In silico design of multi-epitope adhesin protein vaccines.

(Mtb) adhesin proteins are promising candidates for subunit vaccine design. Multi-epitope Mtb vaccine and diagnostic candidates were designed using immunoinformatic tools. The antigenic potential of 26 adhesin proteins were determined using VaxiJen 2.

A Review Of Host-Specific Diagnostic And Surrogate Biomarkers In Children With Pulmonary Tuberculosis.

Background: Tuberculosis (TB) is one of the most common causes of mortality globally with a steady rise in paediatric cases in the past decade. Laboratory methods of diagnosing TB and monitoring response to treatment have limitations. Current research focuses on interrogating host- and/or pathogen-specific biomarkers to address this problem.

A computational method for the prediction and functional analysis of potential adhesin-related proteins.

Objectives: Mycobacterial adherence plays a major role in the establishment of infection within the host. Adhesin-related proteins attach to host receptors and cell-surface components. The current study aimed to utilize in-silico strategies to determine the adhesin potential of conserved hypothetical (CH) proteins.

M. tuberculosis curli pili (MTP) facilitates a reduction of microbicidal activity of infected THP-1 macrophages during early stages of infection.

Mycobacterium tuberculosis (M. tuberculosis) curli pili (MTP) is a surface located adhesin, which is involved in the initial point-of-contact between the pathogen and the host. Host-pathogen interaction is essential for establishing infection.

Predominance of the Mycobacterium tuberculosis Beijing strain amongst children from a high tuberculosis burden township in South Africa.

The objective was to determine the molecular epidemiology and drug susceptibility patterns of Mycobacterium tuberculosis (MTB) of children and their household contacts (HHC) in Umlazi, a high TB-burden township in South Africa. Sixty eight MTBRifPLUS positive TB-infected children (TIC) (≤14 years) and 111 HHC were enrolled. Drug susceptibility testing (DST) was performed on sputum samples using the proportion method and GenoType® MTBDR.

Genome sequence of a carbapenemase-encoding Acinetobacter baumannii isolate of the sequence type 231 isolated from hospital wastewater in South Africa.

Objectives: The resistome, virulome, mobilome and phylogenetic relationship of the Acinetobacter baumannii isolate FG121 depicting the multilocus sequence type (ST) 231 isolated from hospital effluent water in South Africa was determined using whole-genome sequence analysis.

Method: A. baumannii FG121 was isolated on Leed Acinetobacter Medium (LAM) agar and the bacterial isolate was identified using the VITEK®2 platform.

Antibiotic resistance and biofilm formation of Acinetobacter baumannii isolated from high-risk effluent water in tertiary hospitals in South Africa.

Objectives: Discharge of drug-resistant, biofilm-forming pathogens from hospital effluent water into municipal wastewater treatment plants poses a public health concern. This study examined the relationship between antibiotic resistance levels and biofilm formation of Acinetobacter baumannii strains isolated from hospital effluents.

Methods: Antibiotic susceptibility of 71 A.

M. tuberculosis curli pili (MTP) is associated with alterations in carbon, fatty acid and amino acid metabolism in a THP-1 macrophage infection model.

The initial host-pathogen interaction is crucial for the establishment of infection. An improved understanding of the pathophysiology of Mycobacterium tuberculosis (M. tuberculosis) during macrophage infection can aid the development of intervention therapeutics against tuberculosis.

Light Forge: A Microfluidic DNA Melting-based Tuberculosis Test.

Background: There is a well-documented lack of rapid, low-cost tuberculosis (TB) drug resistance diagnostics in low-income settings across the globe. It is these areas that are plagued with a disproportionately high disease burden and in greatest need of these diagnostics.

Methods: In this study, we compared the performance of Light Forge, a microfluidic high-resolution melting analysis (HRMA) prototype for rapid low-cost detection of TB drug resistance with a commercial HRMA device, a predictive "nearest-neighbor" thermodynamic model, DNA sequencing, and phenotypic drug susceptibility testing (DST).

Immunoscreening of the M. tuberculosis F15/LAM4/KZN secretome library against TB patients' sera identifies unique active- and latent-TB specific biomarkers.

Tuberculosis (TB) protein biomarkers are urgently needed for the development of point-of-care diagnostics, new drugs and vaccines. Mycobacterium tuberculosis extracellular and secreted proteins play an important role in host-pathogen interactions. Antibodies produced against M.

Evaluation of a synthetic peptide for the detection of anti-Mycobacterium tuberculosis curli pili IgG antibodies in patients with pulmonary tuberculosis.

Tuberculosis (TB) remains a serious threat in underdeveloped areas. Mycobacterium tuberculosis curli pili (MTP), a virulence factor, is a potential biomarker for a reliable point of care (POC) test and was evaluated for its ability to react with Immunoglobulin G (IgG) in TB patients. An MTP synthetic peptide in a slot blot assay was used to screen serum/plasma samples (n = 65) in 3 separate cohorts, including 40 TB positive (16 HIV co-infected), 20 TB negative/HIV negative patients and 5 healthy volunteers.

Mycobacterium tuberculosis strains induce strain-specific cytokine and chemokine response in pulmonary epithelial cells.

M. tuberculosis F15/LAM4/KZN has been associated with high transmission rates of drug resistant tuberculosis in the KwaZulu-Natal province of South Africa. The current study elucidated the cytokine/chemokine responses induced by representatives of the F15/LAM4/KZN and other dominant strain families in pulmonary epithelial cells.

Fitness-compensatory mutations facilitate the spread of drug-resistant F15/LAM4/KZN and F28 Mycobacterium tuberculosis strains in KwaZulu-Natal, South Africa.

