Differential Expression of lncRNAs in HIV Patients with TB and HIV-TB with Anti-Retroviral Treatment.

Tuberculosis (TB) is the leading cause of death among people with HIV-1 infection. To improve the diagnosis and treatment of HIV-TB patients, it is important to understand the mechanisms underlying these conditions. Here, we used an integrated genomics approach to analyze and determine the lncRNAs that are dysregulated in HIV-TB patients and HIV-TB patients undergoing anti-retroviral therapy (ART) using a dataset available in the public domain.

The candidate vaccine derived from H37Rv is markedly immunogenic in macrophages and induces robust immunity to tuberculosis in mice.

Tuberculosis (TB) remains a significant global health challenge, with approximately 1.5 million deaths per year. The Bacillus Calmette-Guérin (BCG) vaccine against TB is used in infants but shows variable protection.

Live Attenuated Vaccines against Tuberculosis: Targeting the Disruption of Genes Encoding the Secretory Proteins of Mycobacteria.

Tuberculosis (TB), a chronic infectious disease affecting humans, causes over 1.3 million deaths per year throughout the world. The current preventive vaccine BCG provides protection against childhood TB, but it fails to protect against pulmonary TB.

Pathogenic mycoplasmas of humans regulate the long noncoding RNAs in epithelial cells.

Non-coding RNAs (ncRNAs), specifically long ncRNAs (lncRNAs), regulate cellular processes by affecting gene expression at the transcriptional, post-transcriptional, and epigenetic levels. Emerging evidence indicates that pathogenic microbes dysregulate the expression of host lncRNAs to suppress cellular defense mechanisms and promote survival. To understand whether the pathogenic human mycoplasmas dysregulate host lncRNAs, we infected HeLa cells with (Mg) and (Mp) and assessed the expression of lncRNAs by directional RNA-seq analysis.

Mycobacterium smegmatis secreting methionine sulfoxide reductase A (MsrA) modulates cellular processes in mouse macrophages.

Methionine sulfoxide reductase A (MsrA) is an antioxidant repair enzyme that reduces the oxidized methionine (Met-O) in proteins to methionine (Met). Its pivotal role in the cellular processes has been well established by overexpressing, silencing, and knocking down MsrA or deleting the gene encoding MsrA in several species. We are specifically interested in understanding the role of secreted MsrA in bacterial pathogens.

The Identification and Clinical Applications of Mutated Antigens in the Era of Immunotherapy.

The era of personalized cancer therapy is here. Advances in the field of immunotherapy have paved the way for the development of individualized neoantigen-based therapies that can translate into favorable treatment outcomes and fewer side effects for patients. Addressing challenges related to the identification, access, and clinical application of neoantigens is critical to accelerating the development of individualized immunotherapy for cancer patients.

Harnessing the Immune System with Cancer Vaccines: From Prevention to Therapeutics.

Prophylactic vaccination against infectious diseases is one of the most successful public health measures of our lifetime. More recently, therapeutic vaccination against established diseases such as cancer has proven to be more challenging. In the host, cancer cells evade immunologic regulation by multiple means, including altering the antigens expressed on their cell surface or recruiting inflammatory cells that repress immune surveillance.

and Regulate a Distinct Set of Protein-Coding Genes in Epithelial Cells.

and are two significant mycoplasmas that infect the urogenital and respiratory tracts of humans. Despite distinct tissue tropisms, they both have similar pathogenic mechanisms and infect/invade epithelial cells in the respective regions and persist within these cells. However, the pathogenic mechanisms of these species in terms of bacterium-host interactions are poorly understood.

Ethanol in Combination with Oxidative Stress Significantly Impacts Mycobacterial Physiology.

Here, we investigate the mycobacterial response to the combined stress of an organic oxidant (cumene hydroperoxide [CHP]) and a solvent (ethanol). To understand the interaction between the two stressors, we treated cells to a range of ethanol concentrations (2.5% to 10% [vol/vol]) in combination with a subinhibitory concentration of 1 mM CHP.

Methionine sulfoxide reductase A (MsrA) modulates cells and protects against Mycoplasma genitalium induced cytotoxicity.

Methionine sulfoxide reductase A (MsrA) is a ubiquitous antioxidant repair enzyme which specifically reduces the oxidized methionine (Met-O) in proteins to methionine (Met). Previous studies have shown that lack of or overexpression of MsrA in cells affects the function of proteins and can lead to altered cellular processes. Interestingly, some pathogenic bacteria secrete and/or carry MsrA on their surface, suggesting some key roles for this enzyme in the modulation of host cellular processes.

An autophagy-inducing and TLR-2 activating BCG vaccine induces a robust protection against tuberculosis in mice.

BCG is widely used as a vaccine against tuberculosis due to (Mtb), which kills millions of people each year. BCG variably protects children, but not adults against tuberculosis. BCG evades phagosome maturation, autophagy, and reduces MHC-II expression of antigen-presenting cells (APCs) affecting T-cell activation.

Utility of OhrR-Ohr system for the expression of recombinant proteins in mycobacteria and for the delivery of M. tuberculosis antigens to the phagosomal compartment.

We have recently reported that in vitro and intracellular organic peroxide stress oxidizes OhrR of Mycobacterium smegmatis and that the oxidized OhrR consequently derepresses the expression of Ohr. Here we demonstrate that the OhrR-Ohr system is highly useful for the expression of recombinant mycobacterial proteins and also for the delivery of Mycobacterium tuberculosis (Mtb) antigens to the phagosomal compartments. Recombinant M.

Enhanced delivery of Mycobacterium tuberculosis antigens to antigen presenting cells using RVG peptide.

