Antitubercular Activity of 7-Methyljuglone-Loaded Poly-(Lactide Co-Glycolide) Nanoparticles.

Background/objectives: Loading of natural products into poly-(lactide-co-glycolic) acid (PLGA) nanoparticles as drug delivery systems for the treatment of diseases, such as tuberculosis (TB), has been widely explored. The current study investigated the use of PLGA nanoparticles with 7-methyljuglone (7-MJ), an active pure compound, isolated from the roots of A. DC.

Complete genome sequences of mycobacteriophages Ashwin from cluster O and Chanagan from cluster A1.

Ashwin and Chanagan are double-stranded mycobacteriophages isolated from a single soil sample from a lavender flowerpot in Johannesburg, South Africa. Both are capable of infecting and lyzing and are predicted to contain 122 and 91 open reading frames, respectively, most without known function.

Complete genome sequence of Wildflower, an O cluster mycobacteriophage.

Wildflower is a cluster O mycobacteriophage with a siphoviral morphotype that displays lytic activity in . It was isolated from soil in Johannesburg, South Africa. The double-stranded genome consists of 69,364 base pairs with a GC content of 65.

Collaborative learning in the digital age: empowering tuberculosis researchers through virtual training.

Integrating whole genome sequencing (WGS) of the complex into routine care, surveillance, and research in high tuberculosis burden settings remains challenging due to limited resources and skills. While technological platforms for scaling WGS are emerging, scaling wet lab and analytic components often depends on partnerships where such skills have been established. To address this, a virtual training program was developed.

The effect of previous SARS-CoV-2 infection on systemic immune responses in individuals with tuberculosis.

Background: The impact of previous SARS-CoV-2 infection on the systemic immune response during tuberculosis (TB) disease has not been explored.

Methods: An observational, cross-sectional cohort was established to evaluate the systemic immune response in persons with pulmonary tuberculosis with or without previous SARS-CoV-2 infection. Those participants were recruited in an outpatient referral clinic in Rio de Janeiro, Brazil.

Clinical Strains of Representing Different Genotype Families Exhibit Distinct Propensities to Adopt the Differentially Culturable State.

Growing evidence points to the presence of differentially culturable tubercle bacteria (DCTB) in clinical specimens from individuals with active tuberculosis (TB) disease. These bacteria are unable to grow on solid media but can resuscitate in liquid media. Given the epidemiological success of certain clinical genotype families of , we hypothesize that different strains may have distinct mechanisms of adaptation and tolerance.

A modified BCG with depletion of enzymes associated with peptidoglycan amidation induces enhanced protection against tuberculosis in mice.

Mechanisms by which (Mtb) evades pathogen recognition receptor activation during infection may offer insights for the development of improved tuberculosis (TB) vaccines. Whilst Mtb elicits NOD-2 activation through host recognition of its peptidoglycan-derived muramyl dipeptide (MDP), it masks the endogenous NOD-1 ligand through amidation of glutamate at the second position in peptidoglycan side-chains. As the current BCG vaccine is derived from pathogenic mycobacteria, a similar situation prevails.

Development of primer-probe sets to rapidly distinguish single nucleotide polymorphisms in SARS-CoV-2 lineages.

Ongoing SARS-CoV-2 infections are driven by the emergence of various variants, with differential propensities to escape immune containment. Single nucleotide polymorphisms (SNPs) in the RNA genome result in altered protein structures and when these changes occur in the -gene, encoding the spike protein, the ability of the virus to penetrate host cells to initiate an infection can be significantly altered. As a result, vaccine efficacy and prior immunity may be diminished, potentially leading to new waves of infection.

challenge models for infectious diseases.

Traditionally, molecular mechanisms of pathogenesis for infectious agents were studied in cell culture or animal models but have limitations on the extent to which the resulting data reflect natural infection in humans. The COVID-19 pandemic has highlighted the urgent need to rapidly develop laboratory models that enable the study of host-pathogen interactions, particularly the relative efficacy of preventive measures. Recently, human and animal tissue challenge models have emerged as a promising avenue to study immune responses, screen potential therapies and triage vaccine candidates.

Production and Performance Assessment of a Severe Acute Respiratory Syndrome Coronavirus 2 Biomimetic in a Verification Program for Pandemic Readiness.

During the early stages of the 2019 coronavirus disease (COVID-19) pandemic in South Africa, one of many challenges included availability of control material for laboratory proficiency testing programs. Proficiency testing control material using live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or RNA extracted from cell culture was either biohazardous or costly, particularly in resource-limited settings. This study reports the development and application of a noninfectious SARS-CoV-2 biomimetic Mycobacterium smegmatis strain that mimics a positive result in the GeneXpert SARS-CoV-2 Xpert Xpress cartridge.

Evaluation of a human mucosal tissue explant model for SARS-CoV-2 replication.

With the onset of COVID-19, the development of ex vivo laboratory models became an urgent priority to study host-pathogen interactions in response to the pandemic. In this study, we aimed to establish an ex vivo mucosal tissue explant challenge model for studying SARS-CoV-2 infection and replication. Nasal or oral tissue samples were collected from eligible participants and explants generated from the tissue were infected with various SARS-CoV-2 strains, including IC19 (lineage B.

The performance of tongue swabs for detection of pulmonary tuberculosis.

Introduction: Oral and/or tongue swabs have demonstrated ability to detect in adults with pulmonary tuberculosis (TB). Swabs provide useful alternative specimens for diagnosis of TB using molecular assays however, the diagnostic pickup by culture requires further improvement and development. Several studies identified the presence of differentially culturable tubercle bacilli (DCTB) populations in a variety of clinical specimens.

