Life Sciences Commons^™

Ribosome Hibernation Factor Induces Antibiotic Persisters Of Mycobacterium Tuberculosis In Neutrophil-Rich Lung Lesions, Jamie Corro

Electronic Theses & Dissertations (2024 - present)

Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, is a prescient global health threat and the leading cause of death by an infectious agent. Treatment of Mtb infection involves administering 2-4 antibiotics for a minimum of 6 months. This extended drug regimen is required to target a subpopulation of persistent bacilli. As their name implies, these bacteria can “persist” by acquiring nonhereditary and transient antibiotic tolerance. Although the precise mechanism is unknown, it’s often attributed to slowing cellular growth and metabolic processes. During zinc deprivation, bacteria can remodel their ribosomes by replacing their zinc-binding paralogues containing the CXXC motif (C+) …

Metabolomic Insights Into Tuberculosis: Machine Learning Approaches For Biomarker Identification, Miftahul Khair Akbar, Arief Aulia Rahman

Indonesian Journal of Medical Chemistry and Bioinformatics

The lung parenchyma is largely impacted by the infectious condition known as pulmonary tuberculosis (pulmonary TB) when the immune system creates a wall around the germs in the lungs, a tiny, hard bulge known as a tubercle develops, earning the disease the name tuberculosis. Although the majority of TB germs target the lungs, they can also harm other bodily organs. The identification of TB biomarkers, which are crucial for diagnosis, treatment monitoring, risk analysis, and prognosis, has been the subject of extensive research. Differences in metabolites between normal cells and tuberculosis are considered to be able to support the diagnosis …

Testing Of Indazole Inhibitors Of Kasa, A Vital Enzyme Of M. Tuberculosis, Karissa Highlander

Student Research Submissions

Tuberculosis is a disease that affects the lungs caused by Mycobacterium tuberculosis (M. tuberculosis). Although drug treatment options exist, increased rates of antibiotic resistant strains have become more prevalent in recent years, driving a need for new treatment approaches. KasA, a β-ketoacyl synthase, has been found to synthesize parts of the cell wall and been identified as an attractive drug target. Previous medicinal chemistry research has been completed to synthesize six effective competitive inhibitors of KasA that would potentially block the enzyme from binding the substrate, preventing elongation of the backbone and creation of the mycolic fatty acids that …

Ferroptosis Hijacking By Mycobacterium Tuberculosis, Boyi Gan

Student and Faculty Publications

A recent study from Nature Communications reveals that Mycobacterium tuberculosis can hijack epigenetic machinery in host cells and induce host cell ferroptosis, which promotes pathogen pathogenicity and spread. These findings also suggest new therapeutic strategies to treat tuberculosis.

Characterisation Of Drug-Resistant Mycobacterium Tuberculosis Mutations And Transmission In Pakistan, Gary Napier, Anwar Sheed Khan, Abdul Jabbar, Muhammad Tahir Khan, Sajid Ali, Muhammad Qasim, Noor Mohammad, Rumina Hasan, Zahra Hasan, Susana Campino

Department of Pathology and Laboratory Medicine

Tuberculosis, caused by Mycobacterium tuberculosis, is a high-burden disease in Pakistan, with multi-drug (MDR) and extensive-drug (XDR) resistance, complicating infection control. Whole genome sequencing (WGS) of M. tuberculosis is being used to infer lineages (strain-types), drug resistance mutations, and transmission patterns-all informing infection control and clinical decision making. Here we analyse WGS data on 535 M. tuberculosis isolates sourced across Pakistan between years 2003 and 2020, to understand the circulating strain-types and mutations related to 12 anti-TB drugs, as well as identify transmission clusters. Most isolates belonged to lineage 3 (n = 397; 74.2%) strain-types, and were MDR (n = …

Integrated Model Of A Family Approach And Local Support In Tuberculosis Case Finding Efforts In People With Hiv/Aids, Erni Astutik, Chatarina Umbul Wahyuni, Imelda F E Manurung, Geofrey Ssekalembe

