common oral disease found in children which could affect their general health. Streptococcus mutans is an important cariogenic pathogen since it possesses cariogenic properties, which are acid production, acid tolerance and biofilm formation. Recent studies showed that Candida albicans, which is frequently found together with S. mutans in plaques of children with dental caries, enhances cariogenicity. At the same time, increasing prevalence of non-albicans Candida species (NACs) in children and immune-compromised patients has been reported. Therefore, this study aims to investigate the effects of NACs when co-cultured with S. mutans on cariogenic properties and virulence …

Inhibition Of Cancer Stem Cells By Glycosaminoglycan Mimetics, Connor P. O'Hara

Theses and Dissertations

Connor O’Hara July 29, 2019

Inhibition of Cancer Stem Cells by Glycosaminoglycan Mimetics

In the United States cancer is the second leading cause of death, with colorectal cancer (CRC) being the third deadliest cancer and expected to cause over 51,000 fatalities in 2019 alone.¹ The current standard of care for CRC depends largely on the staging, location, and presence of metastasis.² As the tumor grows and invades nearby lymph tissue and blood vessels, CRC has the opportunity to invade not only nearby tissue but also metastasize into the liver and lung (most commonly).³ The 5-year survival rate …

Effects Of Non-Albicans Candida Species On Biofilm Formation And Acidogenicity Of Dual-Species Biofilms And On Cariogenic Virulence Gene Expression Of Streptococcus Mutans, Wirunphat Sansanoa

Chulalongkorn University Theses and Dissertations (Chula ETD)

Early childhood caries is a common oral disease found in children which could affect their general health. Streptococcus mutans is an important cariogenic pathogen since it possesses cariogenic properties, which are acid production, acid tolerance and biofilm formation. Recent studies showed that Candida albicans, which is frequently found together with S. mutans in plaques of children with dental caries, enhances cariogenicity. At the same time, increasing prevalence of non-albicans Candida species (NACs) in children and immune-compromised patients has been reported. Therefore, this study aims to investigate the effects of NACs when co-cultured with S. mutans on cariogenic properties and virulence …

Development Of Loop-Mediated Isothermal Amplification For Rapid Detection Of Fungi In Peritoneal Dialysis, Tamonwan Chamroensakchai

Chulalongkorn University Theses and Dissertations (Chula ETD)

Fungal peritonitis (FP) is a fatal complication in peritoneal dialysis (PD). Detection of fungal infection using standard culture is time-consuming and has a low sensitivity. While, Polymerase Chain Reaction (PCR) are often inapplicable in remote hospital and laboratory. In this study, Loop-mediated Isothermal Amplification (LAMP) assay was developed for rapid and specific detection of fungi in peritoneal dialysis. LAMP primers were designed based on the conserved sequence of fungal 18s rRNA gene. The reaction was optimized for 60 min at 64 ◦C. The sensitivity of LAMP assay was 1 pg/reaction which is a hundred times more sensitive than that of …

Ischemic Stroke Alters Immune Cell Niche And Chemokine Profile In Mice Independent Of Spontaneous Bacterial Infection, Breanne Y. Farris, Kelly L. Monaghan, Wen Zheng, Courtney D. Amend, Heng Hu, Amanda G. Ammer, James E. Coad, Xuefang Ren, Edwin C. K. Wan

Faculty & Staff Scholarship

Background

The aim of this study is to report the long-term efficacy and safety of thoracoscopic epicardial left atrial ablation (TELA) in patients with paroxysmal atrial fibrillation (AF).

Methods

This was a retrospective review of medical records. We included all patients diagnosed with paroxysmal AF who underwent TELA at our institution between 04/2011 and 06/2017. TELA included pulmonary vein isolation, LA dome lesions and LA appendage exclusion. All (n = 55) patients received an implantable loop recorder (ILR), 30 days post-operatively. Antiarrhythmic and anticoagulation therapy were discontinued at 90 and 180 days postoperatively, respectively, if patients were free of …

The Incidence Of Antibiotic-Resistant Staphylococcus Spp. Colonization And Infection In Children And Adults With Atopic Dermatitis, Matchima Laowansiri

Chulalongkorn University Theses and Dissertations (Chula ETD)

Atopic dermatitis (AD) is an inflammatory skin disease characterized by chronic and recurrent eczematous rash. AD occurs in both children and adults, but children are more affected. An important aggravating factor is caused by Staphylococcus aureus (S. aureus) infection. Therefore, topical (beta-lactam, macrolides, clindamycin) and systemic (mupirocin and fusidic acid) antibiotics are essential for treatment of AD. However, frequent use of antibiotics results in an increase in the incidence of antibiotic-resistant S. aureus. Methicillin resistance S. aureus (MRSA) becomes a problem in the treatment of skin diseases. It’s found that the change from penicillin binding protein (PBP) to PBP2a with …