While the acquisition of drug resistance is often accompanied by fitness costs, Mycobacterium tuberculosis has developed mechanisms to overcome these costs in the form of compensatory mutations. In an attempt to dissect strain-specific differences in biological fitness, 10 M. tuberculosis genomes, representing F15/LAM4/KZN, Beijing, F11 and F28 genotypes were sequenced on the Illumina MiSeq platform.

Analysis of clinical and microbiological data on Acinetobacter baumannii strains assist the preauthorization of antibiotics at the patient level for an effective antibiotic stewardship program.

Drug resistant Acinetobacter baumannii (A. baumannii) poses serious treatment challenges and is on the rise worldwide. The Infectious Diseases Society of America/Society for Healthcare Epidemiology of America recommends preauthorization of antibiotics to ensure successful antibiotic stewardship programs (ASWPs).

Identification of unique essential proteins from a Mycobacterium tuberculosis F15/LAM4/KZN phage secretome library.

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis disease (TB), the leading cause of death from bacterial infection worldwide. Although treatable, the resurgence of multidrug-resistant and extensively drug-resistant TB is a major setback for the fight against TB globally. Consequently, there is an urgent need for new Mtb-derived biomarkers for use in the design of new drugs and rapid point-of-care diagnostic or prognostic tools for the management of TB transmission.

Bacterial pili, with emphasis on Mycobacterium tuberculosis curli pili: potential biomarkers for point-of care tests and therapeutics.

Context: Novel biomarkers are essential for developing rapid diagnostics and therapeutic interventions Objective: This review aimed to highlight biomarker characterisation and assessment of unique bacterial pili.

Methods: A PubMed search for bacterial pili, diagnostics, vaccine and therapeutics was performed, with emphasis on the well characterised pili.

Results: In total, 46 papers were identified and reviewed.

Mycobacterium tuberculosis strains exhibit differential and strain-specific molecular signatures in pulmonary epithelial cells.

Although pulmonary epithelial cells are integral to innate and adaptive immune responses during Mycobacterium tuberculosis infection, global transcriptomic changes in these cells remain largely unknown. Changes in gene expression induced in pulmonary epithelial cells infected with M. tuberculosis F15/LAM4/KZN, F11, F28, Beijing and Unique genotypes were investigated by RNA sequencing (RNA-Seq).

Identification of Mycobacterium tuberculosis adherence-mediating components: a review of key methods to confirm adhesin function.

Anti-adhesion therapy represents a potentially promising avenue for the treatment and prevention of tuberculosis in a post-antibiotic era. Adhesins are surface-exposed microbial structures or molecules that enable pathogenic organisms to adhere to host surfaces, a fundamental step towards host infection. Although several Mycobacterium tuberculosis adhesins have been identified, it is predicted that numerous additional adherence-mediating components contribute to the virulence and success of this pathogen.

Canonical pathways, networks and transcriptional factor regulation by clinical strains of Mycobacterium tuberculosis in pulmonary alveolar epithelial cells.

Limited knowledge exists on pathways, networks and transcriptional factors regulated within epithelial cells by diverse Mycobacterium tuberculosis genotypes. This study aimed to elucidate these mechanisms induced in A549 epithelial cells by dominant clinical strains in KwaZulu-Natal, South Africa. RNA for sequencing was extracted from epithelial cells at 48 h post-infection with 5 strains at a multiplicity of infection of approximately 10:1.

Evaluation of the role of Mycobacterium tuberculosis pili (MTP) as an adhesin, invasin, and cytokine inducer of epithelial cells.

This study was undertaken in order to assess the involvement of Mycobacterium tuberculosis pili (MTP) as an adhesin, invasin, and cytokine inducer in the M. tuberculosis-epithelial cell interaction. A MTP-deficient strain of M.

Pili of Mycobacterium tuberculosis: current knowledge and future prospects.

Many pathogenic bacteria express filamentous appendages, termed pili, on their surface. These organelles function in several important bacterial processes, including mediating bacterial interaction with, and colonization of the host, signalling events, locomotion, DNA uptake, electric conductance, and biofilm formation. In the last decade, it has been established that the tuberculosis-causing bacterium, Mycobacterium tuberculosis, produces two pili types: curli and type IV pili.

Primary Capreomycin Resistance Is Common and Associated With Early Mortality in Patients With Extensively Drug-Resistant Tuberculosis in KwaZulu-Natal, South Africa.

Background: Capreomycin is a key antimycobacterial drug in treatment of extensively drug-resistant tuberculosis (XDR-TB). Drug-susceptibility testing (DST) for capreomycin is not routinely performed in newly diagnosed XDR-TB in South Africa. We performed this study to assess the prevalence, clinical significance, and molecular epidemiology of capreomycin resistance in newly diagnosed patients with XDR-TB in KwaZulu-Natal, South Africa.

Mycobacterium tuberculosis Pili promote adhesion to and invasion of THP-1 macrophages.

Central to the paradigm of the pathogenesis of Mycobacterium tuberculosis is its ability to attach to, enter, and subsequently survive in host macrophages. However, little is known regarding the bacterial adhesins and invasins involved in this interaction with host macrophages. Pili are cell-surface structures produced by certain bacteria and have been implicated in adhesion to and invasion of phagocytes in several species.

Mycobacterium tuberculosis adhesins: potential biomarkers as anti-tuberculosis therapeutic and diagnostic targets.

Adhesion to host cells is a precursor to host colonization and evasion of the host immune response. Conversely, it triggers the induction of the immune response, a process vital to the host's defence against infection. Adhesins are microbial cell surface molecules or structures that mediate the attachment of the microbe to host cells and thus the host-pathogen interaction.