Predictive biomarkers for latent Mycobacterium tuberculosis infection.

Tuberculosis is a leading cause of infectious death worldwide, with almost a fourth of the world's population latently infected with its causative agent, Mycobacterium tuberculosis. Current diagnostic methods are insufficient to differentiate between healthy and latently infected populations. Here, we used a machine learning approach to analyze publicly available proteomic data from saliva and serum in Ethiopia's healthy, latent TB (LTBI) and active TB (ATBI) people.

Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia.

Purpose: This study was conducted to investigate the drug resistance mutations and genetic diversity of HIV-1 in ART experienced patients in South Omo, Ethiopia.

Patients And Methods: A cross-sectional study conducted on 253 adult patients attending ART clinics for ≥6 months in South Omo. Samples with VL ≥1000 copies/mL were considered as virological failures (VF) and their reverse transcriptase gene codons 90-234 were sequenced using Illumina MiSeq.

Urethral Catheter Biofilms Reveal Plasticity in Bacterial Composition and Metabolism and Withstand Host Immune Defenses in Hypoxic Environment.

Biofilms composed of multiple microorganisms colonize the surfaces of indwelling urethral catheters that are used serially by neurogenic bladder patients and cause chronic infections. Well-adapted pathogens in this niche are , and spp., species that cycle through adhesion and multilayered cell growth, trigger host immune responses, are starved off nutrients, and then disperse.

Protein and Microbial Biomarkers in Sputum Discern Acute and Latent Tuberculosis in Investigation of Pastoral Ethiopian Cohort.

Differential diagnosis of tuberculosis (TB) and latent TB infection (LTBI) remains a public health priority in high TB burden countries. Pulmonary TB is diagnosed by sputum smear microscopy, chest X-rays, and PCR tests for distinct () genes. Clinical tests to diagnose LTBI rely on immune cell stimulation in blood plasma with TB-specific antigens followed by measurements of interferon-γ concentrations.

Differences in plasma proteomes for active tuberculosis, latent tuberculosis and non-tuberculosis mycobacterial lung disease patients with and without ESAT-6/CFP10 stimulation.

Background: Tuberculosis (TB) is one of the world's most problematic infectious diseases. The pathogen Mycobacterium tuberculosis (Mtb) is contained by the immune system in people with latent TB infection (LTBI). No overt disease symptoms occur.

Molecular epidemiology of clinical Mycobacterium tuberculosis complex isolates in South Omo, Southern Ethiopia.

Background: Tuberculosis (TB) is caused by Mycobacterium tuberculosis complex (MTBC). Mapping the genetic diversity of MTBC in high TB burden country like Ethiopia is important to understand principles of the disease transmission and to strengthen the regional TB control program. The aim of this study was to investigate the genetic diversity of Mycobacterium tuberculosis complex (MTBC) isolates circulating in the South Omo, southern Ethiopia.

Protein signatures from blood plasma and urine suggest changes in vascular function and IL-12 signaling in elderly with a history of chronic diseases compared with an age-matched healthy cohort.

Key processes characterizing human aging are immunosenescence and inflammaging. The capacity of the immune system to adequately respond to external perturbations (e.g.

Gut Microbial Changes in Diabetic db/db Mice and Recovery of Microbial Diversity upon Pirfenidone Treatment.

The leptin receptor-deficient db/db mouse model is an accepted in vivo model to study obesity, type 2 diabetes, and diabetic kidney disease. Healthy gastrointestinal (GI) microbiota has been linked to weight loss, improved glycemic control, and physiological benefits. We investigated the effect of various drugs on the GI microbiota of db/db mice as compared to control db/m mice.

Persistent Gut Microbial Dysbiosis in Children with Acute Lymphoblastic Leukemia (ALL) During Chemotherapy.

Prophylactic or therapeutic antibiotic use along with chemotherapy treatment potentially has a long-standing adverse effect on the resident gut microbiota. We have established a case-control cohort of 32 pediatric and adolescent acute lymphoblastic leukemia (ALL) patients and 25 healthy siblings (sibling controls) to assess the effect of chemotherapy as well as antibiotic prophylaxis on the gut microbiota. We observe that the microbiota diversity and richness of the ALL group is significantly lower than that of the control group at diagnosis and during chemotherapy.

Gastro-intestinal and oral microbiome signatures associated with healthy aging.

The human oral and gut microbiomes influence health via competition for a distinct niche in the body with pathogens, via metabolic capabilities that increase host digestive capacity and generate compounds engaged in signaling pathways and modulation of immune system functions. Old age alters our metabolic and regenerative capacity. Following recruitment of 65 human subjects in the age range of 70 to 82, we discerned healthy aging (HA) and non-healthy aging (NHA) cohorts discordant in the occurrence of one or more major diseases: (1) cancer, (2) acute or chronic cardiovascular diseases, (3) acute or chronic pulmonary diseases, (4) diabetes, and (5) stroke or neurodegenerative disorders.

Using Proteomics to Identify Inflammation During Urinary Tract Infection.

Urinary tract infections (UTIs) are one of the most common bacterial infections. Conventional approaches to diagnose these infections rely on microbial urine culture, urine sediment microscopy and basic molecular urinalysis tests, in combination with assessments of patient symptoms that are indicative of UTI. The last decade has seen a more widespread clinical use of standardized MALDI-TOF methods to identify UTI-causing microbial agents.

Detection of Neutrophil Extracellular Traps in Urine.

Neutrophils are important mediators of the antimicrobial defense during urinary tract infections (UTIs). When activated at the site of infection, these innate immune cells phagocytose and neutralize an invading pathogen. Another neutrophil defense strategy is the release of effectors, such as antimicrobial peptides and proteins stored in neutrophil granules and reactive oxygen species.

