Dissecting Host-Pathogen Interactions in TB Using Systems-Based Omic Approaches

Tuberculosis (TB) is a devastating infectious disease that kills over a million people every year. There is an increasing burden of multi drug resistance (MDR) and extensively drug resistance (XDR) TB. New and improved therapies are urgently needed to overcome the limitations of current treatment. The causative agent, Mycobacterium tuberculosis (Mtb) is one of the most successful pathogens that can manipulate host cell environment for adaptation, evading immune defences, virulence, and pathogenesis of TB infection. Host-pathogen interaction is important to establish infection and it involves a complex set of processes. Metabolic cross talk between the host and pathogen is a facet of TB infection and has been an important topic of research where there is growing interest in developing therapies and drugs that target these interactions and metabolism of the pathogen in the host. Mtb scavenges multiple nutrient sources from the host and has adapted its metabolism to survive in the intracellular niche. Advancements in systems-based omic technologies have been successful to unravel host-pathogen interactions in TB. In this review we discuss the application and usefulness of omics in TB research that provides promising interventions for developing anti-TB therapies.

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Current insights into the chemistry and antitubercular potential of benzimidazole and imidazole derivatives

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666201102094401 ◽

2020 ◽

Vol 20 ◽

Author(s):

Deepa Parwani ◽

Sushanta Bhattacharya ◽

Akash Rathore ◽

Chaitali Mallick ◽

Vivek Asati ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Multi Drug Resistance ◽

Benzimidazole Derivatives ◽

Duration Of Treatment ◽

Structure Activity ◽

Mdr Tb ◽

Low Toxicity ◽

Extensively Drug Resistance ◽

Improved Characteristics

: Tuberculosis is a disease caused by Mycobacterium tuberculosis (Mtb), affecting millions of people worldwide. The emergence of drug resistance is a major problem in the successful treatment of tuberculosis. Due to the commencement of MDR-TB (multi-drug resistance) and XDR-TB (extensively drug resistance), there is a crucial need for the development of novel anti-tubercular agents with improved characteristics such as low toxicity, enhanced inhibitory activity and short duration of treatment. In this direction, various heterocyclic compounds have been synthesized and screened against Mycobacterium tuberculosis. Among them, benzimidazole and imidazole containing derivatives found to have potential anti-tubercular activity. The present review focuses on various imidazole and benzimidazole derivatives (from 2015-2019) with their structure activity relationships in the treatment of tuberculosis.

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Next-generation technologies for studying host–pathogen interactions: a focus on dual transcriptomics, CRISPR/Cas9 screening and organs-on-chips

Pathogens and Disease ◽

10.1093/femspd/ftz060 ◽

2019 ◽

Vol 77 (6) ◽

Author(s):

Buket Baddal

Keyword(s):

Infectious Disease ◽

Drug Targets ◽

Genome Mining ◽

Three Dimensional ◽

Local Environment ◽

Rna Seq ◽

Host Pathogen Interactions ◽

Host Pathogen ◽

On Chip ◽

Organ Models

ABSTRACT Pathogens constantly interact with their hosts and the environment, and therefore have evolved unique virulence mechanisms to target and breach host defense barriers and manipulate host immune response to establish an infection. Advances in technologies that allow genome mining, gene editing such as CRISPR/Cas9, genomic, epigenomic and transcriptomic studies such as dual RNA-seq, coupled with bioinformatics, have accelerated the field of host–pathogen interactions within a broad range of infection models. Underpinning of the molecular changes that accompany invasion of eukaryotic cells with pathogenic microorganisms at the intersection of host, pathogen and their local environment has provided a better understanding of infectious disease mechanisms and antimicrobial strategies. The recent evolution of physiologically relevant three-dimensional (3-D) tissue/organ models and microfluidic organ-on-chip devices also provided a window to a more predictive framework of infectious disease processes. These approaches combined hold the potential to highly impact discovery of novel drug targets and vaccine candidates of the future. Here, we review three of the available and emerging technologies—dual RNA-seq, CRISPR/Cas9 screening and organs-on-chips, applicable to the high throughput study and deciphering of interaction networks between pathogens and their hosts that are critical for the development of novel therapeutics.

