Biology subjects

Barnes, A. C.

Publications and source records attributed to Barnes, A. C..

3 recordsLinked to original sources

bioRxiv2018

Mutators as drivers of adaptation in pathogenic bacteria and a risk factor for host jumps and vaccine escape: insights into evolutionary epidemiology of the global aquatic pathogen Streptococcus iniae

Pathogens continuously adapt to changing host environments where variation in their virulence and antigenicity is critical to their long-term evolutionary success. The emergence of novel variants is accelerated in microbial mutator strains (mutators) deficient in DNA repair genes, most often from mismatch repair and oxidised-guanine repair systems (MMR and OG respectively). Bacterial MMR/OG mutants are abundant in clinical samples and show increased adaptive potential in experimental infection models, yet the role of mutators in the epidemiology and evolution of infectious disease is not well understood. Here we investigated the role of mutation rate dynamics in the evolution of a broad host range pathogen, Streptococcus iniae, using a set of 80 strains isolated globally over 40 years. We have resolved phylogenetic relationships using non-recombinant core genome variants, measured in vivo mutation rates by fluctuation analysis, identified variation in major MMR/OG genes and their regulatory regions, and phenotyped the major traits determining virulence in streptococci. We found that both mutation rate and MMR/OG genotype are remarkably conserved within phylogenetic clades but significantly differ between major phylogenetic lineages. Further, variation in MMR/OG loci correlates with occurrence of atypical virulence-associated phenotypes, infection in atypical hosts (mammals), and atypical tissue of a vaccinated primary hosts (barramundi bone). These findings suggest that mutators are likely to facilitate adaptations preceding major diversification events, and may promote emergence of variation permitting colonisation of a novel host tissue, novel host taxa (host jumps), and immune-escape in the vaccinated host.

microbiology↗

bioRxiv2018

Leucocyte integrins but not caspases or NLR inflammasome are associated with lipopolysaccharide recognition and response in barramundi (Lates calcarifer)

The inflammatory response of fish to LPS is subdued, attributed to absence of TLR4, a key pro-inflammatory receptor for LPS in mammals. Nevertheless, LPS is processed in fish in a T-independent manner and is a protective antigen in fish vaccines, yet pathways for processing LPS in fish remain to be elucidated. Here, we report that caspases and NOD-like receptor inflammasomes typically responsible for LPS recognition and processing in mammals lack critical domains or are absent in barramundi (Lates calcarifer). However, leucocyte integrins MAC-1 and LFA-1 induce pro-inflammatory cytokine expression poststimulation with LPS. Moreover, MAC-1 and LFA-1 were detected on the surface of neutrophil- and lymphocyte-like cells respectively in the barramundi spleen by immunocytochemistry, and leucocytes displaying MAC-1 or LFA-1 bound to Factor X and ESM-1 respectively. Our results implicate MAC-1 and LFA-1 in immune processing of LPS in barramundi and potentially in antigen processing in fish.

immunology↗

bioRxiv2018

Microevolution of aquatic Streptococcus agalactiae ST-261 from Australia indicates dissemination via imported tilapia and ongoing adaptation to marine hosts or environment

Streptococcus agalactiae (GBS) causes disease in a wide range of animals. The serotype 1b lineage is highly adapted to aquatic hosts, exhibiting substantial genome reduction compared with terrestrial con-specifics. Here we sequence genomes from 40 GBS isolates including 25 from wild fish and captive stingrays in Australia, six local veterinary or human clinical isolates, and nine isolates from farmed tilapia in Honduras and compare with 42 genomes from public databases. Phylogenetic analysis based on non-recombinant core genome SNPs indicated that aquatic serotype Ib isolates from Queensland were distantly related to local veterinary and human clinical isolates. In contrast, Australian aquatic isolates are most closely related to a tilapia isolate from Israel, differing by only 63 core-genome SNPs. A consensus minimum spanning tree based on core genome SNPs indicates dissemination of ST-261 from an ancestral tilapia strain, which is congruent with several introductions of tilapia into Australia from Israel during the 1970s and 1980s. Pan-genome analysis identified 1,440 genes as core with the majority being dispensable or strain-specific with non-protein-coding intergenic regions (IGRs) divided amongst core and strain-specific genes. Aquatic serotype Ib strains have lost many virulence factors during adaptation, but six adhesins were well conserved across the aquatic isolates and might be critical for virulence in fish and targets for vaccine development. The close relationship amongst recent ST-261 isolates from Ghana, USA and China with the Israeli tilapia isolate from 1988 implicates the global trade in tilapia seed for aquaculture in the widespread dissemination of serotype Ib fish-adapted GBS.\n\nImportanceStreptococcus agalactiae (GBS) is a significant pathogen of humans and animals. Some lineages have become adapted to particular hosts and serotype Ib is highly specialized to fish. Here we show that this lineage is likely to have been distributed widely by the global trade in tilapia for aquaculture, with probable introduction into Australia in the 1970s and subsequent dissemination in wild fish populations. We report variability in the polysaccharide capsule amongst this lineage, but identify a cohort common surface proteins that may be a focus of future vaccine development to reduce the biosecurity risk in international fish trade.

bioinformatics↗