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Background Chlamydiae are intracellular bacteria that cause various severe diseases in humans and animals. The common treatment for chlamydia infections are antibiotics. However, when antibiotics are misused (overuse or self-medication), this may lead to resistance of a number of chlamydia species, causing a real public health problem worldwide. Materials and methods In the present work, a comprehensive literature search was conducted in the following databases: PubMed, Google Scholar, Cochrane Library, Science direct and Web of Science. The primary purpose is to analyse a set of data describing the genes and mutations involved in Chlamydiae resistance to antibiotic mechanisms. In addition, we proceeded to a filtration process among 704 retrieved articles, then finished by focusing on 24 studies to extract data that met our requirements. Results The present study revealed that Chlamydia trachomatis may develop resistance to macrolides via mutations in the 23S rRNA , rplD , rplV genes, to rifamycins via mutations in the rpoB gene, to fluoroquinolones via mutations in the gyrA , parC and ygeD genes, to tetracyclines via mutations in the rpoB gene, to fosfomycin via mutations in the murA gene, to MDQA via mutations in the secY gene. Whereas, Chlamydia pneumoniae may develop resistance to rifamycins via mutations in the rpoB gene, to fluoroquinolones via mutations in the gyrA gene. Furthermore, the extracted data revealed that Chlamydia psittaci may develop resistance to aminoglycosides via mutations in the 16S rRNA and rpoB genes, to macrolides via mutations in the 23S rRNA gene. Moreover, Chlamydia suis can become resistance to tetracyclines via mutations in the tet(C) gene . In addition, Chlamydia caviae may develop resistance to macrolides via variations in the 23S rRNA gene. The associated mechanisms of resistance are generally: the inhibition of bacteria’s protein synthesis, the inhibition of bacterial enzymes’ action and the inhibition of bacterial transcription process. Conclusion This literature review revealed the existence of diverse mutations associated with resistance to antibiotics using molecular tools and targeting chlamydia species’ genes. Furthermore, these mutations were shown to be associated with different mechanisms that led to resistance. In that regards, more mutations and information can be shown by a deep investigation using the whole genome sequencing. Certainly, this can help improving to handle chlamydia infections and healthcare improvement by decreasing diseases complications and medical costs.

Background Antibiotics are frequently used to treat infections caused by Chlamydia pneumoniae ; an obligate intracellular gram-negative bacterium commonly associated with respiratory diseases. However, improper or overuse of these drugs has raised concerns about the development of antibiotic resistance, which poses a significant global health challenge. Previous studies have revealed a link between mutations in the rpoB -encoded protein of C. pneumoniae and antibiotic resistance. This study assessed these mutations via various bioinformatics tools to predict their impact on function, structural stability, antibiotic binding, and, ultimately, their effect on bacterial sensitivity to antibiotics. Results Eight mutations in the rpoB -encoded protein (R421S, F450S, L456I, S454F, D461E, S476F, L478S, and S519Y) are associated with resistance to rifampin and rifalazil. These mutations occur in conserved regions of the protein, leading to decreased stability and affecting essential functional sites of RNA polymerase, the target of these antibiotics. Although the structural differences between the native and mutant proteins are minimal, notable changes in local hydrogen bonding have been observed. Despite similar binding energies, variations in hydrogen bonds and hydrophobic interactions in certain mutants (for instance, D461E for rifalazil and S476F for rifampin) indicate that these changes may diminish ligand affinity and specificity. Furthermore, protein-protein network analysis demonstrated a strong correlation between wild-type rpoB and ten C. pneumoniae proteins, each fulfilling specific functional roles. Consequently, some of these mutations can reduce the bacterium’s sensitivity to rifampin and rifalazil, thereby contributing to antibiotic resistance. Conclusion The findings of this study indicate that mutations in the rpoB gene, which encodes the beta subunit of RNA polymerase, are pivotal in the resistance of C. pneumoniae to rifampin and rifalazil. Some of these mutations may result in reduced protein stability and changes in the structure, function, and antibiotic binding. As a consequence, the efficacy of these drugs in inhibiting RNA polymerase is compromised, allowing the bacteria to persist in transcription and replication even in the presence of antibiotics. Overall, these insights enhance our understanding of the resistance mechanisms in C. pneumoniae and could guide the development of strategies to address this challenge. Clinical trial number Not applicable.

