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Abstract: Resistance to fusidic acid in Staphylococcus aureus is caused by mutation of the elongation factor G (EF-G) encoded by fusA or by expression of a protein, encoded by fusB or fusC, that protects the drug target. Other mechanisms involved in this resistance are mutations in the riboprotein L6 operon within rplF. The aim of this study was to determine the prevalence and mechanisms of resistance to fusidic acid in clinical isolates of S. aureus in Casablanca (Morocco) and to define the phenotypic and genotypic traits of these isolates and their clonal relationship. All fusidic acid-resistant S. aureus (FAR-SA) isolates were tested for fusB and fusC genes and were evaluated for the detection of mutations in fusA and fusE (rplF). fusB-positive strains were tested for a cadDX operon, encoding cadmium resistance. The agr group and the presence of toxin genes were monitored to characterize all FAR-SA isolates which were typed by pulsed-field gel electrophoresis (PFGE) and spa typing. Among 140 clinical S. aureus isolates collected in 2007 and 2008, 18 (∼13%) exhibited resistance to fusidic acid. The most common resistance determinant was fusC, found in 16 isolates. Molecular typing showed that 14 of them harboured an agr group III and belonged to the same clonal complex (CC) spa type 127 and identical clonotype (cluster labelled A). These isolates also possessed the staphylococcal enterotoxin H gene. The second resistance determinant was fusB found in two isolates. These two isolates lacked cadDX gene and were found to belong to two unrelated clusters and spa types. While no isolate carrying mutations in rplF was found, 15 expressed a silent mutation in fusA (nucleotide 342). Only acquired fusidic acid resistance genes (mainly fusC) were prevalent among FAR-SA isolates with almost all of the clinical specimens belonging to CC-spa type 127. This study provides valuable data on the prevalence of fusidic acid-resistant S. aureus with the associated molecular mechanisms of resistance and the genetic background of the strains in Casablanca. [Copyright &y& Elsevier]

In Marseille, France, the COVID-19 incidence evolved unusually with several successive epidemic phases. The second outbreak started in July, was associated with North Africa, and involved travelers and an outbreak on passenger ships. This suggested the involvement of a new viral variant. We sequenced the genomes from 916 SARS-CoV-2 strains from COVID-19 patients in our institute. The patients' demographic and clinical features were compared according to the infecting viral variant. From June 26th to August 14th, we identified a new viral variant (Marseille-1). Based on genome sequences (n = 89) or specific qPCR (n = 53), 142 patients infected with this variant were detected. It is characterized by a combination of 10 mutations located in the nsp2 , nsp3 , nsp12 , S , ORF3a, ORF8 and N/ORF14 genes. We identified Senegal and Gambia, where the virus had been transferred from China and Europe in February–April as the sources of the Marseille-1 variant, which then most likely reached Marseille through Maghreb when French borders reopened. In France, this variant apparently remained almost limited to Marseille. In addition, it was significantly associated with a milder disease compared to clade 20A ancestor strains, in univariate analysis. Our results demonstrate that SARS-CoV-2 can genetically diversify rapidly, its variants can diffuse internationally and cause successive outbreaks. [ABSTRACT FROM AUTHOR]

Abstract Background & aims Chronic Hepatitis C is one of the most important risk factors of liver cirrhosis and hepatocellular carcinoma. Before reaching these ultimate steps, insulin resistance triggered by hepatitis C virus infection is known to participate in the progression of liver disease. The present study aims to investigate the influence of two functional polymorphisms on SOCS3 mRNA expression and on the outcomes of CHC progression in a North African context. Patients & methods In this case-control study, 601 Moroccan subjects composed of 200 healthy controls, 101 resolvers and 300 patients with persistent HCV infection including 95 mild chronic hepatitis, 131 Advanced Liver Diseases and 74 HCC were enrolled. They were genotyped for the 4874 A/G (rs4969170) and A + 930– > G (rs4969168) SOCS3 variants using TaqMan SNPs assays. SOCS3 mRNA expression was assessed using Real Time PCR technique. Results Logistic regression analysis showed that variation at rs4969168 was associated with spontaneous clearance of HCV (P < 0.05). In addition, minor allele frequencies were significantly higher in AdLD patients when compared to the mCHC group both for rs4969168 (P = 7.0 E-04) and rs4969170 (P = 4.0 E-05). A significant association between haplotype and liver disease progression was also found. Moreover, SOCS3 mRNA was significantly more expressed in peripheral leukocytes from patients with HCC than in those from mCHC. Finally, rs4969170 was significantly associated with LDL-lipoprotein (P = 0.04), total cholesterol (P = 5.0 E-04), and higher fasting glucose levels (P = 0.005) in patients with persistent HCV infection. Conclusions Our results underline the importance of the functional SOCS3 polymorphisms in the modulation of CHC progression and suggest their contribution to HCC development by affecting its mRNA expression and perturbing key metabolic parameters. Highlights • The SOCS3 polymorphisms may modulate the progression of HCV infection to advanced liver disease. • rs4969170-A allele at SOCS3 perturbs key metabolic parameters in Moroccan patients with chronic hepatitis C. • rs4969170-A allele at SOCS3 promoter region increases SOCS3 mRNA expression. • The SOCS3 polymorphism modulates HCC development by affecting mRNA expression. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Paraoxonase 1 (PON1) is mainly complexed to HDL and is responsible, at least in part, for their antioxidant properties. The aims of our study were to determine the phenotype distribution and enzymatic activities of PON1 and the oxidative stress status of healthy subjects and diabetic and hemodialysis patients. Design and methods: PON1 paraoxonase and arylesterase activities and oxidative stress markers [malondialdehyde (MDA) and vitamin E levels] were measured in 300 individuals as a function of health status. Results: The prevalence of the PON1 phenotypes in the study population was 74.51%, 18.15% and 7.34% for QQ, QR and RR, respectively. The phenotype distribution did not change significantly as a function of health status (healthy, diabetes, hemodialysis). However, the hemodialysis patients had lower PON1 paraoxonase and arylesterase activities than the diabetic patients and healthy subjects, while there were no significant differences between the diabetic patients and the healthy subjects. Oxidative stress markers (MDA levels and vitamin E/cholesterol ratio) were significantly higher in the diabetic and hemodialysis patients than in the healthy subjects. Conclusions: The lower plasma PON1 enzymatic activities in the hemodialysis patients was not associated with a difference in the phenotype distribution of PON1. Oxidative stress conditions were significantly higher in these patients, which may increase the risk of atherosclerosis in this population. [Copyright &y& Elsevier]