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Bass, K.

Publications and source records attributed to Bass, K..

2 recordsLinked to original sources

Host genetics determines the fate of the Lactobacillaceae population in the small intestine

Whereas innate pattern recognition receptors bind evolutionary conserved moieties shared by diverse groups of microbes, control over closely related microorganisms is likely based on different principles and can be sensitive to genetic variation of the host. While the influence of host genetics on intestinal microbiome composition has been growing in appreciation, understanding of polymorphic mechanisms that regulate individual bacterial lineages requires complex approaches. Using gnotobiotic mouse monocolonized with Ligilactobacillus murinus (ASF361), we found that C57BL/6J (B6) mice harbored significantly more intestinal ASF361 (or other Lactobacillaceae genera) than did BALB/cJ (BALB/c) mice. The difference in ASF361 abundance was independent of adaptive immunity and bacteriotoxic factors. In B6 mice, ASF361 occupied ileal crypts, showed greater expression of adhesion-related molecules, and enriched expression of carbohydrate-metabolism pathways, whereas in BALB/c mice, ASF361 remained largely luminal and enriched expressed genes associated with starvation and stress. These findings highlight the importance of host genetic variation in shaping microbial colonization and suggest that such variation should be considered when evaluating probiotic strains and microbiota transplantation.

microbiology↗

Genome-wide screen overexpressing mycobacteriophage Amelie genes identifies multiple inhibitors of mycobacterial growth

The genome sequences of thousands of bacteriophages have been determined and functions for many of the encoded genes have been assigned based on homology to characterized sequences. However, functions have not been assigned to more than two-thirds of the identified phage genes as they have no recognizable sequence features. Recent genome-wide overexpression screens have begun to identify bacteriophage genes that encode proteins that reduce or inhibit bacterial growth. This study describes the construction of a plasmid-based overexpression library of 76 genes encoded by Cluster K1 mycobacteriophage Amelie, which is genetically similar to Cluster K phages Waterfoul and Hammy recently described in similar screens and closely related to phages that infect clinically important mycobacteria. 26 out of the 76 genes evaluated in our screen, encompassing 34% of the genome, reduced growth of the host bacterium Mycobacterium smegmatis to various degrees. More than one-third of these 26 toxic genes have no known function, and 10 of the 26 genes almost completely abolished host growth upon overexpression. Notably, while several of the toxic genes identified in Amelie shared homologs with other Cluster K phages recently screened, this study uncovered eight previously unknown gene families that exhibit cytotoxic properties, thereby broadening the repertoire of known phage-encoded growth inhibitors. This work, carried out under the HHMI-supported SEA-GENES project (Science Education Alliance Gene-function Exploration by a Network of Emerging Scientists), underscores the importance of comprehensive overexpression screens in elucidating genome-wide patterns of phage gene function and novel interactions between phages and their hosts.

microbiology↗