Publications by authors named "Jake Lacey"

We describe two locally acquired cases of Mycobacterium ulcerans infection (Buruli ulcer) in the town of Batemans Bay on the east coast of New South Wales (NSW), Australia, 150 km north of Eden, the only other place in NSW where Buruli ulcer has likely been locally acquired. Genomic analysis showed that the bacterial isolates from the cases were identical but belonged to a phylogenetically distinct M. ulcerans clade that was most closely related to the isolate from the earlier case in Eden to the south.

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Background: Fiji is a Pacific Island nation grappling with the increasing threat of antimicrobial resistance (AMR). While genomic technologies are increasingly utilised to understand the emergence and spread of AMR globally, its application to inform outbreak responses in low- and middle-income settings has not been reported.

Methods: Through an established capacity building program, suspected carbapenem-resistant organisms (CRO) identified at Colonial War Memorial Hospital in Fiji (Jan 2022-Oct 2023) underwent whole genome sequencing and analysis.

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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 implemented 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 Typhi in the Northern Division prior to island-wide vaccination, sequencing 85% (=419) of the total cases from the Northern and Central Divisions of Fiji that occurred in the period 2017-2019.

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Article Synopsis
  • The study examines the genomic relationship between Streptococcus dysgalactiae subspecies equisimilis (SDSE) and Streptococcus pyogenes, focusing on how they share ecosystems and possibly diseases due to genetic similarities and horizontal gene transfer (HGT).
  • An analysis of genomes from 294 SDSE and 315 S. pyogenes samples collected in remote Australian First Nations communities reveals a significant overlap in transmission among households, suggesting independent transmission patterns without competition between the two species.
  • The research identifies mobile genetic elements linked to antimicrobial resistance and virulence in both pathogens, emphasizing the ongoing co-circulation of SDSE and S. pyogenes in these communities and highlighting the need
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Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of human infection with invasive disease incidence and clinical manifestations comparable to the closely related species, Streptococcus pyogenes. Through systematic genomic analyses of 501 disseminated SDSE strains, we demonstrate extensive overlap between the genomes of SDSE and S.

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Background: Acute rheumatic fever (ARF) is a serious post-infectious sequala of Group A (GAS, ). In New Zealand (NZ) ARF is a major cause of health inequity. This study describes the genomic analysis of GAS isolates associated with childhood skin and throat infections in Auckland NZ.

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After introduction of faecal multiplex PCR that includes targets for stx1 and stx2 genes, we found stx genes were detected in 120 specimens from 111 patients over a 31-month period from 2018-2020 from a total of 14,179 separate tests performed. The proportion of stx1 only vs stx2 only vs stx1 and stx2 was 35%, 22% and 42%, respectively. There were 54 specimens which were culture positive, with 33 different serotypes identified, the predominant serotype being O157:H7 (19%).

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Article Synopsis
  • Streptococcus pyogenes (GAS) infections significantly impact Aboriginal Australians, leading to skin infections and serious health issues like rheumatic heart disease, but understanding their transmission has been challenging.
  • A genomic analysis of GAS isolates from a study on impetigo in remote Northern Territory communities revealed that asymptomatic throat carriage plays a larger role in GAS transmission compared to impetigo lesions.
  • Findings indicated households experienced prolonged GAS infections, often reinforced by factors like household size and the presence of other infections, complicating efforts to control these infections.
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  • A new variant of Streptococcus pyogenes serotype M1 has been identified in the UK, linked to increases in scarlet fever cases and invasive infections due to its enhanced SpeA superantigen expression.
  • This M1 variant can be distinguished from its predecessor by specific genetic mutations but the reason for the increased SpeA expression remains unclear.
  • Researchers found that a single genetic change in the ssrA gene leads to higher SpeA expression in the M1 lineage in Australia, signaling a need for better global monitoring of such variants.
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  • M and M-like proteins are crucial for the virulence of Group A Streptococcus (GAS) and serve as key markers for studying this pathogen.
  • Analysis of 1668 GAS genomes led to the identification of four major protein groupings (M-family-groups) which consist of various proteins, including M, Mrp, and Enn proteins, each with unique evolutionary histories.
  • The study found complex co-occurrence patterns among these proteins, indicating that their evolution is influenced by functional and virulence factors, with Mrp being the most genetically distinct among the groups.
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  • Bacteria can develop resistance to antibiotics through various mechanisms, which can be monitored by laboratory tests.
  • This study identifies a specific resistance mechanism in Group A Streptococcus that uses a gene (thfT) to acquire nutrients from the host, allowing it to bypass the antibiotic sulfamethoxazole's effects.
  • Understanding these resistance mechanisms during infections is crucial to reduce ineffective antibiotic use and limit the spread of resistance among bacteria.
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Background: Typhoid fever is endemic in some Pacific Island Countries including Fiji and Samoa yet genomic surveillance is not routine in such settings. Previous studies suggested imports of the global H58 clade of var Typhi ( Typhi) contribute to disease in these countries which, given the MDR potential of H58, does not auger well for treatment. The objective of the study was to define the genomic epidemiology of Typhi in Fiji.

