An elevated level of interleukin-17A in a Senegalese malaria cohort is associated with rs8193038 IL-17A genetic variant.

Malaria infection is a multifactorial disease partly modulated by host immuno-genetic factors. Recent evidence has demonstrated the importance of Interleukin-17 family proinflammatory cytokines and their genetic variants in host immunity. However, limited knowledge exists about their role in parasitic infections such as malaria. We aimed to investigate IL-17A serum levels in patients with severe and uncomplicated malaria and gene polymorphism's influence on the IL-17A serum levels. In this research, 125 severe (SM) and uncomplicated (UM) malaria patients and 48 free malaria controls were enrolled. IL-17A serum levels were measured with ELISA. PCR and DNA sequencing were used to assess host genetic polymorphisms in IL-17A. We performed a multivariate regression to estimate the impact of human IL-17A variants on IL-17A serum levels and malaria outcomes. Elevated serum IL-17A levels accompanied by increased parasitemia were found in SM patients compared to UM and controls (P < 0.0001). Also, the IL-17A levels were lower in SM patients who were deceased than in those who survived. In addition, the minor allele frequencies (MAF) of two IL-17A polymorphisms (rs3819024 and rs3748067) were more prevalent in SM patients than UM patients, indicating an essential role in SM. Interestingly, the heterozygous rs8193038 AG genotype was significantly associated with higher levels of IL-17A than the homozygous wild type (AA). According to our results, it can be concluded that the IL-17A gene rs8193038 polymorphism significantly affects IL-17A gene expression. Our results fill a gap in the implication of IL-17A gene polymorphisms on the cytokine level in a malaria cohort. IL-17A gene polymorphisms also may influence cytokine production in response to Plasmodium infections and may contribute to the hyperinflammatory responses during severe malaria outcomes.

Detection of Hepatitis E Virus (HEV) in Pork Sold in Saint-Louis, the North of Senegal.

The hepatitis E virus (HEV) is a zoonotic pathogen with various hosts, including pigs, which act as reservoirs. In industrialized countries, sporadic cases caused by genotype 3, contracted by ingesting contaminated uncooked or undercooked meat, have been reported. However, in developing countries, HEV infection is mainly dominated by genotype 2 and often associated with poor hygiene conditions and drinking water supplies. HEV infection and its circulation in domestic fauna in West Africa are poorly documented. This study aimed to assess the presence of HEV in pork sold in Saint-Louis, Senegal. Meat products (250 g samples, n = 74) were purchased in August 2022 from three locations. Then, 2 g/sample was minced to extract total nucleic acids using the Purelink™ Viral DNA/RNA kit. RT-PCR reactions were performed using the One-Taq™ One-Step RT-PCR kit targeting the HEV ORF2 genomic region. The products obtained were visualized on a 1% agarose gel. Of a total of 74 samples, divided into pork meat (n = 65) and pork liver (n = 9), 5.4% (n = 4) tested positive for HEV. In both cases, two samples were positive, representing a rate of 3.1% and 22.2% for meat and pork liver, respectively. All new viral sequences were obtained from a monophyletic group within HEV genotype 3. This study is the first to report the presence of HEV in pork sold in Senegal and the results reveal a potential circulation of HEV in the pig population. The high proportion of contamination in the pork liver samples highlights a major risk associated with their consumption.

A metagenomic assessment of bacterial community in spices sold open-air markets in Saint-Louis, Senegal.

Natural spices play an essential role in human nutrition and well-being. However, their processing on different scales can expose them to potential sources of contamination. This study aimed to describe the bacterial community genomic footprint in spices sold in Senegal. Spice samples were collected in August 2022 in Saint-Louis, Senegal. The genomic region coding bacterial 16S rRNA was then amplified and sequenced using Oxford Nanopore Technology (ONT). Sequencing was carried out on two batches of samples, one containing part of the "Local Spices or Herbs" (n = 10), and the other, a mixture of 7 spices, Curcuma, Thyme and the other part of the "Local Spices or Herbs" (n = 39). Results showed high bacterial diversity and the predominance of Escherichia coli and Salmonella enterica in samples, with total reads of 65,744 and 165,325 for the two batches, respectively. The sample category "Homemade mixture of food condiments ", which includes all "Local Spices or Herbs" samples, showed remarkable bacterial diversity. These were followed by Curcuma, a blend of 7 spices and thyme. Also, the different categories of spices studied show similarities in their bacterial composition. These results highlight the microbial community's highly diverse genomic profile, including pathogenic bacteria, in spice samples.

Rational antibiotic design: in silico structural comparison of the functional cavities of penicillin-binding proteins and ß-lactamases.

The class of ß-lactam antibiotics has proven highly efficient in targeting bacterial penicillin-binding proteins (PBP) leading to the blocking of the bacterial cell wall synthesis. However, the benefit of these drugs is limited because of bacterial resistance mechanisms; the most widespread resistance involves ß-lactamase enzymes (ßLACT) that inactivate ß-lactam-based molecules. We focused on PBPs and ßLACTs from enterobacteria, and performed a detailed in silico study of PBPs whose inactivation is lethal for the bacteria and of ßLACTs that have a PBP-type catalytic mechanism. The comparison of the sequences and structures of PBPs and ßLACTs shows an almost perfect conservation of the catalytic site, and a high spatial resemblance of the whole functional cavity despite a very low overall sequence identity. Some notable differences in the functional cavity were observed in the vicinity of the catalytic site: four tyrosines are well conserved in the PBPs, whereas the residues occurring at equivalent positions in the ßLACT families present other physicochemical properties. These tyrosines are thus good candidates to be targeted in designing new antibiotic molecules with increased affinity and specificity for PBPs, with the goal of overcoming drug resistance. Our analysis also identified residues that have similar characteristics in most ßLACT families and different properties in PBPs; these are interesting targets for new ligands that specifically inhibit ßLACT proteins. The in silico approach presented here can be extended to other protein systems in view of guiding and improving rational drug design.

A comprehensive computational study of amino acid interactions in membrane proteins.

Transmembrane proteins play a fundamental role in a wide series of biological processes but, despite their importance, they are less studied than globular proteins, essentially because their embedding in lipid membranes hampers their experimental characterization. In this paper, we improved our understanding of their structural stability through the development of new knowledge-based energy functions describing amino acid pair interactions that prevail in the transmembrane and extramembrane regions of membrane proteins. The comparison of these potentials and those derived from globular proteins yields an objective view of the relative strength of amino acid interactions in the different protein environments, and their role in protein stabilization. Separate potentials were also derived from α-helical and ß-barrel transmembrane regions to investigate possible dissimilarities. We found that, in extramembrane regions, hydrophobic residues are less frequent but interactions between aromatic and aliphatic amino acids as well as aromatic-sulfur interactions contribute more to stability. In transmembrane regions, polar residues are less abundant but interactions between residues of equal or opposite charges or non-charged polar residues as well as anion-π interactions appear stronger. This shows indirectly the preference of the water and lipid molecules to interact with polar and hydrophobic residues, respectively. We applied these new energy functions to predict whether a residue is located in the trans- or extramembrane region, and obtained an AUC score of 83% in cross validation, which demonstrates their accuracy. As their application is, moreover, extremely fast, they are optimal instruments for membrane protein design and large-scale investigations of membrane protein stability.