The Incidence Of Antibiotic-Resistant Staphylococcus Spp. Colonization And Infection In Children And Adults With Atopic Dermatitis, Matchima Laowansiri

Chulalongkorn University Theses and Dissertations (Chula ETD)

Atopic dermatitis (AD) is an inflammatory skin disease characterized by chronic and recurrent eczematous rash. AD occurs in both children and adults, but children are more affected. An important aggravating factor is caused by Staphylococcus aureus (S. aureus) infection. Therefore, topical (beta-lactam, macrolides, clindamycin) and systemic (mupirocin and fusidic acid) antibiotics are essential for treatment of AD. However, frequent use of antibiotics results in an increase in the incidence of antibiotic-resistant S. aureus. Methicillin resistance S. aureus (MRSA) becomes a problem in the treatment of skin diseases. It’s found that the change from penicillin binding protein (PBP) to PBP2a with …

The Microbiomes Of Pancreatic And Duodenum Tissue Overlap And Are Highly Subject Specific But Differ Between Pancreatic Cancer And Non-Cancer Subjects, Erika Del Castillo, Richard Meier, Mei Chung, Devin C. Koestler, Tsute Chen, Bruce J. Paster, Kevin P. Charpentier, Karl T. Kelsey, Jacques Izard, Dominique S. Michaud

Department of Food Science and Technology: Faculty Publications

Background: In mice, bacteria from the mouth can translocate to the pancreas and impact pancreatic cancer progression. In humans, oral bacteria associated with periodontal disease have been linked to pancreatic cancer risk. It is not known if DNA bacterial profiles in the pancreas and duodenum are similar within individuals.

Methods: Tissue samples were obtained from 50 subjects with pancreatic cancer or other conditions requiring foregut surgery at the Rhode Island Hospital (RIH), and from thirty-four organs obtained from the National Disease Research Interchange. 16S rRNA gene sequencing was performed on 189 tissue samples (pancreatic duct, duodenum, pancreas), 57 …

Identification Of Probiotic Bacteria With Anticancer Activity Against Colorectal Cancer In Vitro, Patcharin Prakobwat

Chulalongkorn University Theses and Dissertations (Chula ETD)

Colorectal cancer is the third most common cause of cancer death worldwide. It is ranked third for new cancer patients in Thailand. Colorectal cancer is associated with multifactorial risk factors including the imbalance of gut microbiota. This project aimed to identify Lactobacillus strains isolated from Thai healthy populations that have anticancer activities against colorectal cancer in vitro. Lactobacillus cultured media (LCM) obtained from thirty-nine Lactobacillus strains, previously shown to have anti-inflammatory activity, were selected and used at different concentrations and/or pH adjustment to determine the anti-proliferative effect on HT-29 and Caco-2 colon cancer cells at 24, 48, and 72 h. …

Characterization Of Protein Involved In Hemolysis Expressed By Sneathia Amnii, A Pathogen Of The Female Urogenital Tract, Gabriella Gentile, Lizette Carrasco, Amy Stanford, Kimberly Jefferson

Graduate Research Posters

Sneathia amnii is a poorly characterized gram-negative anaerobe that commonly colonizes the vagina. It has been linked to many obstetric disorders, including preterm labor, preeclampsia, and chorioamnionitis. S. amnii lyses human red blood cells, and we aimed to identify the hemolysin. We identified two genes that appear to encode transporter and effector components of a two-partner secretion system. The putative effector, which we refer to as SaFHA, contains a domain with amino acid similarity to the filamentous hemagglutinin (FHA) of Bordetella pertussis and its predicted structure suggests it may form a transmembrane channel or pore. Thus, we hypothesized that SaFHA …

Development Of Improved Acellular Pertussis Vaccines Through Inclusion Of The Rtx Antigen Or Induction Of Mucosal Immunity, Dylan Tyler Boehm

Graduate Theses, Dissertations, and Problem Reports (ETD)

Pertussis is a human respiratory disease, primarily caused by the Gram-negative pathogen Bordetella pertussis. The infection is most severe and can be life-threatening in young children and infants where it manifests as a series of paroxysmal coughs. The disease is more commonly known as whooping cough, due to the whoop omitted during a massive inspiratory effort to bring air back into the lungs. Pertussis is a toxin-mediated disease that persists due to an early release of toxins that allow that bacteria to evade the cells of the innate immune response. The inhibition of the host response continues as toxin activity …