Chlamydia trachomatis is an obligate intracellular gram-negative pathogen, responsible for diverse affections, mainly trachoma and sexually transmitted diseases. Antibiotics are the commonly used drugs to tackle chlamydiae infections. However, when overused or wrongly used this may lead to strains' resistance to antibiotics, this phenomenon represents a real health problem worldwide. Numerous studies showed the association of Chlamydia trachomatis resistance with mutations in different genes; these mutations could have a deleterious or neutral impacts on the encoded proteins. The aim of this study is to perform an in silico analysis of C. trachomatis rpoB-encoded proteins using numerous bioinformatics tools and to identify the functional and structural-related effects of the mutations and consequently their impact on the bacteria sensitivity to antibiotics. The analysis revealed that the prediction of the damaging impact related to the mutations in rpoB-encoded proteins showed eight mutations: V136F, Q458K, V466A, A467T, H471N, H471Y, H471L, and I517M with big deleterious effects. Among them, six mutations, V136F, Q458K, V466A, A467T, H471N, and I517M, are located in a highly conserved regions decreasing the protein's stability. Furthermore, the structures analysis showed that the mutations A467T, H471N, I517M, and V136F models had a high deviation compared to the wild type. Moreover, the prediction of protein-protein network indicated that rpoB wild type interacts strongly with 10 proteins of C. trachomatis, which are playing different roles at different levels. As conclusion, the present study revealed that the changes observed in the encoded proteins can affect their functions and structures, in addition to their interactions with other proteins which impact the bacteria sensitivity to antibiotics. Consequently, the information revealed through this in silico analysis would be useful for deeper exploration to understand the mechanisms of C. trachomatis resistance and enable managing the infection to avoid its complications. We recommend further investigations and perform deeper experimental analysis with collaboration between bioinformaticians, physicians, biologists, pharmacists, and chemistry and biochemistry scientists.

Background Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer, characterized by distinct clinicopathological features and a relatively high frequency in North African countries. While several studies have explored the genetic basis of breast cancer, limited research has looked into the specific genetic features of this aggressive form. This study aims to investigate the genetic factors associated with IBC in North Africa, particularly among Tunisian patients. Methods Whole exome sequencing was performed for 13 patients with IBC. Clinicopathological data have been collected to assess the phenotype-genotype correlation. Both germline point mutations and copy number variations (CNVs) were analyzed. Genes and variants were prioritized through phenotype and genotype-driven approaches. Variants were filtered based on pathogenicity predictions and ACMG classification. A Gene-Disease association analysis was conducted using DisGeNET data and the VarElect online tool to select candidate genes most likely involved in disease onset. The predictive and prognostic values of the relevant genes were assessed using publicly available datasets. Results Our investigations revealed relevant genetic variants within established cancer predisposing genes, inflammatory pathways, and potential candidate predisposing genes, including BRCA2 c.1794_1798del, a novel mutation in RAD54L gene (c.1712T > C) and c.555_559del in IFNAR2 gene. CNVs in ABRAXAS1, XRCC2 and FANC genes were identified. We have also found that the high expression levels of RAD54L and MTHFR are correlated with good survival rates. The genetic makeup of IBC seems to be very heterogeneous. For the same patient, we have detected several relevant variants that might explain disease development and progression, and this was consistent with the family history of cancer observed in the investigated families. Conclusions Our findings revealed a complex and heterogeneous genetic background of IBC in the Tunisian population that might contribute to disease susceptibility and impact disease prognosis. The genetic features of IBC presented in this study provide valuable insights into the molecular mechanisms underlying the disease offering not only a deeper understanding within the context of Tunisia but also shedding light on its relevance to other North African populations characterized by similar epidemiological and genetic features.