Among the various strategies to improve vaccines against infectious diseases, targeting of antigens to dendritic cells (DCs), which are professional antigen presenting cells (APCs), has received increased attention in recent years. Here, we investigated whether a synthetic peptide region named RVG, originated from Rabies Virus Glycoprotein that binds to the α-7 subunit of the nicotinic acetylcholine receptors (AchR-α7) of APCs, could be used for the delivery of Mycobacterium tuberculosis (Mtb) peptide antigens to DCs and macrophages. Mouse bone marrow derived DCs (BMDCs) and human THP-1 macrophages stimulated with RVG fused peptide epitopes 85B and 85B (represent Ag85B and Ag85B, respectively) from antigen 85B (Ag85B) of Mtb showed enhanced antigen presentation as compared to unfused peptide epitopes and BCG.

OhrR of Mycobacterium smegmatis senses and responds to intracellular organic hydroperoxide stress.

Organic hydroperoxide reductase regulator (OhrR) in bacteria is a sensor for organic hydroperoxide stress and a transcriptional regulator for the enzyme organic hydroperoxide reductase (Ohr). In this study we investigated, using a GFP reporter system, whether Mycobacterium smegmatis OhrR has the ability to sense and respond to intracellular organic hydroperoxide stress. It was observed that M.

Recombinant Bacillus subtilis spores for the delivery of Mycobacterium tuberculosis Ag85B-CFP10 secretory antigens.

Tuberculosis continues to be a great cause of morbidity and mortality in different parts of the world. Unfortunately, the current BCG vaccine being administered is not fully protective against tuberculosis; therefore, there is a great need for alternate vaccines. With an aim to develop such vaccines, we have analyzed the utility of Bacillus subtilis spores for the expression of two major immunodominant antigens of Mycobacterium tuberculosis, Ag85B and CFP10.

Modulation of Host miRNAs by Intracellular Bacterial Pathogens.

MicroRNAs (miRNAs) are short non-coding RNAs that regulate the expression of protein coding genes of viruses and eukaryotes at the post-transcriptional level. The eukaryotic genes regulated by miRNAs include those whose products are critical for biological processes such as cell proliferation, metabolic pathways, immune response, and development. It is now increasingly recognized that modulation of miRNAs associated with biological processes is one of the strategies adopted by bacterial pathogens to survive inside host cells.

Inactivation of the organic hydroperoxide stress resistance regulator OhrR enhances resistance to oxidative stress and isoniazid in Mycobacterium smegmatis.

The organic hydroperoxide stress resistance regulator (OhrR) is a MarR type of transcriptional regulator that primarily regulates the expression of organic hydroperoxide reductase (Ohr) in bacteria. In mycobacteria, the genes encoding these proteins exist in only a few species, which include the fast-growing organism Mycobacterium smegmatis. To delineate the roles of Ohr and OhrR in defense against oxidative stress in M.

Mycoplasma genitalium promotes epithelial crossing and peripheral blood mononuclear cell infection by HIV-1.

Background: Mycoplasma genitalium co-infection in HIV-infected individuals has been reported to increase the shedding of HIV in the urogenital region of females. To better understand this relationship, we investigated the influence of M. genitalium on the transmission and replication of HIV using an in vitro model.

Epidemiologic investigation of tuberculosis in a Mexican population from Chihuahua State, Mexico: a pilot study.

Tuberculosis (TB) and its co-morbid conditions have become a burden on global health economies. It is well understood that susceptibility of the host to TB infection/disease is influenced by both genetic and environmental factors and their interactions. The aims of this pilot case-control study are to characterize the sociodemographic and environmental factors related to active TB disease (TB/case) and latent TB infection (LTBI/control) status, and to identify risk factors associated with progression from LTBI to TB.

Differential expression of miRNAs by macrophages infected with virulent and avirulent Mycobacterium tuberculosis.

MicroRNAs (miRNAs) are small non-coding RNAs which post-transcriptionally regulate a wide range of biological processes that include cellular differentiation, development, immunity and apoptosis. There is a growing body of evidences that bacteria modulate immune responses by altering the expression of host miRNAs. Since macrophages are immune cells associated with innate and adaptive immunity, we investigated whether Mycobacterium tuberculosis infection affects miRNAs of macrophages.

A serine/threonine phosphatase encoded by MG_207 of Mycoplasma genitalium is critical for its virulence.

Background: Bacterial signal transduction systems like two component system (TCS) and Serine/Threonine kinase (STK) and Serine/Threonine phosphatase (STP) play important roles in the virulence and pathogenesis of bacterial pathogens. Mycoplasma genitalium, a mollicute that causes the urogenital diseases urethritis and cervicitis in men and women, respectively, is a pathogen which lacks TCS but possesses STK/STP. In this study, we investigated the biochemical and virulence properties of an STP protein encoded by the gene MG_207 of this species.

The fbpA/sapM double knock out strain of Mycobacterium tuberculosis is highly attenuated and immunogenic in macrophages.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is the leading cause of death due to bacterial infections in mankind, and BCG, an attenuated strain of Mycobacterium bovis, is an approved vaccine. BCG sequesters in immature phagosomes of antigen presenting cells (APCs), which do not fuse with lysosomes, leading to decreased antigen processing and reduced Th1 responses. However, an Mtb derived ΔfbpA attenuated mutant underwent limited phagosome maturation, enhanced immunogenicity and was as effective as BCG in protecting mice against TB.

Methionine sulfoxide reductase A (MsrA) deficient Mycoplasma genitalium shows decreased interactions with host cells.

Mycoplasma genitalium is an important sexually transmitted pathogen that affects both men and women. In genital-mucosal tissues, it initiates colonization of epithelial cells by attaching itself to host cells via several identified bacterial ligands and host cell surface receptors. We have previously shown that a mutant form of M.