Medical Microbiology Commons^™

Improved Database Filtering Technology Enables More Efficient Ab Initio Design Of Potent Peptides Against Ebola Viruses, Thomas Ripperda, Yangsheng Yu, Atul Verma, Elizabeth Klug, Michellie Thurman, St. Patrick Reid, Guangshun Wang

Journal Articles: Pathology and Microbiology

The rapid mutations of viruses such as SARS-CoV-2 require vaccine updates and the development of novel antiviral drugs. This article presents an improved database filtering technology for a more effective design of novel antiviral agents. Different from the previous approach, where the most probable parameters were obtained stepwise from the antimicrobial peptide database, we found it possible to accelerate the design process by deriving multiple parameters in a single step during the peptide amino acid analysis. The resulting peptide DFTavP1 displays the ability to inhibit Ebola virus. A deviation from the most probable peptide parameters reduces antiviral activity. The designed …

Biofilms: Formation, Research Models, Potential Targets, And Methods For Prevention And Treatment, Yajuan Su, Jaime T. Yrastorza, Mitchell Matis, Jenna Cusick, Siwei Zhao, Guangshun Wang, Jingwei Xie

Journal Articles: Pathology and Microbiology

Due to the continuous rise in biofilm-related infections, biofilms seriously threaten human health. The formation of biofilms makes conventional antibiotics ineffective and dampens immune clearance. Therefore, it is important to understand the mechanisms of biofilm formation and develop novel strategies to treat biofilms more effectively. This review article begins with an introduction to biofilm formation in various clinical scenarios and their corresponding therapy. Established biofilm models used in research are then summarized. The potential targets which may assist in the development of new strategies for combating biofilms are further discussed. The novel technologies developed recently for the prevention and treatment …

The Challenges Of Combatting Antimicrobial Resistance In The Philippines, Janine Patricia G. Robredo, Michelle Ann B. Eala, Joseph A. Paguio, Maria Sonia S. Salamat, Leo Anthony G. Celi

Ateneo School of Medicine and Public Health Publications

No abstract provided.

Factors Associated With Hpv16 Cervical Precancerous Stage : Microbiome/Virome And Hpv16 E1, Thanayod Sasivimolrattana

Chulalongkorn University Theses and Dissertations (Chula ETD)

The human papillomavirus type 16 (HPV16) and/or high-risk (Hr-) HPV are the main causes of cervical cancer. The viral factors, such as the E6 and E7 oncogenes, have been recognized as the major factors of carcinogenesis. However, it is currently unknown how other HPV genes, particularly E1, contribute to the development of cancer. Beside HPV, another element that may contribute to the development of cervical cancer is the microbiota in the cervix. Cervical bacteriome and mycobiome have been the focus of numerous investigations; less is known about cervical virome, particularly when HPV is present. No study has investigated the entire …

Predicting Cancer Immunotherapy Response From Gut Microbiomes Using Machine Learning Models, Hai Liang, Jay-Hyun Jo, Zhiwei Zhang, Margaret A Macgibeny, Jungmin Han, Diana M Proctor, Monica E Taylor, You Che, Paul Juneau, Andrea B Apolo, John A Mcculloch, Diwakar Davar, Hassane M Zarour, Amiran K Dzutsev, Isaac Brownell, Giorgio Trinchieri, James L Gulley, Heidi H Kong

Faculty, Staff and Student Publications

Cancer immunotherapy has significantly improved patient survival. Yet, half of patients do not respond to immunotherapy. Gut microbiomes have been linked to clinical responsiveness of melanoma patients on immunotherapies; however, different taxa have been associated with response status with implicated taxa inconsistent between studies. We used a tumor-agnostic approach to find common gut microbiome features of response among immunotherapy patients with different advanced stage cancers. A combined meta-analysis of 16S rRNA gene sequencing data from our mixed tumor cohort and three published immunotherapy gut microbiome datasets from different melanoma patient cohorts found certain gut bacterial taxa correlated with immunotherapy response …

Functional Analysis Of Laminin Subunit Beta-3 (Lamb3) In Hpv16 Positive Cervical Cancer Cell Lines, Warattaya Wattanathavorn

Chulalongkorn University Theses and Dissertations (Chula ETD)