Conjugated Bile Acid And Sphingosine 1-Phosophate Prompt Cholangiocarcinoma Cell Growth Via Releasing Exosomes, Waad A. Alruwaili

Theses and Dissertations

Cholangiocarcinoma (CCA) is a fatal primary malignancy that is formed in the bile ducts. Cancer-associated myofibroblasts play a crucial role in CCA proliferation and invasion. Furthermore, there is a growing interest in the role of the exosome in the interaction between the cancer-associated myofibroblasts and cholangiocarcinoma which lead to CCA growth. However how cholangiocarcinoma-derived exosome affect the cancer-associated myofibroblasts in the tumor microenvironment remain unknown. In this study, we examined whether exosome produced by cholangiocarcinoma could involve in the prompt of CCA cells growth by regulation of myofibroblast. We found that cholangiocarcinoma-derived exosome could prompt elevated α-smooth muscle actin and …

Factors Affecting Biofilm Formation In Oral Pathogenic Bacteria Of The Red Complex, Sidney Nechacov

Theses and Dissertations (Comprehensive)

Periodontal disease, also known as periodontitis, is a dental disease that is estimated to affect 2.4 billion people worldwide. This disease is characterized by chronic inflammation and bleeding of gums, as well as loss of tooth bone density. Currently, treatments for the disease include dental surgeries and various types of antibiotics, but few are targeted specifically at the Red Complex bacteria which are strongly associated with chronic periodontitis. The Red Complex consists of three bacteria: Tannerella forsythia, Porphyromonas gingivalis and Treponema denticola. Each of these bacteria, are anaerobic oral pathogens that reside in the subgingival pocket adjacent to …

Trypanosoma Brucei Prmt1 Is A Nucleic Acid Binding Protein With A Role In Energy Metabolism And The Starvation Stress Response., Lucie Kafková, Chengjian Tu, Kyle L. Pazzo, Kyle P. Smith, Erik W. Debler, Kimberly S. Paul, Jun Qu, Laurie K. Read

Department of Biochemistry and Molecular Biology Faculty Papers

In Trypanosoma brucei and related kinetoplastid parasites, transcription of protein coding genes is largely unregulated. Rather, mRNA binding proteins, which impact processes such as transcript stability and translation efficiency, are the predominant regulators of gene expression. Arginine methylation is a posttranslational modification that preferentially targets RNA binding proteins and is, therefore, likely to have a substantial impact on T. brucei biology. The data presented here demonstrate that cells depleted of T. brucei PRMT1 (TbPRMT1), a major type I protein arginine methyltransferase, exhibit decreased virulence in an animal model. To understand the basis of this phenotype, quantitative global proteomics was employed …

Impact Of Individual Traits, Saturated Fat, And Protein Source On The Gut Microbiome., Jennifer M Lang, Calvin Pan, Rita M Cantor, W H Wilson Tang, Jose Carlos Garcia-Garcia, Ira Kurtz, Stanley L Hazen, Nathalie Bergeron, Ronald M Krauss, Aldons J Lusis

Faculty Publications & Research of the TUC College of Pharmacy

Interindividual variation in the composition of the human gut microbiome was examined in relation to demographic and anthropometric traits, and to changes in dietary saturated fat intake and protein source. One hundred nine healthy men and women aged 21 to 65, with BMIs of 18 to 36, were randomized, after a two-week baseline diet, to high (15% total energy [E])- or low (7%E)-saturated-fat groups and randomly received three diets (four weeks each) in which the protein source (25%E) was mainly red meat (beef, pork) (12%E), white meat (chicken, turkey) (12%E), and nonmeat sources (nuts, beans, soy) (16%E). Taxonomic characterization using …

Virulence Regulation In Pseudomonas Aeruginosa Via The Alginate Regulators, Algu And Algr, The Posttranscriptional Regulator, Rsma, And The Two-Component System, Algz/R, Sean Stacey

Electronic Theses and Dissertations

Pseudomonas aeruginosa is a Gram-negative bacillus able to colonize a wide variety of environments. In the human host, P. aeruginosa can establish an acute infection or persist and create a chronic infection. P. aeruginosa is able to establish a niche and persist in human hosts by using a wide array of virulence factors used for: movement, killing host cells, and evading immune cells and antibiotics. Understanding virulence factors and their regulation has proved to be an important means of combating the morbidity and mortality of P. aeruginosa as well as the ever-increasing threat of drug resistance. By targeting virulence factors …

Dna Methylation By Restriction Modification Systems Affects The Global Transcriptome Profile In Borrelia Burgdorferi, Timothey Casselli, Yvonne Tourand, Adam Scheidegger, William K. Arnold, Anna Proulx, Brian Stevenson, Catherine A. Brissette