Modern biomedical research is characterised by its high-throughput and interdisciplinary nature. Multiproject and consortium-based collaborations requiring meaningful analysis of multiple heterogeneous phenotypic datasets have become the norm; however, such analysis remains a challenge in many regions across the world. An increasing number of data harmonisation efforts are being undertaken by multistudy collaborations through either prospective standardised phenotype data collection or retrospective phenotype harmonisation. In this regard, the Phenotype Harmonisation Working Group (PHWG) of the Human Heredity and Health in Africa (H3Africa) consortium aimed to facilitate phenotype standardisation by both promoting the use of existing data collection standards (hosted by PhenX), adapting existing data collection standards for appropriate use in low- and middle-income regions such as Africa, and developing novel data collection standards where relevant gaps were identified. Ultimately, the PHWG produced 11 data collection kits, consisting of 82 protocols, 38 of which were existing protocols, 17 were adapted, and 27 were novel protocols. The data collection kits will facilitate phenotype standardisation and harmonisation not only in Africa but also across the larger research community. In addition, the PHWG aims to feed back adapted and novel protocols to existing reference platforms such as PhenX.

Effective interventions and treatments for complex diseases have been implemented globally, however, coverage in Africa has been comparatively lower due to lack of capacity, clinical applicability and knowledge on the genetic contribution to disease and treatment. Currently, there is a scarcity of genetic data on African populations, which have enormous genetic diversity. Pharmacogenomics studies have the potential to revolutionise treatment of diseases, therefore, African populations are likely to benefit from these approaches to identify likely responders, reduce adverse side effects and optimise drug dosing. This review discusses clinical pharmacogenetics studies conducted in African populations, focusing on studies that examined drug response in complex diseases relevant to healthcare. Several pharmacogenetics associations have emerged from African studies, as have gaps in knowledge.

Chlamydia pneumoniae is a respiratory pathogen associated with chronic inflammatory diseases such as asthma and atherosclerosis, and its detection in human carotid and coronary atheroma suggests some support for its involvement in atherogenesis. The main objective of our study was to evaluate the association between Chlamydia pneumoniae and atherosclerosis in Moroccan patients through a case-control approach and detected strain genotyping. A total of 137 cases and 124 controls were enrolled, nested PCR was performed for Chlamydia pneumoniae screening of the peripheral blood mononuclear cells (PBMCs) of both cases and controls as well as atheroma plaques from 37 cases, and positive samples were subjected to sequencing for genotyping and phylogenetic analysis. The results showed 54% and 18%, respectively, for positivity in cases and control PBMCs and 86.5% in atheroma plaques, the difference being significant between the two groups (P < 0.001, ORa = 8.580, CI, 95% [3.273-22.491]). Strain sequence analyses showed more than 98% similarity with human reference strains, and revealed various genotypes. This study supports the involvement of Chlamydia pneumoniae in atherosclerosis in the studied population and genotyping revealed that detected strains were identical to human strains circulating worldwide.

Genomics data are currently being produced at unprecedented rates, resulting in increased knowledge discovery and submission to public data repositories. Despite these advances, genomic information on African-ancestry populations remains significantly low compared with European- and Asian-ancestry populations. This information is typically segmented across several different biomedical data repositories, which often lack sufficient fine-grained structure and annotation to account for the diversity of African populations, leading to many challenges related to the retrieval, representation and findability of such information. To overcome these challenges, we developed the African Genomic Medicine Portal (AGMP), a database that contains metadata on genomic medicine studies conducted on African-ancestry populations. The metadata is curated from two public databases related to genomic medicine, PharmGKB and DisGeNET. The metadata retrieved from these source databases were limited to genomic variants that were associated with disease aetiology or treatment in the context of African-ancestry populations. Over 2000 variants relevant to populations of African ancestry were retrieved. Subsequently, domain experts curated and annotated additional information associated with the studies that reported the variants, including geographical origin, ethnolinguistic group, level of association significance and other relevant study information, such as study design and sample size, where available. The AGMP functions as a dedicated resource through which to access African-specific information on genomics as applied to health research, through querying variants, genes, diseases and drugs. The portal and its corresponding technical documentation, implementation code and content are publicly available.