Nearly 100% cervical cancer cases are infected with high-risk (HR) HPV types, in which HR-HPV16 is found in >50%. The mechanism of cervical cell transformation is related to the powerful activity of viral E6 and E7 oncoproteins. The aim of this study is to identify key genes and their associated pathways through comprehensive bioinformatics analysis as well as to explore the effects of a significant gene in cervical cancer carcinogenesis. In this study, the transcriptome sequencing (RNA-seq) of HPV16 positive cervical cancer cell lines (SiHa and CaSki) was compared to HPV negative cervical cancer cell lines (C33A) to identify significant …

Microbial Contamination And Metabolite Exposure Assessment During Waste And Recyclable Material Collection, Fabiola Salambaga, Loïc Wingert, Isabelle Valois, Nancy Lacombe, François Gouin, Julien Trépanier, Maximilien Debia, Ewelina Soszczyńska, Magdalena Twarużek, Robert Kosicki, Marta Dias, Susana Viegas, Liliana Caetano, Carla Viegas, Geneviève Marchand

Études primaires

Waste workers are exposed to bioaerosols when handling, lifting and dumping garbage. Bioaerosol exposure has been linked to health problems such as asthma, airway irritant symptoms, infectious, gastrointestinal and skin diseases, and cancer. Our objective was to characterize the exposure of urban collectors and drivers to inhalable bioaerosols and to measured the cytotoxic effect of air samples in order to evaluate their health risk.

Personal and ambient air sampling were conducted during the summer of 2019. Workers from 12 waste trucks collecting recyclables, organic waste or compost were evaluated. Bacteria and fungi were cultured, molecular biology methods were used to …

Small Bowel Stomas Are Associated With Higher Risk Of Circulating Food-Specific-Igg Than Patients With Organic Gastrointestinal Conditions And Colostomies, Walker K. Carson, Joseph L. Baumert, Jennifer Clarke, Jacques Izard

Department of Food Science and Technology: Faculty Publications

Objective The effects of food sensitivity can easily be masked by other digestive symptoms in ostomates and are unknown. We investigated food-specific-IgG presence in ostomates relative to participants affected by other digestive diseases.

Design Food-specific-IgG was evaluated for 198 participants with a panel of 109 foods. Immunocompetency status was also tested. Jejunostomates, ileostomates, and colostomates were compared with individuals with digestive tract diseases with inflammatory components (periodontitis, eosinophilic esophagitis, duodenitis, ulcerative colitis, Crohn’s disease, and appendicitis), as well as food malabsorption due to intolerance. A logistic regression model with covariates was used to estimate the effect of the experimental data …

Embryonic Hypotaurine Levels Contribute To Strain-Dependent Susceptibility In Mouse Models Of Valproate-Induced Neural Tube Defects, John W Steele, Ying Linda Lin, Nellie Chen, Bogdan J Wlodarczyk, Qiuying Chen, Nabeel Attarwala, Madhu Venkatesalu, Robert M Cabrera, Steven S Gross, Richard H Finnell

Faculty, Staff and Students Publications

Valproic acid (VPA, valproate, Depakote) is a commonly used anti-seizure medication (ASM) in the treatment of epilepsy and a variety of other neurological disorders. While VPA and other ASMs are efficacious for management of seizures, they also increase the risk for adverse pregnancy outcomes, including neural tube defects (NTDs). Thus, the utility of these drugs during pregnancy and in women of childbearing potential presents a continuing public health challenge. Elucidating the underlying genetic or metabolic risk factors for VPA-affected pregnancies may lead to development of non-teratogenic ASMs, novel prevention strategies, or more targeted methods for managing epileptic pregnancies. To address …

Synthetic Flavonoid Derivatives With Antiviral Activity Against Dengue And Chikungunya Viruses, Van Cao

Chulalongkorn University Theses and Dissertations (Chula ETD)

Dengue infection is one significant global health issue, as climate change exacerbated the spread of mosquito vectors. The Chikungunya virus is also a re-emerging arbovirus infection, which is transmitted by some similar vectors. Currently, no commercial antiviral drug is available to treat them. Previous reports suggested that several flavonoid derivatives inhibited mosquito-borne flaviviruses even at submicromolar levels, and one of them is a halogenated flavone derivative, 8-bromobaicalein, was a potential dengue and Zika replication inhibitor targeting flaviviral polymerase and also 3CLpro of SARS-CoV-2. This study characterized that 8-bromobaicalein inhibited chikungunya virus replication with EC50 of 0.49 ± 0.11 µM in …

Effect Of Candida Glabrata Β-Glucans On Immunosuppressive Properties Of Dendritic Cells, Phawida Tummamunkong