Kesmas

The human immunodeficiency virus (HIV) remains a major global public health problem. People with HIV/acquired immune deficiency syndrome (AIDS) are more susceptible to opportunistic infections such as tuberculosis (TB). Therefore, families and community leaders need to help monitor people living with HIV/AIDS (PLWHA). This study aimed to analyze an integrated family approach and local support model to detect TB cases in PLWHA. This study used a case-control study in Kupang City, East Nusa Tenggara Province, in July 2020. The sample comprised 100 people (50 PLWHA with TB case and 50 controls) using total sampling and random sampling, respectively. The variables …

Global, Regional, And National Sex Differences In The Global Burden Of Tuberculosis By Hiv Status, 1990-2019: Results From The Global Burden Of Disease Study 2019, Jorge R. Ledesma, Hmwe Hmwe Kyu, Arianna Maever L. Amit, Veincent Christian F. Pepito, Gbd 2019 Tuberculosis Collaborators, 328 Co-Authors

Ateneo School of Medicine and Public Health Publications

Background

Tuberculosis is a major contributor to the global burden of disease, causing more than a million deaths annually. Given an emphasis on equity in access to diagnosis and treatment of tuberculosis in global health targets, evaluations of differences in tuberculosis burden by sex are crucial. We aimed to assess the levels and trends of the global burden of tuberculosis, with an emphasis on investigating differences in sex by HIV status for 204 countries and territories from 1990 to 2019.

Methods

We used a Bayesian hierarchical Cause of Death Ensemble model (CODEm) platform to analyse 21 505 site-years of vital …

Profiling Pretomanid As A Therapeutic Option For Tb Infection: Evidence To Date., Stephani L. Stancil, Fuad Mirzayev, Susan M. Abdel-Rahman

Manuscripts, Articles, Book Chapters and Other Papers

Tuberculosis (TB) is the most deadly infectious disease globally. Although most individuals achieve a cure, a substantial portion develop multi-drug resistant TB which is exceedingly difficult to treat, and the number of effective agents is dwindling. Development of new anti-tubercular medications is imperative to combat existing drug resistance and accelerate global eradication of TB. Pretomanid (PA-824) represents one of the newest drug classes (ie, nitroimidazooxazines) approved in 2019 by the United States Food and Drug Administration as part of a multi-drug regimen (with bedaquiline and linezolid, BPaL) and recommended by the World Health Organization (WHO) to treat extensively-resistant (XR-TB) and …

Cloning Of Pe11 (Lipx, Rv1169c) Gene Of Mycobacterium Tuberculosis Beijing Strain To Pcdna3.1 Plasmid Vector, Lulut Azmi Supardi, Andriansjah Rukmana, Fithriyah Sjatha

Makara Journal of Science

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. It is a persistent global health problem with a high mortality rate. Currently, TB is controlled by administering the Bacillus Calmette-Guerin (BCG) vaccine, but the effectiveness of its protection varies among individuals in a population. The pe/ppe gene family comprises a typical group of genes that play a role in avoiding the host immune response and inducing persistent TB infection. Based on in silico analysis, the pe11 gene has estimated immunogenicity and potential as a TB seed vaccine candidate. The pe11 gene from an Indonesian isolate of an M. …

Pioneer Science And The Great Plagues: How Microbes, War, And Public Health Shaped Animal Health, Norman F. Cheville, Purdue University Press

Purdue University Press Books

Pioneer Science and the Great Plagues covers the century when infectious plagues—anthrax, tuberculosis, tetanus, plague, smallpox, and polio—were conquered, and details the important role that veterinary scientists played. The narrative is driven by astonishing events that centered on animal disease: the influenza pandemic of 1872, discovery of the causes of anthrax and tuberculosis in the 1880s, conquest of Texas cattle fever and then yellow fever, German anthrax attacks on the United States during World War I, the tuberculin war of 1931, Japanese biological warfare in the 1940s, and today’s bioterror dangers.

Veterinary science in the rural Midwest arose from agriculture, …

Examining Early Interactions Between Innate Airway Resident Immune Cells And Mtb-Specific Factors During Pulmonary Infection With Mycobacterium Tuberculosis, Micah D. Dunlap

Arts & Sciences Electronic Theses and Dissertations

Mycobacterium tuberculosis (Mtb) is the leading cause of death by an infectious agent in the world today, infecting roughly one quarter of humans. Despite this, the mechanisms of early pathogenesis and host protective innate immune responses remain poorly understood and uncharacterized.

