Genomic epidemiology offers high resolution estimates of serial intervals for COVID-19.

Serial intervals - the time between symptom onset in infector and infectee - are a fundamental quantity in infectious disease control. However, their estimation requires knowledge of individuals' exposures, typically obtained through resource-intensive contact tracing efforts. We introduce an alternate framework using virus sequences to inform who infected whom and thereby estimate serial intervals.

Reversible vancomycin susceptibility within emerging ST1421 Enterococcus faecium strains is associated with rearranged vanA-gene clusters and increased vanA plasmid copy number.

Vancomycin variable enterococci (VVE) are van-positive enterococci with a vancomycin-susceptible phenotype (VVE-S) that can convert to a resistant phenotype (VVE-R) and be selected for during vancomycin exposure. VVE-R outbreaks have been reported in Canada and Scandinavian countries. The aim of this study was to examine the presence of VVE in whole genome sequenced (WGS) Australian bacteremia Enterococcus faecium (Efm) isolates collected through the Australian Group on Antimicrobial resistance (AGAR) network.

Cov2clusters: genomic clustering of SARS-CoV-2 sequences.

Background: The COVID-19 pandemic remains a global public health concern. Advances in sequencing technologies has allowed for high numbers of SARS-CoV-2 whole genome sequence (WGS) data and rapid sharing of sequences through global repositories to enable almost real-time genomic analysis of the pathogen. WGS data has been used previously to group genetically similar viral pathogens to reveal evidence of transmission, including methods that identify distinct clusters on a phylogenetic tree.

Proficiency testing for SARS-CoV-2 whole genome sequencing.

Extensive studies and analyses into the molecular features of severe acute respiratory syndrome related coronavirus 2 (SARS-CoV-2) have enhanced the surveillance and investigation of its clusters and transmission worldwide. The whole genome sequencing (WGS) approach is crucial in identifying the source of infection and transmission routes by monitoring the emergence of variants over time and through communities. Varying SARS-CoV-2 genomics capacity and capability levels have been established in public health laboratories across different Australian states and territories.

Key parameters for genomics-based real-time detection and tracking of multidrug-resistant bacteria: a systematic analysis.

Background: Pairwise single nucleotide polymorphisms (SNPs) are a cornerstone of genomic approaches to the inference of transmission of multidrug-resistant (MDR) organisms in hospitals. However, the impact of many key analytical approaches on these inferences has not yet been systematically assessed. This study aims to make such a systematic assessment.

Future-proofing and maximizing the utility of metadata: The PHA4GE SARS-CoV-2 contextual data specification package.

Background: The Public Health Alliance for Genomic Epidemiology (PHA4GE) (https://pha4ge.org) is a global coalition that is actively working to establish consensus standards, document and share best practices, improve the availability of critical bioinformatics tools and resources, and advocate for greater openness, interoperability, accessibility, and reproducibility in public health microbial bioinformatics. In the face of the current pandemic, PHA4GE has identified a need for a fit-for-purpose, open-source SARS-CoV-2 contextual data standard.

AusTrakka: Fast-tracking nationalized genomics surveillance in response to the COVID-19 pandemic.

The COVID-19 pandemic has driven demand for integrated genomics, resulting in fast-tracked development of AusTrakka, Australia’s pathogen genomics platform. This facilitated rapid data sharing, democratised access to computational and bioinformatic resources and expertise, and achieved national real-time genomic surveillance.

Genomic Epidemiology and Antimicrobial Resistance Mechanisms of Imported Typhoid in Australia.

Typhoid fever is an invasive bacterial disease of humans that disproportionately affects low- and middle-income countries. Antimicrobial resistance (AMR) has been increasingly prevalent in recent decades in Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, limiting treatment options.

Evolutionary dynamics of multidrug resistant Salmonella enterica serovar 4,[5],12:i:- in Australia.

Salmonella enterica serovar 4,[5],12:i:- (Salmonella 4,[5],12:i:-) is a monophasic variant of Salmonella Typhimurium that has emerged as a global cause of multidrug resistant salmonellosis. We used Bayesian phylodynamics, genomic epidemiology, and phenotypic characterization to describe the emergence and evolution of Salmonella 4,[5],12:i:- in Australia. We show that the interruption of the genetic region surrounding the phase II flagellin, FljB, causing a monophasic phenotype, represents a stepwise evolutionary event through the accumulation of mobile resistance elements with minimal impairment to bacterial fitness.

Proficiency testing for bacterial whole genome sequencing in assuring the quality of microbiology diagnostics in clinical and public health laboratories.

The adoption of whole genome sequencing (WGS) data over the past decade for pathogen surveillance, and decision-making for infectious diseases has rapidly transformed the landscape of clinical microbiology and public health. However, for successful transition to routine use of these techniques, it is crucial to ensure the WGS data generated meet defined quality standards for pathogen identification, typing, antimicrobial resistance detection and surveillance. Further, the ongoing development of these standards will ensure that the bioinformatic processes are capable of accurately identifying and characterising organisms of interest, and thereby facilitate the integration of WGS into routine clinical and public health laboratory setting.

Genomics-informed responses in the elimination of COVID-19 in Victoria, Australia: an observational, genomic epidemiological study.

Background: A cornerstone of Australia's ability to control COVID-19 has been effective border control with an extensive supervised quarantine programme. However, a rapid recrudescence of COVID-19 was observed in the state of Victoria in June, 2020. We aim to describe the genomic findings that located the source of this second wave and show the role of genomic epidemiology in the successful elimination of COVID-19 for a second time in Australia.

