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Biology subjects

Ivan, M.

Publications and source records attributed to Ivan, M..

3 recordsLinked to original sources

Incremental AMR acquisition driving successive genotype replacements and the rise of extensively drug resistant (XDR) Shigella sonnei in Australia over 20 years.

BackgroundIn Australia, the burden of shigellosis is predominantly in returning travellers or in men who have sex with men (MSM). Here, we combine genomic data with comprehensive epidemiological data on sexual exposure and international travel to explore population dynamics of Shigella sonnei and the expansion of multi-drug resistant (MDR) and extensively drug-resistant (XDR) sub-lineages. MethodsA population-level study of all cultured Shigella sonnei isolates in the state of Victoria, Australia, was undertaken between January 2002 and December 2024. Antimicrobial susceptibility testing, whole-genome sequencing, and bioinformatic analyses of 1,305 Shigella sonnei isolates were performed at the Microbiological Diagnostic Unit Public Health Laboratory. Enhanced metadata on source attribution including travel and sexual exposure were collected through surveillance forms or by interviews. ResultsThis study highlights significant shifts in Shigella sonnei cases in Victoria from sensitive strains to MDR and then XDR, particularly in the MSM-associated groups but also associated with a large point source outbreak. We describe an historical pattern of shifting genotype prevalence, and replacement to more varied and higher proportions of antimicrobial resistance over the last decade, resulting in the establishment of two distinct but highly concerning XDR sub-lineages within Victoria. ConclusionsOur genomic-epidemiological analyses highlight that drug-resistant Shigella sonnei remains an ongoing public health threat, and the importance of ongoing surveillance. We determined local evolutionary trajectories and identified expanding sub-lineages that informed shifts in clinical management and antimicrobial recommendations over time, including the use of azithromycin and carbapenems. Placing these local dynamics within the broader global epidemiology, we link how regional evolution interconnects with international dissemination, proving valuable context for guiding local, national and global strategies for prevent outbreaks and antimicrobial resistance.

microbiology↗

miR-210 locus deletion disrupts cellular homeostasis; an integrated genetic study

MiR-210 is widely recognized as the quintessential hypoxia-responsive miRNA and thought to fine-tune various facets of cellular homeostasis. We hereby present an integrative appraisal of phenotypic and molecular repercussions of disrupting the corresponding locus in human and mouse cells using multiple genetic strategies. Briefly, MIR210 deletion led to decreased cellular fitness and suboptimal responses to several stress types. Transcriptomic comparisons using different profiling platforms, performed independently by members of this collaboration, revealed consistent deregulation of neighboring genes, in locus-disrupted cells. Interestingly, the anticipated enrichment in miR-210 targets failed to materialize in unbiased analyses. Our results point to the biological significance of unrecognized regulatory elements that overlap miRNA genes and should serve as note of caution for studies based for genetic disruption of such loci.

molecular biology↗

miR-210 is essential to retinal homeostasis in fruit flies and mice

miR-210 is one of the most evolutionarily conserved microRNAs. Recent studies in Drosophila melanogaster have unveiled that the absence of miR-210 leads to a progressive retinal degeneration characterized by the accumulation of lipid droplets and disruptions in lipid metabolism. Further investigation into lipid anabolism and catabolism revealed significant alterations in gene expression within these pathways. We provide the first morphological characterization of miR-210 KO mice retinas, highlighting a significant photoreceptor degeneration. While exploring potential parallels between miR-210 KO models in flies and mice, we examined mice lipid metabolism, circadian behaviour, and retinal transcriptome yet found no resemblances, suggesting divergent mechanisms of retinal degeneration between the two species. Simultaneously, analysis of the transcriptome in the brains of miR-210 KO flies revealed the potential existence of a shared upstream mechanism contributing to retinal degeneration in both fruit flies and mammals.

genetics↗