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Extra-Pulmonary TB

Advances in Medical Diagnosis, Treatment, and Care - Strategies to Overcome Superbug Invasions ◽

10.4018/978-1-7998-0307-2.ch005 ◽

2021 ◽

pp. 91-116

Author(s):

Sarita Rani ◽

Ankur Kaul ◽

Anil Kumar Mishra ◽

Umesh Gupta

Keyword(s):

Drug Resistance ◽

Polymeric Micelles ◽

New Drugs ◽

Multi Drug Resistance ◽

Liposomal Formulations ◽

Extra Pulmonary ◽

Stability Issues ◽

Low Solubility ◽

Line Drug ◽

Extensively Drug Resistance

Tuberculosis is considered a fatal respiratory disease commonly seen in developing countries. This chapter includes the global scenario of TB patients and brief description of TB history, its pathogenesis, types, diagnosis tests, emergence of MDR (multi drug resistance) and XDR (extensively drug resistance). The traditional chemotherapy of TB includes first and second line drug therapy. These lines of therapies face many difficulties such as low solubility, low bioavailability, and stability issues. Therefore, some new drugs were introduced in the market that showed effective results to the patients. Nanoparticulate drug delivery gained much focus in recent years due to its advantages and ideal characteristics. Numerous nanoparticles, liposomal formulations, and polymeric micelles were reported by the researchers with significant and considerable results. Inhalable formulations were also prepared by scientists that showed effective and remarkable anti-tuberculosis action on TB patients. Many efforts are awaited to completely eradicate TB from the planet.

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Spatial dynamics and genetics of infectious diseases on heterogeneous landscapes

Journal of The Royal Society Interface ◽

10.1098/rsif.2007.1041 ◽

2007 ◽

Vol 4 (16) ◽

pp. 935-948 ◽

Cited By ~ 120

Author(s):

Leslie A Real ◽

Roman Biek

Keyword(s):

Infectious Disease ◽

Spatial Genetic Structure ◽

Management Strategies ◽

Spatial Dynamics ◽

Disease Process ◽

Disease Spread ◽

Host Pathogen Interactions ◽

Host Pathogen ◽

Control And Management ◽

And Control

Explicit spatial analysis of infectious disease processes recognizes that host–pathogen interactions occur in specific locations at specific times and that often the nature, direction, intensity and outcome of these interactions depend upon the particular location and identity of both host and pathogen. Spatial context and geographical landscape contribute to the probability of initial disease establishment, direction and velocity of disease spread, the genetic organization of resistance and susceptibility, and the design of appropriate control and management strategies. In this paper, we review the manner in which the physical organization of the landscape has been shown to influence the population dynamics and spatial genetic structure of host–pathogen interactions, and how we might incorporate landscape architecture into spatially explicit population models of the infectious disease process to increase our ability to predict patterns of disease occurrence and optimally design vaccination and control policies.

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Comparison of Clinical Characteristics between Pulmonary Tuberculosis Patients with Extensively Drug-resistance and Multi-drug Resistance at National Medical Center in Korea

Tuberculosis and Respiratory Diseases ◽

10.4046/trd.2008.64.6.414 ◽

2008 ◽

Vol 64 (6) ◽

pp. 414

Author(s):

Chong Kyung Kim ◽

Ha Do Song ◽

Dong Il Cho ◽

Nam Soo Yoo

Keyword(s):

Drug Resistance ◽

Pulmonary Tuberculosis ◽

Clinical Characteristics ◽

Medical Center ◽

Multi Drug Resistance ◽

Tuberculosis Patients ◽

National Medical ◽

Extensively Drug Resistance

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Modeling Host-Pathogen Interactions in the Context of the Microenvironment: Three-Dimensional Cell Culture Comes of Age

Infection and Immunity ◽

10.1128/iai.00282-18 ◽

2018 ◽

Vol 86 (11) ◽

Cited By ~ 36

Author(s):

Jennifer Barrila ◽

Aurélie Crabbé ◽

Jiseon Yang ◽

Karla Franco ◽

Seth D. Nydam ◽

...