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Background: Common infections of the skin such as impetigo and scabies represent a large burden of disease globally, being particularly prevalent in tropical and resource-limited settings. Efforts to address these infections through mass drug administrations have recently been shown as efficacious and safe. In Samoa, a Pacific Island nation, there is a marked lack of epidemiological data for these neglected tropical diseases, or appreciation of their drivers in this setting.

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The emergence of polymyxin resistance in carbapenem-resistant and extended-spectrum β-lactamase (ESBL)-producing bacteria is a critical threat to human health, and alternative treatment strategies are urgently required. We investigated the ability of the hydroxyquinoline analog ionophore PBT2 to restore antibiotic sensitivity in polymyxin-resistant, ESBL-producing, carbapenem-resistant Gram-negative human pathogens. PBT2 resensitized , , , and to last-resort polymyxin class antibiotics, including the less toxic next-generation polymyxin derivative FADDI-287, in vitro.

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Streptococcus pyogenes is one of the Top 10 human infectious disease killers worldwide causing a range of clinical manifestations in humans. Colonizing a range of ecological niches within its sole host, the human, is key to the ability of this opportunistic pathogen to cause direct and post-infectious manifestations. The expansion of genome sequencing capabilities and data availability over the last decade has led to an improved understanding of the evolutionary dynamics of this pathogen within a global framework where epidemiological relationships and evolutionary mechanisms may not be universal.

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Group A Streptococcus (GAS) skin infections are caused by a diverse array of strain types and are highly prevalent in disadvantaged populations. The role of strain-specific immunity in preventing GAS infections is poorly understood, representing a critical knowledge gap in vaccine development. A recent GAS murine challenge study showed evidence that sterilising strain-specific and enduring immunity required two skin infections by the same GAS strain within three weeks.

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Whole-genome sequencing (WGS) is used to determine the genetic composition of an organism. This fast-moving field is continually evolving through technical advancements and the development of new bioinformatic tools for analyzing genomic data; however, the basic principles and processes for defining and processing high-quality genome sequence information remain unchanged. Here, we introduce some considerations and describe some commonly used bioinformatic steps for processing raw genome sequence data to generate genome assemblies through to understanding basic population genomics.

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A recent clinical report has linked β-lactam antibiotic resistance to mutation in the penicillin binding protein (PBP) PBP2x. To determine whether this is an isolated case or reflects a broader prevalence of mutations that might confer reduced β-lactam susceptibility, we investigated the relative frequency of PBP sequence variation within a global database of 9,667 isolates. We found that mutations in PBPs (PBP2x, PBP1a, PBP1b, and PBP2a) occur infrequently across this global database, with fewer than 3 amino acid changes differing between >99% of the global population.

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In Gram-negative bacteria, the permeability of the outer membrane governs rates of antibiotic uptake and thus the efficacy of antimicrobial treatment. Hydrophilic drugs like β-lactam antibiotics depend on diffusion through pore-forming outer membrane proteins to reach their intracellular targets. In this study, we investigated the distribution of porin genes in more than 2,700 isolates and found a widespread loss of OmpK35 functionality, particularly in those strains isolated from clinical environments.

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Focal duodenal necrosis (FDN) is an intestinal disease of egg-layer chickens characterized by multifocal necrosis of the duodenal loop and proximal jejunum. Affected flocks usually have decreased egg weights and drops in egg production. Previous studies have associated this condition with infection.

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Article Synopsis
  • Group A Streptococcus is a significant global health threat, and the dynamics of its infections, colonization, and immunity are still being studied.
  • The M protein, linked to the emm gene, is a key factor in the bacteria's virulence and is a potential vaccine target.
  • A study on Fijian schoolchildren showed no specific tissue preferences for different emm types and indicated that prior infections may not greatly influence future susceptibility to infections.
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Whole-genome sequences are now available for all the clinically important clostridia and many of the lesser or opportunistically pathogenic clostridia. The complex clade structures of , , and the species that produce botulinum toxins have been delineated by whole-genome sequence analysis. The true clostridia of cluster I show relatively low levels of gross genomic rearrangements within species, in contrast to the species of cluster XI, notably , which have been found to have very plastic genomes with significant levels of chromosomal rearrangement.

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