Kanzari, L. | Search bioRxiv

bioRxiv2024

Impact of methicillin resistance on virulence factor expression in 1 Staphylococcus aureus: Insights from gene expression profiling

Staphylococcus aureus is a major human pathogen causing various clinical infections and a leading cause of morbidity and mortality worldwide. S. aureus infections are problematic due to frequent antibiotic resistance, especially to methicillin. This study investigated 30 unduplicated S. aureus strains from clinical samples to establish a link between methicillin resistance and virulence factors.We detected and determined expression levels of the mecA gene, virulence genes (spdC, spA, atlA), and the RNAIII regulator using qRT-PCR. All virulence genes and the RNAIII regulator were detected in all strains. Phenotypic results showed only three strains (10%) were methicillin-resistant, while 12 (40%) carried the mecA gene. mecA-positive strains exhibited high expression of adhesion factors (spA) and biofilm formation factors (atlA), but low expression of the RNAIII regulator. The regulators expression was negatively correlated with mecA gene expression. Using a multilayer association network, we found a correlation between phenotypic methicillin resistance expression and mecA gene transcription in S. aureus mecA+. Understanding S. aureus virulence determinants will help develop anti-virulence strategies, especially given the lack of an anti-S. aureus vaccine and rising antibiotic resistance. HighlightsO_LIComplex interplay between methicillin resistance and virulence: Our study unveils a complex interplay between methicillin resistance and the expression of virulence genes in Staphylococcus aureus clinical isolates. C_LIO_LIPhenotypic and molecular correlation: Phenotypic resistance to methicillin was observed in only 10% of the isolates, whereas 40% carried the mecA gene. Molecular analysis revealed distinct expression patterns, notably elevated spA and atlA expression, in mecA+ strains. C_LIO_LINegative correlation with RNAIII: Our findings indicate a negative correlation between RNAIII regulator expression and the mecA gene in the same strains, shedding light on their regulatory relationship. C_LIO_LIMultilayer association network: Utilizing a multilayer association network, we established a correlation between phenotypic methicillin resistance and mecA gene transcription in S. aureus mecA+ strains. C_LI

microbiology↗

bioRxiv2024

Whole Genome Sequencing Analysis of a Recent Multi-Drug Resistant Shigella sonnei Outbreak Among Tunisian Children

BackgroundShigella sonnei, a leading cause of shigellosis, is a global health concern, particularly affecting children under five. The emergence of multidrug-resistant (MDR) strains, including resistance to key antibiotics like ciprofloxacin and third-generation cephalosporins, exacerbates treatment challenges. This study investigates the genetic and antimicrobial resistance profiles of S. sonnei isolates from Tunisia, focusing on an outbreak of extended-spectrum beta-lactamase (ESBL)-producing strains. MethodsWe analysed nine S. sonnei isolates collected between September 2022 and January 2023 from Tunisian hospitals, using whole genome sequencing (WGS). Standard bacterial identification and serotyping methods were employed alongside antimicrobial susceptibility testing. We examined the genetic relatedness of the isolates, identified resistance genes, and characterised virulence factors. ResultsAll the isolates were confirmed as S. sonnei H6, biotype a, and belonged to lineage 3, clade 6 and sub-lineage 3. All harboured blaCTX-M-15, conferring resistance to third-generation cephalosporins. These were chromosomally integrated, suggesting stable resistance. Five isolates exhibited fluoroquinolone resistance associated with the qnrS1 gene, and all isolates had a single quinolone resistance-determining region mutation (GyrA-D87Y). Additionally, the plasmid-borne mphA gene, conferring resistance to macrolides, was prevalent. Single-linkage hierarchical clustering analysis indicated close genetic relationships with S. sonnei strains from Europe, particularly France and the UK (0 to 31 core genome MLST allele differences), indicating recent international dissemination. ConclusionThis study provides the first comprehensive molecular characterisation of MDR S. sonnei in Tunisia, highlighting a significant public health threat. The findings underscore the importance of continuous genomic surveillance to track the spread of resistant strains and inform public health interventions.

genomics↗