Chulalongkorn University Theses and Dissertations (Chula ETD)

β-glucan is a polysaccharide and consists of the backbone of β-(1, 3)-glucan and/or β-(1, 6)-glucan structures. β-glucans are extracted from the cell wall of Candida sp, including Candida glabrata. Interestingly, the biological activity of Candida β-glucan has been represented as a stimulator in the mechanism of immune responses. Dendritic cells are powerful antigen-presenting cells that play a significant role in both innate and adaptive immunity. In the present study, we evaluated the effect of C. glabrata β-glucans on dendritic cell (DC) immunologic responses. Firstly, bone marrow-derived DCs (BMDCs) were induced with C. glabrata β-glucans in a dose-dependent manner. The expression …

Generation Of Tolerogenic Dendritic Cells From Fcgr2b Deficient Lupus-Prone Mice For The Model Of Sle Therapy, Phuriwat Khiewkamrop

Chulalongkorn University Theses and Dissertations (Chula ETD)

Tolerogenic dendritic cells (tolDCs) are DCs with an immunoregulatory function, which can induce regulatory T cells (Tregs) and suppress the immune response. Currently, tolDCs-based treatment has become a promising therapeutic approach for organ transplantation and autoimmune disease. FcgRIIB is an inhibitory receptor widely expressed in B cells, myeloid cells, and DCs. The ablation of FcgRIIB in the murine model shows a spontaneous development of a lupus-like disease and might affect other immune cell regulation. There was limited information on tolDC induction in FcgRIIB defective mice. Thus, in this study, we studied the generation of tolDCs from the bone marrow-derived dendritic …

The Inhibitory Effect Of Combined Human Cathelicidin With Antibiotics On Antibiotic-Resistant Cutibacterium Acnes, Rakwaree Sriharat

Chulalongkorn University Theses and Dissertations (Chula ETD)

Cutibacterium acnes is one of the major factors involved in the pathogenesis of acne vulgaris which sometimes develops antibiotic resistance particularly clindamycin- and doxycycline-resistant C. acnes. In this study, human cathelicidin (LL-37) which is a type of human antimicrobial peptide against a wide range of microorganisms was used. We investigated the antimicrobial activity of LL-37 on C. acnes isolated from patients with acne at the King Chulalongkorn Hospital using broth microdilution. Moreover, the synergistic effects of LL-37 with clindamycin and doxycycline were investigated using checkerboard microdilution, and time-killing assays. The cytotoxicity of LL-37 was also evaluated by MTT assay. The …

Decoding The Mystery Of Antibiotic Persistence, Tahmina Hossain

Electronic Theses and Dissertations

This work combines microbiology, molecular biology, Next-Generation Sequencing and system biology approaches to explore the mechanism of antibiotic persistence: a multi-drug tolerant, non-dividing, and metabolically altered state present in a subpopulation of cells due to phenotypic diversity rather than genetic variation (i.e. mutations). Persister can survive lethal antibiotic state and resuscitate after the treatment period is over. They are considered as the major contributing factor behind recurring infections. They also have a high mutation rate, which increases the chances of bacteria gaining antibiotic resistance. The formation of this phenotypic variant (persister) threatens the therapeutic effectiveness of antibiotics and understanding how …

Effects Of Gaba On Inflammation And Intestinal Barrier Disruption, Tyrel W. Long

EWU Masters Thesis Collection

Gut dysbiosis and intestinal barrier disruption have been linked to multiple sclerosis (MS). Our previous works show that experimental autoimmune encephalomyelitis (EAE) induction modifies the gut's microbiota composition, reducing frequencies of gamma-aminobutyric acid (GABA)-producing bacteria. GABA levels are reduced in the brains and circulation of MS patients. We engineered Lactococcus lactis with extra copies of gadB (glutamic acid decarboxylase) and gadC (glutamate/GABA antiporter) to increase GABA levels produced by the bacterium (GAD-L. lactis). EAE studies showed that the treatment with GAD-L. lactis and not with a L. lactis control expressing an empty plasmid (P-L. lactis) reduced the severity of the …

Oscillations Of The Circadian Clock Protein, Bmal-1, Align To Daily Cycles Of Mechanical Stimuli: A Novel Means To Integrate Biological Time Within Predictive In Vitro Model Systems, Hannah K Heywood, Laurence Gardner, Martin M Knight, David A Lee

Faculty, Staff and Student Publications

PURPOSE: In vivo, the circadian clock drives 24-h rhythms in human physiology. Isolated cells in vitro retain a functional clockwork but lack necessary timing cues resulting in the rapid loss of tissue-level circadian rhythms. This study tests the hypothesis that repeated daily mechanical stimulation acts as a timing cue for the circadian clockwork. The delineation and integration of circadian timing cues into predictive in vitro model systems, including organ-on-a-chip (OOAC) devices, represent a novel concept that introduces a key component of in vivo physiology into predictive in vitro model systems.

