The glutathione import system satisfies the Staphylococcus aureus nutrient sulfur requirement and promotes interspecies competition

Sulfur is an indispensable element for proliferation of bacterial pathogens. Prior studies indicated that the human pathogen, Staphylococcus aureus utilizes glutathione (GSH) as a source of nutrient sulfur; however, mechanisms of GSH acquisition are …

MolEvolvR BTS: When and how to build a web-app and software package?

We recently developed a web application, MolEvolvR, to characterize proteins using molecular evolution and phylogeny. This session will serve as a behind-the-scenes (BTS) sneak peek into what MolEvolvR does, how it does it, and its origin story. The …

Feedback in the β-catenin destruction complex imparts bistability and cellular memory

Positive feedback within the β-catenin destruction complex gives rise to bistability and memory in response to Wnt stimulation, imparting signal transduction accuracy and insulation.

Phage defence by deaminase-mediated depletion of deoxynucleotides in bacteria

DciA Helicase Operators Exhibit Diversity across Bacterial Phyla

Despite the fundamental importance of DNA replication for life, this process remains understudied in bacteria outside Escherichia coli and Bacillus subtilis. In particular, most bacteria do not encode the helicase-loading proteins that are essential in E. coli and B. subtilis for DNA replication. Instead, most bacteria encode a DciA homolog that likely constitutes the predominant mechanism of helicase operation in bacteria. However, it is still unknown how DciA structure and function compare across diverse phyla that encode DciA proteins. In this study, we performed computational evolutionary analyses to uncover tremendous diversity among DciA homologs. These studies provide a significant advance in our understanding of an essential component of the bacterial DNA replication machinery.

Novel Internalin P homologs in Listeria ivanovii londoniensis and Listeria seeligeri

The intracellular bacterial pathogen Listeria monocytogenes can breach protective barriers in the pregnant host, allowing the colonization of the placenta in pregnant people and resulting in numerous adverse pregnancy outcomes. Previous studies aimed at delineating the mechanisms behind placental colonization of L. monocytogenes identified a key virulence factor, internalin P (InlP). The internalin family of proteins has been studied extensively due to their conservation in the genus Listeria and their contribution to virulence and pathogenicity in L. monocytogenes. Still, many questions remain regarding the evolution of internalins and their potential roles in non-pathogenic Listeria. Our work addresses this gap in knowledge by (1) identifying additional InlP homologs in Listeria, including L. ivanovii, L. seeligeri, L. innocua, and L. costaricensis, and (2) characterizing these homologs using computational evolutionary methods to compare their primary sequences, domain architectures, and structural models. Together, our findings contribute to the field by providing insights into the evolution of one key member of the internalin family, as well as serving as a catalyst for future studies of InlP and its role in Listeria pathogenesis.

Cross-database integration using evolution and machine learning to identify multiscale molecular building blocks for antibiotic resistance

MolEvolvR: a web-app for characterizing proteins using molecular evolution and phylogeny

Studying proteins through the lens of evolution can help identify conserved features and lineage-specific variants, and potentially, their functions. MolEvolvR ( is a web-app that enables researchers to run a …

Computational approaches to study molecular pathogenesis and intervention of infectious diseases

Reconciling Multiple Connectivity Scores for Drug Repurposing

The basis of several recent methods for drug repurposing is the key principle that an efficacious drug will reverse the disease molecular 'signature' with minimal side effects. This principle was defined and popularized by the influential …