Prolonged Outbreak of Multidrug-Resistant Shigella sonnei Harboring in Victoria, Australia.

In Australia, cases of shigellosis usually occur in returned travelers from regions of shigellosis endemicity or in men who have sex with men. Resistance to multiple antibiotics has significantly increased in isolates and represents a significant public health concern. We investigate an outbreak of multidrug-resistant in Victoria, Australia.

Tracking the COVID-19 pandemic in Australia using genomics.

Genomic sequencing has significant potential to inform public health management for SARS-CoV-2. Here we report high-throughput genomics for SARS-CoV-2, sequencing 80% of cases in Victoria, Australia (population 6.24 million) between 6 January and 14 April 2020 (total 1,333 COVID-19 cases).

Search and Contain: Impact of an Integrated Genomic and Epidemiological Surveillance and Response Program for Control of Carbapenemase-producing Enterobacterales.

Background: Multiresistant organisms (MROs) pose a critical threat to public health. Population-based programs for control of MROs such as carbapenemase-producing Enterobacterales (CPE) have emerged and evaluation is needed. We assessed the feasibility and impact of a statewide CPE surveillance and response program deployed across Victoria, Australia (population 6.

Mining the Methylome Reveals Extensive Diversity in Staphylococcus epidermidis Restriction Modification.

is a significant opportunistic pathogen of humans. Molecular studies in this species have been hampered by the presence of restriction-modification (RM) systems that limit introduction of foreign DNA. Here, we establish the complete genomes and methylomes for seven clinically significant, genetically diverse isolates and perform the first systematic genomic analyses of the type I RM systems within both and Our analyses revealed marked differences in the gene arrangement, chromosomal location, and movement of type I RM systems between the two species.

Genomics for Molecular Epidemiology and Detecting Transmission of Carbapenemase-Producing in Victoria, Australia, 2012 to 2016.

Carbapenemase-producing (CPE) are being increasingly reported in Australia, and integrated clinical and genomic surveillance is critical to effectively manage this threat. We sought to systematically characterize CPE in Victoria, Australia, from 2012 to 2016. Suspected CPE were referred to the state public health laboratory in Victoria, Australia, from 2012 to 2016 and examined using phenotypic, multiplex PCR and whole-genome sequencing (WGS) methods and compared with epidemiological metadata.

Emergence and divergence of major lineages of Shiga-toxin-producing Escherichia coli in Australia.

Shiga-toxin-producing Escherichia coli (STEC) infection is an important global cause of foodborne disease. To date however, genomics-based studies of STEC have been predominately focused upon STEC collected in the Northern Hemisphere. Here, we demonstrate the population structure of 485 STEC isolates in Australia, and show that several clonal groups (CGs) common to Australia were infrequently detected in a representative selection of contemporary STEC genomes from around the globe.

Pleistocene-dated biogeographic barriers drove divergence within the Australo-Papuan region in a sex-specific manner: an example in a widespread Australian songbird.

Understanding how environmental change has shaped species evolution can inform predictions of how future climate change might continue to do so. Research of widespread biological systems spanning multiple climates that have been subject to environmental change can yield generalizable inferences about the neutral and adaptive processes driving lineage divergence during periods of environmental change. We contribute to the growing body of multi-locus phylogeographic studies investigating the effect of Pleistocene climate change on species evolution by focusing on a widespread Australo-Papuan songbird with several mitochondrial lineages that diverged during the Pleistocene, the grey shrike-thrush (Colluricincla harmonica).

Remodeling of pSK1 Family Plasmids and Enhanced Chlorhexidine Tolerance in a Dominant Hospital Lineage of Methicillin-Resistant .

is a significant human pathogen whose evolution and adaptation have been shaped in part by mobile genetic elements (MGEs), facilitating the global spread of extensive antimicrobial resistance. However, our understanding of the evolutionary dynamics surrounding MGEs, in particular, how changes in the structure of multidrug resistance (MDR) plasmids may influence important staphylococcal phenotypes, is incomplete. Here, we undertook a population and functional genomics study of 212 methicillin-resistant (MRSA) sequence type 239 (ST239) isolates collected over 32 years to explore the evolution of the pSK1 family of MDR plasmids, illustrating how these plasmids have coevolved with and contributed to the successful adaptation of this persistent MRSA lineage.

Persistent low avian malaria in a tropical species despite high community prevalence.

Malarial and other haemosporidian parasites are widespread; however, their temporal dynamics are ill-understood. Longitudinal sampling of a threatened riparian bird revealed a consistently very low prevalence over 13 years (∼5%) despite infections persisting and prevalence increasing with age. In contrast, three key species within this tropical community were highly infected (∼20-75% prevalence) and these differences were stable.

Reconstruction of the Genomes of Drug-Resistant Pathogens for Outbreak Investigation through Metagenomic Sequencing.

Culture-independent methods that target genome fragments have shown promise in identifying certain pathogens, but the holy grail of comprehensive pathogen genome detection from microbiologically complex samples for subsequent forensic analyses remains a challenge. In the context of an investigation of a nosocomial outbreak, we used shotgun metagenomic sequencing of a human fecal sample and a neural network algorithm based on tetranucleotide frequency profiling to reconstruct microbial genomes and tested the same approach using rectal swabs from a second patient. The approach rapidly and readily detected the genome of carbapenemase (KPC)-producing in the patient fecal specimen and in the rectal swab sample, achieving a level of strain resolution that was sufficient for confident transmission inference during a highly clonal outbreak.