Lung resident Alveolar Macrophages (AMs) are the first host contact with Mtb bacilli after inhalation and are thus key mediators of the early pulmonary immune response. AMs are generally believed to reside entirely in the airway, but it was recently demonstrated that they have the capacity to egress and enter into granulomas during pulmonary infection with hypervirulent Mtb. Furthermore, …

Cultural And Religious Belief Approaches Of A Tuberculosis Program For Hard-To-Reach Populations In Mentawai And Solok West Sumatera, Indonesia, Rizanda Machmud, Irvan Medison, Finny Fitry Yani

Kesmas

Tuberculosis (TB) is a leading public health concern in Indonesia. It ranks second on the list of high-burden TB countries. In West Sumatra, 47% of TB cases are undetected, late diagnosed, and received incomplete treatment because of low-level awareness and knowledge and stigma, especially among the hardest to reach populations. The study aims to identify the best communication channel to reach those who live in vulnerable and remote areas. This study was a qualitative study applying in-depth interviews to the informal leaders, health officers, cultural artists, and religious leaders across districts in Mentawai and Solok Districts, which are remote and …

Prevalence Of Tuberculosis In District Haveli, Azad Jammu And Kashmir, Abu Ul Hassan Faiz, Ghazal Tariq, Ayesha Faiz, Lariab Zahra Faiz

Journal of Bioresource Management

Tuberculosis is an infectious disease with a common occurrence in population of Azad Jammu and Kashmir. The current study was designed to find out the prevalence of TB among the general population of a less developed District Haveli. Samples were collected from different hospitals and TB centers located in district Haveli and tested through sputum smear microscopy for conformation of positive for TB. The three-year (2015 to 2018) study was conducted to record prevalence of tuberculosis in selected area of Azad Jammu and Kashmir. The trend line of prevalence was made by using (SPSS software). Results produced linear trends yearly …

Design And Synthesis Of Novel Analogs As Potential Antitubercular Agents, Peggy Mccluggage

Honors Theses

Tuberculosis (TB) is an infectious, airborne disease which primarily infects the lungs. One-third of the world’s population is currently estimated to be infected with Mycobacterium tuberculosis (Mtb), the causative agent for TB [1]. Current treatment for this disease requires at least six months of taking multiple antibiotics with undesirable side effects [2]. Difficulty in complying to this regimen as well as the prevalence of HIV/AIDS has led to antimicrobial resistance seen in Mtb. In order to combat the Multi-Drug Resistant and Extensively-Drug Resistant strains of the disease-causing bacteria, preventative care and novel antibiotics are urgently needed [3]. The purpose for …

Effects Of Inactivated Mycobacterium Bovis Vaccination On Molokai-Origin Wild Pigs Experimentally Infected With Virulent M. Bovis, Pauline Nol, Morgan Wehte, Richard A. Bowen, Suelee Robbe-Austerman, Tyler Thacker, Kristina Lantz, Jack Rhyan, Laurie A. Baeten, Ramón A. Juste, Iker A. Sevilla, Christian Gortazar, Joaquín Vicente

United States Department of Agriculture Wildlife Services: Staff Publications

The wild pig population on Molokai, Hawaii, USA is a possible reservoir for bovine tuberculosis, caused by Mycobacterium bovis, and has been implicated in decades past as the source of disease for the island’s domestic cattle. Heat-inactivated vaccines have been effective for reducing disease prevalence in wild boar in Spain and could prove useful for managing M. bovis in Molokai wild pigs. We designed an experiment to test this vaccine in wild pigs of Molokai genetics. Fifteen 3–4-month-old pigs were orally administered 10⁶–10⁷ colony forming units (cfu) of heat-inactivated M. bovis (Vaccinates; n = 8; 0.2 …

Mycobacterium Tuberculosis Inhibitors: Action And Resistance, Pamela K. Garcia-Moreno

FIU Electronic Theses and Dissertations

Tuberculosis, an infectious disease caused by Mycobacterium tuberculosis, has been a global health problem for years. The emergence of drug resistance in this organism generates the necessity of exploring novel targets and developing new drugs. Topoisomerases are enzymes found in all kingdoms of life responsible for overcoming the topological barriers encountered during essential cellular processes. The genomes of mycobacteria encode only one type IA topoisomerase (MtopI), which has been validated as a novel TB drug target. The goal of this study is to obtain new information on the mechanism and resistance of endogenous and synthetic inhibitors of MtopI.

