Biology subjects

Valcanis, M.

Publications and source records attributed to Valcanis, M..

4 recordsLinked to original sources

bioRxiv2024

Dynamics of antimicrobial resistance and virulence of Salmonella enterica serovar Dublin

Salmonella Dublin is a host-adapted, invasive non-typhoidal Salmonella (iNTS) serovar that causes bloodstream infections in humans and demonstrates increasing prevalence of antimicrobial resistance (AMR). Using a global dataset of 1,303 genomes, coupled with in vitro assays, we examined the evolutionary, resistance, and virulence characteristics of S. Dublin. Our analysis revealed strong geographic associations between AMR profiles and plasmid types, with highly resistant isolates confined predominantly to North America, linked to IncC plasmids co-encoding AMR and heavy metal resistance. By contrast, Australian isolates were largely antimicrobial-susceptible, reflecting differing AMR pressures. We identified two phylogenetically distinct Australian lineages, ST10 and ST74, with a small number of ST10 isolates harbouring a novel hybrid plasmid encoding both AMR and mercuric resistance. Whereas the ST10 lineage remains globally dominant, the ST74 lineage was less prevalent. ST74 exhibited unique genomic features including a larger pan genome compared to ST10 and the absence of key virulence loci including SPI-19 which encodes a type VI secretion system (T6SS). Despite these genomic differences, the ST74 lineage displayed enhanced intracellular replication in human macrophages and induced less pro-inflammatory responses compared with ST10, suggesting alternative virulence strategies that may support systemic dissemination of ST74. The Vi antigen was absent in all ST10 and ST74 genomes, highlighting challenges for serotyping and vaccine development, and has implications for current diagnostic and control strategies for S. Dublin infections. Collectively, this study represents the most comprehensive investigation of S. Dublin to date and importantly, has revealed distinct adaptations of two genotypes within the same serovar, leading to different epidemiological success. The regional emergence and evolution of distinct S. Dublin lineages highlights the need to understand the divergence of intra-serovar virulence mechanisms which may impact the development of effective control measures against this important global pathogen.

microbiology↗

bioRxiv2024

Genomic epidemiology and phenotypic characterisation of Salmonella entericaserovar Panama in Victoria, Australia

Salmonella enterica serovar Panama, a causative agent of non-typhoidal salmonellosis (NTS), is one of several serovars that causes invasive NTS disease (iNTS) in humans. S. Panama is an understudied pathogen, with its pathobiology poorly understood. It is a predominant iNTS serovar in Australia, a high-income country with high rates of salmonellosis, where S. Panama has been documented to have a high odds ratio for causing iNTS. This study investigates the genomic epidemiology and antimicrobial resistance profiles of all S. Panama isolates recovered in Victoria, Australia, between 2000 and 2020. We examined the infection dynamics of S. Panama in seven isolates, representing the genetic diversity of the study population. Two sub-lineages, encompassed within a previously described Asian lineage, were identified. Multi-drug resistance (resistance to [≥]3 drug classes) was detected in 46 (51.7%) Australian isolates. The plasmid-mediated colistin resistance gene, mcr1.1, was detected in one Australian S. Panama isolate, carried by an IncI plasmid previously reported in Salmonella and Escherichia coli isolates collected from poultry in South-East Asia. Examination of the intracellular replication dynamics of S. Panama isolates demonstrated diverse phenotypes. In THP-1 derived macrophages, despite low host cell uptake, S. Panama showed higher replication rates over time compared to S. enterica serovar Typhimurium. However, a causative genotype could not be identified to explain this observed phenotype. This study provides insights into the S. Panama isolates imported into Australia over two-decades, showing MDR was common in this iNTS serovar, and colistin resistance reported for the first time. It provides the first data on the host-pathogen interactions of S. Panama in Australia, which will aid our collective understanding of the pathobiology of S. Panama and iNTS serovars more broadly. Author SummaryIn Australia, non-typhoidal Salmonella (NTS) cases have been on the rise since the 1970s; characterised by self-limiting enteritis, some NTS infections can result in systemic infections called invasive NTS disease. Salmonella enterica serovar Panama is a leading iNTS serovar in Australia. This study characterised the genomic epidemiology of S. Panama, identifying two lineages circulating in Australia over two decades and placing them within a global context. It also investigated the antimicrobial resistance (AMR) mechanisms of S. Panama, with multi-drug resistance commonly observed. Further, it identified the first plasmid-mediated colistin-resistant S. Panama in Australia. We additionally examined the characteristics of S. Panama-mediated host-pathogen interactions in both epithelial and macrophage cells lines, providing the first insight into the infection dynamics of this understudied pathogen. Thus, this study combines genomics and in vitro infection experiments to understand the pathogenic behaviour of the neglected iNTS S. Panama.

