Dothistromin is a polyketide toxin, produced by a fungal forest pathogen, with structural similarity to the aflatoxin precursor versicolorin B. Biochemical and genetic studies suggested that there are common steps in the biosynthetic pathways for these metabolites and showed similarities between some of the genes. A polyketide synthase gene (pksA) was isolated from dothistromin-producing Dothistroma septosporum by hybridization with an aflatoxin ortholog from Aspergillus parasiticus. Inactivation of this gene in D. septosporum resulted in mutants that could not produce dothistromin but that could convert exogenous aflatoxin precursors, including norsolorinic acid, into dothistromin. The mutants also had reduced asexual sporulation compared to the wild type. So far four other genes are known to be clustered immediately alongside pksA. Three of these (cypA, moxA, avfA) are predicted to be orthologs of aflatoxin biosynthetic genes. The other gene (epoA), located between avfA and moxA, is predicted to encode an epoxide hydrolase, for which there is no homolog in either the aflatoxin or sterigmatocystin gene clusters. The pksA gene is located on a small chromosome of approximately 1.3 Mb in size, along with the dothistromin ketoreductase (dotA) gene.
The
spread of antimicrobial resistance (AMR) is a rapidly growing
threat to humankind on both regional and global scales. As countries
worldwide prepare to embrace a One Health approach to AMR management,
which is one that recognizes the interconnectivity between human,
animal, and environmental health, increasing attention is being paid
to identifying and monitoring key contributing factors and critical
control points. Presently, AMR sensing technologies have significantly
progressed phenotypic antimicrobial susceptibility testing (AST) and
genotypic antimicrobial resistance gene (ARG) detection in human healthcare.
For effective AMR management, an evolution of innovative sensing technologies
is needed for tackling the unique challenges of interconnected AMR
across various and different health domains. This review comprehensively
discusses the modern state-of-play for innovative commercial and emerging
AMR sensing technologies, including sequencing, microfluidic, and
miniaturized point-of-need platforms. With a unique view toward the
future of One Health, we also provide our perspectives and outlook
on the constantly changing landscape of AMR sensing technologies beyond
the human health domain.
We utilised the retrograde transport machinery of neurones to deliver naked plasmid DNA into the central nervous system. A 5.4-kb fragment of the glycine receptor (GlyR) a1 subunit gene was cloned and used to drive the expression of a construct encoding for the enhanced green fluorescent protein (EGFP). Injections of the plasmid DNA in the tongue of mice resulted in the expression of the marker protein in hypoglossal motor neurones, showing that the GlyRa1 promoter sequence is sufficient to drive expression of the transgene. In order to determine the specificity of expression of the 5.4-kb fragment of the GlyR a1 subunit gene promoter, we subsequently injected the plasmid DNA into the mouse central nucleus of the amygdala. This nucleus receives projections from the parabrachial nucleus, a brainstem area that has a high density of GlyRs, and from the insular cortex, a forebrain structure devoid of GlyRs. We observed EGFP-labelled neurones in the parabrachial nucleus, but not in the insular cortex, indicating that the 5.4-kb GlyR a1 subunit gene promoter confers specificity of expression. This approach provides a simple and rapid way to identify, in vivo, promoter elements that mediate neurone-specific gene expression.
Antimicrobial resistance (AMR) threatens modern medicine as we know it. AMR infections may ultimately be untreatable and routine surgeries will become inherently risky1. By 2050 more people may die of drug-resistant infections (DRIs) every year than of cancer, which equates to more than 10 million annual deaths globally2 and the World Bank has estimated that AMR could cost the global economy $1 trillion every year after 2030. DRIs also lead to an increase in the length of hospital stays, the use of more toxic or costly antibiotics and an increased likelihood of death3. BRIC nations (Brazil, Russia, India, China) and socio-economically challenged countries and people who already have higher rates of infectious diseases will feel the greatest impact2. Indeed, AMR has been likened to the 2008 global financial crisis on an annual repeat cycle. That is because the effects of AMR are not just confined to the human medical sector. The veterinary sector is also reliant on the availability of antimicrobials to treat infectious diseases in companion and food-producing animals.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.