METHODS: Quiescent bovine chondrocytes were entrained for 3 days by …

Incfv Plasmid Ped208: Sequence Analysis And Evidence For Translocation Of Maintenance/Leading Region Proteins Through Diverse Type Iv Secretion Systems, Abu Amar M Al Mamun, Kimberly Kissoon, Kouhei Kishida, William C Shropshire, Blake Hanson, Peter J Christie

Faculty, Staff and Student Publications

Two phylogenetically distantly-related IncF plasmids, F and pED208, serve as important models for mechanistic and structural studies of F-like type IV secretion systems (T4SSFs) and F pili. Here, we present the pED208 sequence and compare it to F and pUMNF18, the closest match to pED208 in the NCBI database. As expected, gene content of the three cargo regions varies extensively, although the maintenance/leading regions (MLRs) and transfer (Tra) regions also carry novel genes or motifs with predicted modulatory effects on plasmid stability, dissemination and host range. By use of a Cre recombinase assay for translocation (CRAfT), we recently reported that …

Critical Analysis Of Laboratory Requisition Forms Received In A Cytopathology Laboratory Of A Tertiary Care Centre: An Audit And Review Of Literature, Shivali Sehgal, Sujata Jetley, Zeeba S Jairajpuri, Sabina Khan

Faculty, Staff and Student Publications

BACKGROUND: A laboratory requisition form (LRF) is the main communication link between the laboratories and the clinicians. In a cytopathology laboratory, incomplete forms with inadequate information significantly impact the quality of the results and waste precious time of the lab.

AIMS: The aim of this study was to audit the LRFs for adequacy of demographic and clinical data and to analyze the reasons for the same.

SETTINGS AND DESIGN: A retrospective study was conducted in the cytopathology laboratory of a tertiary care center.

MATERIALS AND METHODS: All the original LRFs received for Pap smears and FNACs of 1-month duration were …

Radiofrequency Ablation In Combination With Cd73 Inhibitor Ab680 Reduces Tumor Growth And Enhances Anti-Tumor Immunity In A Syngeneic Model Of Pancreatic Ductal Adenocarcinoma, Erika Y Faraoni, Lincoln N Strickland, Baylee J O'Brien, Joseph F Barraza, Nirav C Thosani, Curtis J Wray, Tingting W Mills, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma presents a 5-year overall survival rate of 11%, placing an imperative need for the discovery and application of innovative treatments. Radiofrequency ablation represents a promising therapy for PDA, as studies show it induces coagulative necrosis and a host adaptive immune response. In this work we evaluated the effects of RFA treatment in vivo by establishing a syngeneic mouse model of PDA and performing tumor ablation in one flank. Our studies revealed RFA acutely impaired PDA tumor growth; however, such effects were not sustained one week after treatment. Adenosine (ADO) pathway represents a strong immunosuppressive mechanism that was …

Single-Cell Rna Sequencing Reveals Intratumoral Heterogeneity And Potential Mechanisms Of Malignant Progression In Prostate Cancer With Perineural Invasion, Bao Zhang, Shenghan Wang, Zhichao Fu, Qiang Gao, Lin Yang, Zhentao Lei, Yuqiang Shi, Kai Le, Jie Xiong, Siyao Liu, Jiali Zhang, Junyan Su, Jing Chen, Mengyuan Liu, Beifang Niu

Faculty, Staff and Student Publications

Background: Prostate cancer (PCa) is the second most common cancer among men worldwide. Perineural invasion (PNI) was a prominent characteristic of PCa, which was recognized as a key factor in promoting PCa progression. As a complex and heterogeneous disease, its true condition is difficult to explain thoroughly with conventional bulk RNA sequencing. Thus, an improved understanding of PNI-PCa progression at the single-cell level is needed.

Methods: In this study, we performed scRNAseq on tumor tissues of three PNI-PCa patients. Principal component analysis (PCA) and Uniform manifold approximation and projection (UMAP) were used to reduce dimensionality and visualize the cellular composition …