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Saha, C.

Publications and source records attributed to Saha, C..

2 recordsLinked to original sources

An efflux pump family distributed across plant commensal bacteria conditions host- and organ-specific detoxfication of a host-specific glucosinolate

In nature, plants recruit a diverse microbial community, the plant microbiome, that is distinct from the surrounding soil community 1-4. To understand the forces that shape the plant microbiome we need to characterize the microbial traits that contribute to plant colonization. We used barcoded mutant libraries to identify bacterial genes that contribute to the colonization of a monocot and a eudicot host 5-7. We show that plant colonization is influenced by dozens of genes. While some of these colonization genes were shared between the two host plant species, most were highly specific, benefiting the colonization of a single host and organ. We characterized an efflux pump that specifically contributes to Arabidopsis shoot colonization. This efflux pump is prevalent across Pseudomonadota genomes, yet benefits the bacterial association with only a small subset of Arabidopsis thaliana accessions. Leveraging genomic diversity within Arabidopsis thaliana, we confirmed that specific glucosinolate breakdown products are detoxified by this family of efflux pumps. The broad prevalence of this efflux pump family suggests that its members contribute to protection of commensal bacteria from collateral damage of plant glucosinolate-based defense responses to herbivores and necrotrophic pathogens.

microbiology↗

Decoding the Effects of Spike Receptor Binding Domain Mutations on Antibody Escape Abilities of Omicron Variants

Recent times witnessed an upsurge in the number of COVID cases which is primarily attributed to the emergence of several omicron variants, although there is substantial population vaccination coverage across the globe. Currently, many therapeutic antibodies have been approved for emergency usage. The present study critically evaluates the effect of mutations observed in several omicron variants on the binding affinities of different classes of RBD-specific antibodies using a combined approach of immunoinformatics and binding free energy calculations. Our binding affinity data clearly show that omicron variants achieve antibody escape abilities by incorporating mutations at the immunogenic hotspot residues for each specific class of antibody. K417N and Y505H point mutations are primarily accountable for the loss of class I antibody binding affinities. The K417N/Q493R/Q498R/Y505H combined mutant significantly reduces binding affinities for all the class I antibodies. E484A single mutation, on the other hand, drastically reduces binding affinities for most of the class II antibodies. E484A and E484A/Q493R double mutations cause a 33-38% reduction in binding affinity for the approved therapeutic monoclonal antibodies, Bamlanivimab (LY-CoV555). The Q498R RBD mutation observed across all the omicron variants can reduce ~12% binding affinity for REGN10987, a class III therapeutic antibody, and the L452R/Q498R double mutation causes a ~6% decrease in binding affinities for another class III therapeutic antibody, LY-CoV1404. Our data suggest that achieving the immune evasion abilities appears to be the selection pressure behind the emergence of omicron variants.

bioinformatics↗