Rv1495 is …

Identification Of Bhlhe40 And Irg1 As Essential Regulators Of The Inflammatory Response To Mycobacterium Tuberculosis, Jeremy Peter Huynh

Arts & Sciences Electronic Theses and Dissertations

Protective immune responses to Mycobacterium tuberculosis (Mtb) must induce bactericidal functions while minimizing damage to the lung. Such responses require precise control of pro- and anti-inflammatory factors to regulate the recruitment and function of protective immune cells but the mechanisms by which this control is exerted remain incompletely defined. Basic helix-loop-helix family, member e40 (Bhlhe40) is a transcription factor known to regulate production of pro- and anti-inflammatory cytokines that affect protective immunity to Mtb. Immune-responsive Gene 1 (Irg1) is an enzyme that generates itaconate, a metabolite with potential anti-inflammatory and antibacterial roles during Mtb infection. The impact of Bhlhe40 and …

The Pathology Of Tuberculosis Lesions In Allergic Skin Test (Ppd Tuberculin) Positive Cows And Detection Of Tuberculosis Agents With Pcr In Milk Samples, Çi̇ğdem Tuncay, Fati̇h Hati̇poğlu

Turkish Journal of Veterinary & Animal Sciences

The aim of this study was to determine tuberculosis (Tb) agents in milk and the pathologic changes in the tissues and organs of 100 PPD Tb-positive cows that were intended for slaughter. Milk samples were taken before slaughtering and PCR analysis was conducted to detect the Tb agent. In postmortem examinations, the lungs, liver, mammary glands, spleen, kidneys, and heart were collected for macroscopic and histopathological examinations. Out of the 100 PPD positive cows, lesions of Tb were observed in 75 cows. In the microscopic examination, Tb was identified in the lungs (51 cases), liver (61 cases), and in both …

Is Tb Testing Associated With Increased Blood Interferon-Gamma Levels?, Aideen E. Kennedy, Jim O'Mahony, Noel Byrne, John Macsharry, Riona G. Sayers

Department of Biological Sciences Publications

The Republic of Ireland reports a relatively low prevalence of Johne’s disease (JD) compared to international counterparts. Postulated reasons for this include a lower average herd size and a grass-based production system. Ireland also engages in high levels of bovine tuberculosis (bTB) testing. As interferon-gamma (IFN-γ) is believed to play a key role in protecting against JD, it is our hypothesis that administration of purified protein derivative (PPD), as part of the bTB test, is associated with a systemic increase in IFN-γ production, which may potentially limit clinical progression of the disease. We studied 265 cows (202 Friesian and 63 …

Level Of Exposure Of Childhood Tuberculosis With Adult Pulmonary Tuberculosis Household Contacts, Al Asyary, Tris Eryando, Purwantyastuti Purwantyastuti, Purnawan Junadi, Carol Clark, Edwin Van Teijlingen

Kesmas

Tuberkulosis paru (TB) pada anak kian menjadi masalah kesehatan global yang masih terlupakan seiring dengan peningkatan proporsi TB di Indonesia. Penularan penyakit ini di populasi umum seringkali berdampak pada anak, terlebih ketika kontak TB terjadi di rumah tangga. Penelitian ini bertujuan untuk memperoleh faktor protektif sehingga anak tetap sehat meskipun memiliki kontak dengan penderita TB dewasa serumah. Penelitian ini dilakukan dengan pendekatan kasus kontrol pada 132 responden anak yang berasal dari delapan rumah sakit rujukan dan beberapa puskesmas di Provinsi Daerah Istimewa Yogyakarta. Penelitian dilakukan dalam periode Januari hingga Desember 2014 yang hasilnya dianalisis dengan uji bivariat (kai kuadrat) dan …