Proteome Profiled in Polymicrobial Urethral Catheter Biofilms.

, a Gram-positive anaerobic coccoid rod colonizing the human urinary tract, belongs to the taxonomic class of Actinobacteria. We identified as a cohabitant of urethral catheter biofilms (CB). The CBs also harbored more common uropathogens, such as and , supporting the notion that is adapted to a life style in polymicrobial biofilms.

Phenotypic and genotypic drug sensitivity of complex isolated from South Omo Zone, Southern Ethiopia.

Background: Knowledge of drug-sensitivity patterns of complex (MTBC) strains isolated from patients is an important aspect of TB control strategy. This study was conducted to evaluate the drug sensitivity of MTBC isolates in South Omo, southern Ethiopia.

Materials And Methods: A total of 161 MTBC isolates (153 from new cases and eight re-treatment TB cases) were isolated using Lowenstein Jensen medium of which 126 isolates were able to be tested for drug sensitivity by BACTEC™MGIT™ 960 system, while all the 161 isolates were tested by GenoType MTBDR VER 2.

ProteoStorm: An Ultrafast Metaproteomics Database Search Framework.

Shotgun metaproteomics has the potential to reveal the functional landscape of microbial communities but lacks appropriate methods for complex samples with unknown compositions. In the absence of prior taxonomic information, tandem mass spectra would be searched against large pan-microbial databases, which requires heavy computational workload and reduces sensitivity. We present ProteoStorm, an efficient database search framework for large-scale metaproteomics studies, which identifies high-confidence peptide-spectrum matches (PSMs) while achieving a two-to-three orders-of-magnitude speedup over popular tools.

S-Trap, an Ultrafast Sample-Preparation Approach for Shotgun Proteomics.

The success of shotgun proteomic analysis depends largely on how samples are prepared. Current approaches (such as those that are gel-, solution-, or filter-based), although being extensively employed in the field, are time-consuming and less effective with respect to the repetitive sample processing, recovery, and overall yield. As an alternative, the suspension trapping (S-Trap) filter has been commercially available very recently in the format of a single or 96-well filter plate.

Microbial metagenome of urinary tract infection.

Urine culture and microscopy techniques are used to profile the bacterial species present in urinary tract infections. To gain insight into the urinary flora, we analyzed clinical laboratory features and the microbial metagenome of 121 clean-catch urine samples. 16S rDNA gene signatures were successfully obtained for 116 participants, while metagenome sequencing data was successfully generated for samples from 49 participants.

Latent tuberculosis infection and associated risk indicators in pastoral communities in southern Ethiopia: a community based cross-sectional study.

Background: Research pertaining to the community-based prevalence of latent tuberculosis infection (LTBI) is important to understand the magnitude of this infection. This study was conducted to estimate LTBI prevalence and to identify associated risk factors in the Omo Zone of Southern Ethiopia.

Methods: A community-based cross-sectional study was conducted in six South Omo districts from May 2015 to February 2016.

Potential Immunological Biomarkers for Detection of Mycobacterium tuberculosis Infection in a Setting Where M. tuberculosis Is Endemic, Ethiopia.

Accurate diagnosis and early treatment of tuberculosis (TB) and latent TB infection (LTBI) are vital to prevent and control TB. The lack of specific biomarkers hinders these efforts. This study's purpose was to screen immunological markers that discriminate infection outcomes in a setting where it is endemic, Ethiopia.

Mechanisms of action of Coxiella burnetii effectors inferred from host-pathogen protein interactions.

Coxiella burnetii is an obligate Gram-negative intracellular pathogen and the etiological agent of Q fever. Successful infection requires a functional Type IV secretion system, which translocates more than 100 effector proteins into the host cytosol to establish the infection, restructure the intracellular host environment, and create a parasitophorous vacuole where the replicating bacteria reside. We used yeast two-hybrid (Y2H) screening of 33 selected C.

Type 1 Diabetes: Urinary Proteomics and Protein Network Analysis Support Perturbation of Lysosomal Function.

While insulin replacement therapy restores the health and prevents the onset of diabetic complications (DC) for many decades, some T1D patients have elevated hemoglobin A1c values suggesting poor glycemic control, a risk factor of DC. We surveyed the stool microbiome and urinary proteome of a cohort of 220 adolescents and children, half of which had lived with T1D for an average of 7 years and half of which were healthy siblings. Phylogenetic analysis of the 16S rRNA gene did not reveal significant differences in gut microbial alpha-diversity comparing the two cohorts.

Nontuberculosis mycobacteria are the major causes of tuberculosis like lesions in cattle slaughtered at Bahir Dar Abattoir, northwestern Ethiopia.

Background: The main cause of bovine tuberculosis (bTB) is believed to be Mycobacterium bovis (M. bovis). Nontuberculosis mycobacteria (NTM) are neglected but opportunistic pathogens and obstacles for bTB diagnosis.

Quick 96FASP for high throughput quantitative proteome analysis.

Unlabelled: Filter aided sample preparation (FASP) is becoming a central method for proteomic sample cleanup and peptide generation prior to LC-MS analysis. We previously adapted this method to a 96-well filter plate, and applied to prepare protein digests from cell lysate and body fluid samples in a high throughput quantitative manner. While the 96FASP approach is scalable and can handle multiple samples simultaneously, two key advantages compared to single FASP, it is also time-consuming.

Molecular typing of Mycobacterium tuberculosis complex isolated from pulmonary tuberculosis patients in central Ethiopia.

Background: Identification of the types of strains of Mycobacterium tuberculosis (M. tuberculosis) complex causing tuberculosis (TB) could contribute to TB control program of specific geographic region as well as it could add knowledge onto the existing literature on TB worldwide. The objective of the present study was to identify the species and strains of M.