Complete genome sequence of Azrael100, a V cluster mycobacteriophage.

Azrael100, a cluster V siphoviral mycobacteriophage, was isolated from a garden in Johannesburg, South Africa. It can infect and lyse mc155. The double-stranded DNA genome contains 78,063 base pairs with a GC content of 56.

Amidation of glutamate residues in mycobacterial peptidoglycan is essential for cell wall cross-linking.

Introduction: Mycobacteria assemble a complex cell wall with cross-linked peptidoglycan (PG) which plays an essential role in maintenance of cell wall integrity and tolerance to osmotic pressure. We previously demonstrated that various hydrolytic enzymes are required to remodel PG during essential processes such as cell elongation and septal hydrolysis. Here, we explore the chemistry associated with PG cross-linking, specifically the requirement for amidation of the D-glutamate residue found in PG precursors.

Opportunities and challenges of leveraging COVID-19 vaccine innovation and technologies for developing sustainable vaccine manufacturing capabilities in Africa.

The COVID-19 pandemic heralded unprecedented resource mobilisation and global scientific collaboration to rapidly develop effective vaccines. Regrettably, vaccine distribution has been inequitable, particularly in Africa where manufacturing capacity remains nominal. To address this, several initiatives are underway to develop and manufacture COVID-19 vaccines in Africa.

Complete Genome Sequence of Lopsy, a B1 Cluster Mycobacteriophage.

Lopsy is a siphovirus mycobacteriophage that is capable of lytic infection in Mycobacterium smegmatis. It is classified as a subcluster B1 mycobacteriophage and was isolated from soil in Estcourt, South Africa. The 68,542-bp double-stranded DNA genome is circularly permuted, has a GC content of 66.

A modified BCG with depletion of enzymes associated with peptidoglycan amidation induces enhanced protection against tuberculosis in mice.

Mechanisms by which (Mtb) evades pathogen recognition receptor activation during infection may offer insights for the development of improved tuberculosis (TB) vaccines. Whilst Mtb elicits NOD-2 activation through host recognition of its peptidoglycan-derived muramyl dipeptide (MDP), it masks the endogenous NOD-1 ligand through amidation of glutamate at the second position in peptidoglycan sidechains. As the current BCG vaccine is derived from pathogenic mycobacteria, a similar situation prevails.

Proteomic Analysis of Mucosal and Systemic Responses to SARS-CoV-2 Antigen.

The mucosal environment of the upper respiratory tract is the first barrier of protection against SARS-CoV-2 transmission. However, the mucosal factors involved in viral transmission and potentially modulating the capacity to prevent such transmission have not fully been identified. In this pilot proteomics study, we compared mucosal and systemic compartments in a South African cohort of vaccinated and unvaccinated individuals undergoing maxillofacial surgery with previous history of COVID-19 or not.

Differentially culturable tubercle bacteria as a measure of tuberculosis treatment response.

Introduction: Routine efficacy assessments of new tuberculosis (TB) treatments include quantitative solid culture or routine liquid culture, which likely miss quantification of drug tolerant bacteria. To improve these assessments, comparative analyses using additional measures such as quantification of differentially culturable tubercle bacteria (DCTB) are required. Essential for enabling this is a comparative measure of TB treatment responses using routine solid and liquid culture with liquid limiting dilutions (LLDs) that detect DCTB in sputum.

Culture filtrate supplementation can be used to improve culture positivity for spinal tuberculosis diagnosis.

Culture remains the gold standard to diagnose spinal tuberculosis (STB) despite the paucibacillary nature of the disease. Current methods can take up to 42 days to yield a result, delaying the ability to rapidly detect drug resistance. Studies have demonstrated the use of supplementation with culture filtrate (CF) from an axenic culture of () as a source of growth factors to improve culture rates.

The detection of mixed tuberculosis infections using culture filtrate and resuscitation promoting factor deficient filtrate.

Tuberculosis (TB) infected individuals harbor a heterogenous population of differentially culturable tubercle bacilli (DCTB). Herein, we describe how DCTB assays using culture filtrate either containing or deficient in resuscitation promoting factors can uncover mixed infections. We demonstrate that () strain genotypes can be separated in DCTB assays based on their selective requirement for growth stimulatory factors.

Survival and detection of SARS-CoV-2 variants on dry swabs post storage.

COVID-19 has resulted in nearly 598 million infections and over 6.46 million deaths since the start of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in 2019. The rapid onset of the pandemic, combined with the emergence of viral variants, crippled many health systems particularly from the perspective of coping with massive diagnostic loads.

Drug resistant tuberculosis: Implications for transmission, diagnosis, and disease management.

Drug resistant tuberculosis contributes significantly to the global burden of antimicrobial resistance, often consuming a large proportion of the healthcare budget and associated resources in many endemic countries. The rapid emergence of resistance to newer tuberculosis therapies signals the need to ensure appropriate antibiotic stewardship, together with a concerted drive to develop new regimens that are active against currently circulating drug resistant strains. Herein, we highlight that the current burden of drug resistant tuberculosis is driven by a combination of ongoing transmission and the intra-patient evolution of resistance through several mechanisms.

Detection of differentially culturable tubercle bacteria in sputum from drug-resistant tuberculosis patients.

Several studies described the presence of non-replicating, drug-tolerant differentially culturable tubercle bacteria (DCTB) in sputum from patients with active tuberculosis (TB). These organisms are unable to form colonies on agar but can be recovered in liquid media supplemented with culture filtrate as a source of growth factors. Herein, we undertook to investigate the response of DCTB during the treatment of individuals with drug-resistant TB.