The Role Of Bhlhe40 In Autoimmune Neuroinflammation And Mycobacterial Infection, Chih-Chung Lin

Arts & Sciences Electronic Theses and Dissertations

The mammalian immune system is composed of innate and adaptive compartments, which cooperate with each other to maintain homeostasis and protect the host from the invasion by a variety of pathogens. The tight control of immune responses is extremely important for all individuals. Here, we discovered that the transcription factor basic helix-loop-helix family, member e40 (Bhlhe40) is a critical protein that regulates the autoimmune ("against self") and anti-microbial ("against non-self") responses of myeloid cells and T lymphocytes. Multiple sclerosis (MS) is a human neuroinflammatory disease in the central nervous system with an autoimmune etiology. We have reported that Bhlhe40 positively …

Determining The Effects Of Methanol, Ethanol, Isopropanol, And Glycerol On Both Thermal Stability And Catalytic Activity Of Rv0045c, An Enzyme From M. Tuberculosis, Katelyn Baumer

Undergraduate Honors Thesis Collection

Tuberculosis (TB) is a highly infectious respiratory disease contracted through the inhalation of Mycobacterium tuberculosis. Serine hydrolases are abundant in M. tuberculosis and serve as a model for studying the inhibition of TB. Rv0045c is an example of such with little known regarding its biological function. Rv0045c was exposed to methanol, ethanol, isopropanol, or glycerol and the effects of varying concentration of these alcohols on the catalytic efficiency and thermal stability of the enzyme was determined. The thermal stability of Rv0045c was found to decrease with concentration of methanol, ethanol, or isopropanol. The opposite was true of the thermal stability …

Tuberculosis In Vulnerable Populations In Eastern Mediterranean Region-Implications For Control, Sadia Shakoor, Rumina Hasan

Department of Pathology and Laboratory Medicine

Objectives: Socially and economically disadvantaged or "vulnerable" people are at high risk of tuberculosis (TB) and also contribute to active chains of TB transmission. Included in such vulnerable populations are children, women, prisoners, people living with human immunodeficiency virus, the homeless, and displaced people. The ongoing active transmission of TB among such populations is made more difficult to assess and control by difficult access, health inequities, poverty, and other chronic and debilitating health conditions at individual, domestic, and community levels.
Methods: The 22 Eastern Mediterranean Region member states encompass diverse sociopolitical and socioeconomic situations with far-reaching effects on vulnerable populations …

Non-Essentiality Of Alr And Muri Genes In Mycobacteria, Philion L. Hoff, Denise Zinniel, Raúl G. Barletta

UCARE Research Products

Amino acids are the building blocks of life. If DNA is the blueprint, amino acids are the lumber that proteins are built with. Proteins are built with left-handed, L- forms of amino acids. Bacteria have an essential cell wall component that happens to be an exception: peptidoglycan. Bacteria have enzymes called racemases that convert L- amino acid forms into right-handed, D- forms. Amino acids participate in many reactions with keto acids. Transaminases allow conversion between amino acids by transfer of an amino group.

Previous reports claimed there is no D-ala transaminase activity in mycobacteria and thus alr and murI genes …

Tuberculosis And Cardiovascular Disease: Linking The Epidemics, Moises A. Huaman, David Henson, Eduardo Ticona, Timothy R. Sterling, Beth A. Garvy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The burden of tuberculosis and cardiovascular disease (CVD) is enormous worldwide. CVD rates are rapidly increasing in low- and middle-income countries. Public health programs have been challenged with the overlapping tuberculosis and CVD epidemics. Monocyte/macrophages, lymphocytes and cytokines involved in cellular mediated immune responses against Mycobacterium tuberculosis are also main drivers of atherogenesis, suggesting a potential pathogenic role of tuberculosis in CVD via mechanisms that have been described for other pathogens that establish chronic infection and latency. Studies have shown a pro-atherogenic effect of antibody-mediated responses against mycobacterial heat shock protein-65 through cross reaction with self-antigens in human vessels. Furthermore, …