Keyword(s):

Infectious Disease ◽

Historical Context ◽

Three Dimensional ◽

Microbial Pathogens ◽

Host Pathogen Interactions ◽

Commensal Microbiota ◽

Disease Mechanisms ◽

Host Pathogen ◽

Single Cell Type ◽

Biomechanical Forces

ABSTRACTTissues and organs provide the structural and biochemical landscapes upon which microbial pathogens and commensals function to regulate health and disease. While flat two-dimensional (2-D) monolayers composed of a single cell type have provided important insight into understanding host-pathogen interactions and infectious disease mechanisms, these reductionist models lack many essential features present in the native host microenvironment that are known to regulate infection, including three-dimensional (3-D) architecture, multicellular complexity, commensal microbiota, gas exchange and nutrient gradients, and physiologically relevant biomechanical forces (e.g., fluid shear, stretch, compression). A major challenge in tissue engineering for infectious disease research is recreating this dynamic 3-D microenvironment (biological, chemical, and physical/mechanical) to more accurately model the initiation and progression of host-pathogen interactions in the laboratory. Here we review selected 3-D models of human intestinal mucosa, which represent a major portal of entry for infectious pathogens and an important niche for commensal microbiota. We highlight seminal studies that have used these models to interrogate host-pathogen interactions and infectious disease mechanisms, and we present this literature in the appropriate historical context. Models discussed include 3-D organotypic cultures engineered in the rotating wall vessel (RWV) bioreactor, extracellular matrix (ECM)-embedded/organoid models, and organ-on-a-chip (OAC) models. Collectively, these technologies provide a more physiologically relevant and predictive framework for investigating infectious disease mechanisms and antimicrobial therapies at the intersection of the host, microbe, and their local microenvironments.

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Novel Vaccine Candidates against Tuberculosis

Current Medicinal Chemistry ◽

10.2174/0929867326666181126112124 ◽

2020 ◽

Vol 27 (31) ◽

pp. 5095-5118 ◽

Cited By ~ 1

Author(s):

Zhihao Li ◽

Changping Zheng ◽

Marco Terreni ◽

Lisa Tanzi ◽

Matthieu Sollogoub ◽

...

Keyword(s):

Drug Resistance ◽

Clinical Trials ◽

Recent Progress ◽

Multi Drug Resistance ◽

System Response ◽

Bacillus Calmette Guerin ◽

Vaccine Research ◽

Vaccine Candidates ◽

Immune System Response ◽

Extensively Drug Resistance

Ranking above AIDS, Tuberculosis (TB) is the ninth leading cause of death affecting and killing many individuals every year. Drugs’ efficacy is limited by a series of problems such as Multi- Drug Resistance (MDR) and Extensively-Drug Resistance (XDR). Meanwhile, the only licensed vaccine BCG (Bacillus Calmette-Guérin) existing for over 90 years is not effective enough. Consequently, it is essential to develop novel vaccines for TB prevention and immunotherapy. This paper provides an overall review of the TB prevalence, immune system response against TB and recent progress of TB vaccine research and development. Several vaccines in clinical trials are described as well as LAM-based candidates.

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PROGRESS IN COMPUTATIONAL STUDIES OF HOST–PATHOGEN INTERACTIONS

Journal of Bioinformatics and Computational Biology ◽

10.1142/s0219720012300018 ◽

2013 ◽

Vol 11 (02) ◽

pp. 1230001 ◽

Cited By ~ 32

Author(s):

HUFENG ZHOU ◽

JINGJING JIN ◽

LIMSOON WONG

Keyword(s):

Protein Interactions ◽

Computational Studies ◽

Interaction Data ◽

Protein Protein Interactions ◽

Host Pathogen Interactions ◽

Basic Principles ◽

Host Pathogen Interaction ◽

Treatment And Prevention ◽

Host Pathogen ◽

Pathogen Protein

Host–pathogen interactions are important for understanding infection mechanism and developing better treatment and prevention of infectious diseases. Many computational studies on host–pathogen interactions have been published. Here, we review recent progress and results in this field and provide a systematic summary, comparison and discussion of computational studies on host–pathogen interactions, including prediction and analysis of host–pathogen protein–protein interactions; basic principles revealed from host–pathogen interactions; and database and software tools for host–pathogen interaction data collection, integration and analysis.

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