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Prokaryote restriction modification (RM) systems serve to protect bacteria from potentially detrimental foreign DNA. Recent evidence suggests that DNA methylation by the methyltransferase (MTase) components of RM systems can also have effects on transcriptome profiles. The type strain of the causative agent of Lyme disease, Borrelia burgdorferi B31, possesses two RM systems with N6-methyladenosine (m6A) MTase activity, which are encoded by the bbe02 gene located on linear plasmid lp25 and bbq67 on lp56. The specific recognition and/or methylation sequences had not been identified for either of these B. burgdorferi MTases, and it was not previously known whether these RM …

Floxed-Cassette Allelic Exchange Mutagenesis Enables Markerless Gene Deletion In Chlamydia Trachomatis And Can Reverse Cassette-Induced Polar Effects, Gabrielle Keb, Robert Hayman, Kenneth A. Fields

Microbiology, Immunology, and Molecular Genetics Faculty Publications

As obligate intracellular bacteria, Chlamydia spp. have evolved numerous, likely intricate, mechanisms to create and maintain a privileged intracellular niche. Recent progress in elucidating and characterizing these processes has been bolstered by the development of techniques enabling basic genetic tractability. Florescence-reported allelic exchange mutagenesis (FRAEM) couples chromosomal gene deletion with the insertion of a selection cassette encoding antibiotic resistance and green fluorescent protein (GFP). Similar to other bacteria, many chlamydial genes exist within polycistronic operons, raising the possibility of polar effects mediated by insertion cassettes. Indeed, FRAEM-mediated deletion of Chlamydia trachomatis tmeA negatively impacts the expression of tmeB. We …

Sumo-Mediated Regulation Of Nlrp3 Modulates Inflammasome Activity., Rachael Barry, Sidonie Wicky John, Gianmaria Liccardi, Tencho Tenev, Isabel Jaco, Chih-Hong Chen, Justin Choi, Paulina Kasperkiewicz, Teresa Fernandes-Alnemri, Emad S Alnemri, Marcin Drag, Yuan Chen, Pascal Meier

Department of Biochemistry and Molecular Biology Faculty Papers

The NLRP3 inflammasome responds to infection and tissue damage, and rapidly escalates the intensity of inflammation by activating interleukin (IL)-1β, IL-18 and cell death by pyroptosis. How the NLRP3 inflammasome is negatively regulated is poorly understood. Here we show that NLRP3 inflammasome activation is suppressed by sumoylation. NLRP3 is sumoylated by the SUMO E3-ligase MAPL, and stimulation-dependent NLRP3 desumoylation by the SUMO-specific proteases SENP6 and SENP7 promotes NLRP3 activation. Defective NLRP3 sumoylation, either by NLRP3 mutation of SUMO acceptor lysines or depletion of MAPL, results in enhanced caspase-1 activation and IL-1β release. Conversely, depletion of SENP7 suppresses NLRP3-dependent ASC oligomerisation, …

Non-Neutralizing Antibodies Elicited By Recombinant Lassa-Rabies Vaccine Are Critical For Protection Against Lassa Fever., Tiago Abreu-Mota, Katie R. Hagen, Kurt Cooper, Peter B. Jahrling, Gene Tan, Christoph Wirblich, Reed F. Johnson, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Lassa fever (LF), caused by Lassa virus (LASV), is a viral hemorrhagic fever for which no approved vaccine or potent antiviral treatment is available. LF is a WHO priority disease and, together with rabies, a major health burden in West Africa. Here we present the development and characterization of an inactivated recombinant LASV and rabies vaccine candidate (LASSARAB) that expresses a codon-optimized LASV glycoprotein (coGPC) and is adjuvanted by a TLR-4 agonist (GLA-SE). LASSARAB elicits lasting humoral response against LASV and RABV in both mouse and guinea pig models, and it protects both guinea pigs and mice against LF. We …

A Virus-Encoded Type I Interferon Decoy Receptor Enables Evasion Of Host Immunity Through Cell-Surface Binding., Bruno Hernáez, Juan Manuel Alonso-Lobo, Imma Montanuy, Cornelius Fischer, Sascha Sauer, Luis J. Sigal, Noemí Sevilla, Antonio Alcamí

