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Brown, P. E.

Publications and source records attributed to Brown, P. E..

3 recordsLinked to original sources

Novel, highly divergent clones in Listeria monocytogenes serotype 4b in North America: Sublineages 782 and 1039, members of the hypervirulent clonal complex 2

Listeria monocytogenes is a Gram-positive bacterial foodborne pathogen responsible for the severe illness listeriosis. Of the 14 L. monocytogenes serotypes, serotype 4b is a major contributor to human listeriosis and encompasses all four leading hypervirulent clonal complexes (CCs), including the ancient, ubiquitous CC2. CC2 is globally dominated by sublineage (SL) 2, responsible for most human CC2-associated cases. Here we describe two other CC2 SLs, SLs 782 and 1039. These SLs are newly recognized, having been reported only since 2002, and to date are encountered exclusively in North America. Phylogenetic analysis revealed that they are strikingly divergent from each other as well as from SL2. SL782 and SL1039 have been implicated in human listeriosis and have also been repeatedly isolated from surface water and wildlife in North America, with several of these environmental strains exhibiting high genomic similarity ([≤]7 core genome allelic mismatches) to strains from human listeriosis. They share an unusual resistance profile towards a panel of Listeria wide-host-range-phages and exhibit several distinct lineage-specific traits. Specifically, SL782 universally lacks a gene otherwise unique to and conserved in serotype 4b and harbors the Listeria pathogenicity island LIPI-4, while SL1039 harbors LIPI-3 and is almost always resistant to tetracycline, harboring the novel Tn916-like transposon Tn916.1039. These and other traits may have driven clonal emergence of SL782 and SL1039, potentially via adaptations in natural ecosystems.

microbiology↗

EnteroBase in 2025: exploring the genomic epidemiology of bacterial pathogens

This paper presents an update on the content, accessibility and analytical tools of the EnteroBase platform for web-based pathogen genome analysis. EnteroBase provides manually curated databases of genome sequence data and associated metadata from currently >1.1 million bacterial isolates, more recently including Streptococcus spp. and Mycobacterium tuberculosis. We have implemented the genome-based detection of antimicrobial resistance determinants and the new bubble plot graphical tool for visualising bacterial genomic population structures, based on pre-computed hierarchical clusters. Access to data and analysis tools is provided through an enhanced graphical user interface and a new application programming interface (RESTful API). EnteroBase is now being developed and operated by an international consortium, to accelerate the development of the platform and ensure the longevity of the resources built. EnteroBase can be accessed at https://enterobase.warwick.ac.uk as well as https://enterobase.dsmz.de. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/608032v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@88ff78org.highwire.dtl.DTLVardef@3c426eorg.highwire.dtl.DTLVardef@2d8481org.highwire.dtl.DTLVardef@5644bb_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

Systemic mutational rescue in Escherichia coli elicited by a valency dependent, high affinity protein DNA interaction

The controlled formation of sequence specific DNA protein complexes is a fundamental feature of most genetic transactions. Studies of the impact of point mutations on the function of individual components, such as repressors, remains a key aspect of many Systems and Synthetic Biology research programmes. One of the most dramatic systemic consequences of a point mutation is exhibited by the monomeric DNA methyltransferases M.HhaI and M.EcoRII, where substitution of a single, catalytic cysteine by either glycine or alanine, creates a lethal gain of function phenotype. In vivo expression of these point mutants promotes the deposition of high affinity nucleoprotein complexes that arrest replication in vivo, causing cell death. Interestingly, it appears that a systemic response to expression of these mutant enzymes is dramatically enhanced when they are expressed as synthetic dimers. A previously unreported form of "mutational rescue" appears to be triggered as a result of networked crosslinking of host cell DNA resulting from an increased valency of nucleoprotein complex formation. This finding may have significance for developing molecular interventions for the controlled regulation of genome function and for the development of novel antimicrobial and anticancer strategies.

genomics↗