microbiology↗

bioRxiv2023

Genetic heterogeneity in the Salmonella Typhi Vi capsule locus: A population genomic study from Fiji

Typhoid fever is endemic in many parts of the world and remains a major public health concern in tropical and sub-tropical developing nations, including Fiji. To address high rates of typhoid fever, the Northern Division of Fiji is implementing a mass vaccination with typhoid conjugate vaccine (Vi-polysaccharide conjugated to tetanus toxoid) as a public health control measure in 2023. In this study we define the genomic epidemiology of S. Typhi in the Northern Division prior to island-wide vaccination, sequencing 85% (n=419) of the total cases from the Northern Division and Central Divisions of Fiji that occurred in the period 2017-2019. We found elevated rates of nucleotide polymorphisms in tviD and tviE genes (responsible for Vi-polysaccharide synthesis) relative to core genome levels within the Fiji endemic S. Typhi genotype 4.2. Expansion of these findings within a globally representative database of 12,382 S. Typhi (86 genotyphi clusters) showed evidence of convergent evolution of the same tviE mutations across the S. Typhi population, indicating that tvi selection has occurred both independently and globally. The functional impact of tvi mutations on the Vi-capsular structure and other phenotypic characteristics are presently unknown, yet commonly occurring tviE polymorphisms localise adjacent to predicted active site residues when overlayed against the predicted TviE protein structure. Given the central role of the Vi-polysaccharide in S. Typhi biology and vaccination, further integrated epidemiological, genomic, and phenotypic surveillance is required to determine the spread and functional implications of these mutations.

microbiology↗

bioRxiv2022

Bridging the gap between bioinformatics and the clinical and public health microbiology laboratory: An ISO-accredited genomics workflow for antimicrobial resistance

Realising the promise of genomics to revolutionise routine AMR diagnosis and surveillance has been a long-standing challenge in clinical and public health microbiology. We have directly addressed this issue by creating and validating abritAMR, an ISO-accredited bioinformatics platform for genomics-based bacterial AMR gene detection. abritAMR utilises the NCBI AMRFinderPlus for detection of AMR genes and mutations, with additional features to classify AMR determinants into an antibiotic class. We validated abritAMR by comparing with multiplex PCR or gold-standard reference genomes, together representing 1500 different bacteria across 29 genera and covering 415 antibiotic resistance alleles. We also assessed inference of phenotypic resistance by comparing genomic predictions with agar dilution results for 864 Salmonella spp. Performance of abritAMR was excellent, detecting AMR genes with 99.9% accuracy (95% CI 99.9-99.9%), 97.9% sensitivity (95% CI 97.5-98.4%) and 100% specificity (100-100%). Phenotypic inference of resistance for Salmonella spp. was equally impressive, with 98.9% accuracy (98.7-99.1%). Validation data were submitted to the governing authority and ISO15189 accreditation was achieved. Implementation of abritAMR resulted in streamlined bioinformatics and reporting pathways, and it was readily updated and re-verified with database revisions or changes in reporting requirements. abritAMR is publicly and freely available to assist clinical and public health microbiology laboratories everywhere harness the power of AMR genomics in their professional practice.

microbiology↗