Department of Microbiology and Immunology Faculty Papers

Soluble cytokine decoy receptors are potent immune modulatory reagents with therapeutic applications. Some virus-encoded secreted cytokine receptors interact with glycosaminoglycans expressed at the cell surface, but the biological significance of this activity in vivo is poorly understood. Here, we show the type I interferon binding protein (IFNα/βBP) encoded by vaccinia and ectromelia viruses requires of this cell binding activity to confer full virulence to these viruses and to retain immunomodulatory activity. Expression of a variant form of the IFNα/βBP that inhibits IFN activity, but does not interact with cell surface glycosaminoglycans, results in highly attenuated viruses with a virulence similar …

Antibody Epitope Specificity For Dsdna Phosphate Backbone Is An Intrinsic Property Of The Heavy Chain Variable Germline Gene Segment Used, Tatjana Srdic-Rajic, Heinz Kohler, Vladimir Jurisic, Radmila Metlas

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Analysis of protein sequences by the informational spectrum method (ISM) enables characterization of their specificity according to encoded information represented with defined frequency (F). Our previous data showed that F(0.367) is characteristic for variable heavy chain (VH) domains (a combination of variable (V), diversity (D) and joining (J) gene segments) of the anti-phosphocholine (PC) T15 antibodies and mostly dependent on the CDR2 region, a site for PC phosphate group binding. Because the T15 dsDNA-reactive U4 mutant also encodes F(0.367), we hypothesized that the same frequency may also be characteristic for anti-DNA antibodies. Data obtained from an analysis of 60 spontaneously …

Vancomycin Delays Clindamycin-Induced Fatality In The Hamster Model Of Clostridioides [Clostridium] Difficile Infection, Amelia E. Fox-King, Chrisabelle Mefferd, Jacqueline R. Phan, Nancy O. Nou, Ernesto Abel-Santos, Brian P. Hedlund

LSAMP Poster Presentations

Antibiotics can leave the host gut microbiome susceptible to Clostridioides [Clostridium] difficile colonization and lethal toxin production. For instance, clindamycin-induced susceptibility to C. difficile infection (CDI) results in rapid fatality in hamster models, yet vancomycin has been shown to offer increased survival in hamsters challenged with C. difficile. We aim to develop an antibiotic treatment that will facilitate CDI susceptibility without prompt fatality in hamster models. An antibiotic regimen starting with a continuous vancomycin treatment along with a single clindamycin dosage is thought to reduce the major disruption in the indigenous gut microbiome and prevent clindamycin-induced death. …

Detection Of (1,3)-Β-D-Glucan In Cerebrospinal Fluid In Histoplasma Meningitis, Thein Myint, Felicia C. Chow, Karen C. Bloch, Luke Raymond-Guillen, Thomas E. Davis, Patty W. Wright, Laila Woc-Colburn, Raed N. Khairy, Alan C. Street, Tomotaka Yamamoto, Amanda Albers, L. Joseph Wheat, Chadi A. Hage

Internal Medicine Faculty Publications

The diagnosis of central nervous system (CNS) histoplasmosis is often difficult. Although cerebrospinal fluid (CSF) (1,3)-β-d-glucan (BDG) is available as a biological marker for the diagnosis of fungal meningitis, there are limited data on its use for the diagnosis of Histoplasma meningitis. We evaluated CSF BDG detection, using the Fungitell assay, in patients with CNS histoplasmosis and controls. A total of 47 cases and 153 controls were identified. The control group included 13 patients with a CNS fungal infection other than histoplasmosis. Forty-nine percent of patients with CNS histoplasmosis and 43.8% of controls were immunocompromised. The median CSF …

Polymicrobial Sepsis Influences Nk-Cell-Mediated Immunity By Diminishing Nk-Cell-Intrinsic Receptor-Mediated Effector Responses To Viral Ligands Or Infections., Isaac J. Jensen, Christina S. Winborn, Micaela G. Fosdick, Peng Shao, Mikaela M. Tremblay, Qiang Shan, Sandeep Kumar Tripathy, Christopher M. Snyder, Hai-Hui Xue, Thomas S. Griffith, Jon C. Houtman, Vladimir P. Badovinac

Department of Microbiology and Immunology Faculty Papers

The sepsis-induced cytokine storm leads to severe lymphopenia and reduced effector capacity of remaining/surviving cells. This results in a prolonged state of immunoparalysis, that contributes to enhanced morbidity/mortality of sepsis survivors upon secondary infection. The impact of sepsis on several lymphoid subsets has been characterized, yet its impact on NK-cells remains underappreciated-despite their critical role in controlling infection(s). Here, we observed numerical loss of NK-cells in multiple tissues after cecal-ligation-and-puncture (CLP)-induced sepsis. To elucidate the sepsis-induced lesions in surviving NK-cells, transcriptional profiles were evaluated and indicated changes consistent with impaired effector functionality. A corresponding deficit in NK-cell capacity to produce …