Biology subjects

Metcalfe, C.

Publications and source records attributed to Metcalfe, C..

2 recordsLinked to original sources

bioRxiv2023

Virulence and genomic diversity among clinical isolates of ST1 (BI/NAP1/027) Clostridioides difficile

Clostridioides difficile (C. difficile), a leading cause of nosocomial infection, produces toxins that damage the colonic epithelium and results in colitis that varies from mild to fulminant. Variation in disease severity is poorly understood and has been attributed to host factors (age, immune competence and intestinal microbiome composition) and/or virulence differences between C. difficile strains, with some, such as the epidemic BI/NAP1/027 (MLST1) strain, being associated with greater virulence. We tested 23 MLST1(ST1) C. difficile clinical isolates for virulence in antibiotic-treated C57BL/6 mice. All isolates encoded a complete Tcd pathogenicity locus and achieved similar colonization densities in mice. Disease severity varied, however, with 5 isolates causing lethal infections, 16 isolates causing a range of moderate infections and 2 isolates resulting in no detectable disease. The avirulent ST1 isolates did not cause disease in highly susceptible Myd88-/- or germ-free mice. Genomic analysis of the avirulent isolates revealed a 69 base-pair deletion in the N-terminus of the cdtR gene, which encodes a response regulator for binary toxin (CDT) expression. Genetic deletion of the 69 base-pair cdtR sequence in the highly virulent ST1 R20291 C. difficile strain rendered it avirulent and reduced toxin gene transcription in cecal contents. Our study demonstrates that a natural deletion within cdtR attenuates virulence in the epidemic ST1 C. difficile strain without reducing colonization and persistence in the gut. Distinguishing strains on the basis of cdtR may enhance the specificity of diagnostic tests for C. difficile colitis.

microbiology↗

bioRxiv2021

Genomic evidence that blind cavefishes are not wrecks of ancient life

Cavefishes often have modified eyes, from small but otherwise functional, to highly degenerate structures embedded in a connective tissue and covered by skin. Darwin assumed that these animals are wrecks of ancient life, but several genomic studies suggests they are not ancient. The most radical dating shift is for populations of a Mexican cavefish, Astyanax mexicanus, that have been recently estimated to be at the most a few tens of thousands years old. Despite having highly degenerate eyes, the eye-specific genes of A. mexicanus have low levels of decay. Other blind cavefishes we have examined so far are even older, but also can be dated to the Pleistocene. Here, we estimated the age of blindness of two additional fish species by the level of decay of eye-specific genes. Many pseudogenes were identified in the amblyopsid Typhlichthys subterraneus, suggesting that blindness evolved a few million years ago. In contrast, the blind cichlid Lamprologus lethops appears to be a new case of very recent and rapid eye regression, which occurred in deep river water, an environment similar to caves. Genome-wide analyses support the hypothesis that blindness in cavefishes is never very ancient, and ranges from the Early Pliocene to Late Pleistocene. Together with the description of hundreds of cavefish species, our results suggest that surface fishes were able to recurrently and rapidly adapt to caves and similar small dark ecosystems but the resulting highly specialized blind species with a limited distribution may be evolutionary dead-ends in a relatively short time.

evolutionary biology↗