Development And Validation Of Sandwich Quantitative Elisa Prototypebased On The Bovine Ifng For The Detection Of Cellular Immunity, Oktay Genç, Özlem Büyüktanir, Gülnur Serdar, Yunus Kiliçoğlu, Sali̇h Otlu

Turkish Journal of Veterinary & Animal Sciences

Immunodiagnostic tests based on in vitro enzymatic methods are mostly preferred to in vivo methods for the detection of cellular immunity due to their cost, applicability, repeatability, and higher sensitivity. Therefore, the development of a quantitative sandwich ELISA prototype detecting bovine IFNg (bIFNg) was planned. In this study, two clone originated monoclonal antibodies were used for capturing the plates, and biotin conjugated monoclonal Ab was used as a secondary antibody in sandwich ELISA. Different approaches such as inter- and intraassay precision and dilution parallelism were evaluated for test validation. The correlation of coefficient variation that is over 95% and 5% …

Peningkatan Determinan Sosial Dalam Menurunkan Kejadian Tuberkulosis Paru, Dyah Wulan Sumekar Rengganis Wardani

Kesmas

Upaya pengendalian tuberkulosis paru oleh World Health Organization telah meningkatkan angka kesembuhan dan menyelamatkan banyak jiwa, tetapi kurang berhasil dalam menurunkan insiden tuberkulosis. Oleh karena itu, pengendalian tuberkulosis akan lebih menekankan pada kebijakan determinan sosial karena determinan sosial secara langsung maupun melalui faktor risiko tuberkulosis berpengaruh terhadap tuberkulosis. Di Bandar Lampung, angka notifikasi tuberkulosis dari tahun 2009 – 2010 mengalami peningkatan walaupun angka kesembuhan sudah lebih dari 85%. Bandar Lampung juga merupakan bagian dari salah satu provinsi termiskin di Indonesia. Penelitian ini bertujuan untuk mempelajari pengaruh determinan sosial (yang diukur melalui indikator pendidikan, pendapatan dan kelas sosial) terhadap kejadian tuberkulosis. …

Diagnosis Dini Tuberkulosis Pada Kontak Serumah Dengan Penderita Tuberkulosis Paru Melalui Deteksi Kadar Ifn-Γ, Sri Andarini Indreswari, Suharyo Suharyo

Kesmas

Tuberkulosis paru masih merupakan masalah dunia. Indonesia menempati peringkat ke tiga di dunia pada tahun 2012. Target nasional Case Detection Rate tahun 2012 adalah 70%, sedangkan pencapaian Jawa Tengah sebesar 58,48%. Penelitian ini bertujuan untuk memperoleh batas kadar interferon (IFN) γ pada orang kontak serumah dengan penderita tuberkulosis paru sebagai dasar diagnosis dini penyakit tuberkulosis. Penelitian dilakukan secara kohort selama dua tahun (2011 - 2013) di Balai Kesehatan Masyarakat Paru Semarang. Pada akhir penelitian, terdapat 12 responden kontak dan 13 tidak kontak serumah. Uji Wilcoxon menunjukkan perbedaan bermakna rerata kadar IFN-γ antara kelompok kontak dengan kelompok tidak kontak serumah (nilai …

Drug Resistant Tuberculosis: Challenges Of Urbanization, Rumina Hasan

Department of Pathology and Laboratory Medicine

No abstract provided.

Interactions Between Human Neutrophils And Mycobacterium Smegmatis : A Comparative General Analysis., Irina Miralda

College of Arts & Sciences Senior Honors Theses

Mycobacteria smegmatis is an abundant soil and water inhabitant with which humans are continuously in contact. Despite the fact that it is typically considered non-­‐pathogenic, a few rare cases of M. smegmatis-­‐caused infections have been reported and it has been shown that M. smegmatis is able to modulate inflammatory responses in macrophages. Neutrophils are the innate immune system’s first line of centralized defense against invading microbes, especially the frequently encountered M. smegmatis. However, very little information is known of the mechanism by which neutrophils eliminate environmental bacteria. In this study, the hypothesis that M. smegmatis regulates neutrophil functional responses, and …