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Palka, M.

Publications and source records attributed to Palka, M..

2 recordsLinked to original sources

Phylogenomic placement and morphological description of a novel phagotrophic euglenid from Hawaii: Hokulea waialensis n. gen. et sp.

Euglenids are a diverse group of flagellated protists that include phagotrophic, osmotrophic, and phototrophic lineages. Understanding the phylogenetic relationships of phagotrophic euglenids is crucial in understanding euglenid evolution as a whole. Yet many relationships within euglenids remain unclear, and further resolution requires extensive sampling, particularly from the deep-branching, paraphyletic group known as ploeotids. Improved resolution of evolutionary relationships among ploeotid taxa is necessary to elucidate the origin and diversification of complex ultrastructural traits (e.g., pellicle, feeding apparatus). Here, we isolated, cultivated and characterized a novel ploeotid species named Hokulea waialensis n. gen. et sp. using light and scanning electron microscopy, single-cell sequencing, and phylogenomic analyses. This new species is relatively small (10-12 {micro}m long) compared to related euglenids, and shares several morphological traits with related species of Alistosa. Both single and multigene phylogenetic reconstructions from single amplified genome data show that Hokulea waialensis n. gen. et sp. is closely related to several environmental small subunit ribosomal DNA (SSU rDNA) sequences, and more broadly to Lentomonas and Decastava.

evolutionary biology↗

Fidaxomicin jams M. tuberculosis RNA polymerase motions needed for initiation via RbpA contacts

Fidaxomicin (Fdx) is an antimicrobial RNA polymerase (RNAP) inhibitor highly effective against Mycobacterium tuberculosis RNAP in vitro, but clinical use of Fdx is limited to treating Clostridium difficile intestinal infections due to poor absorption. To enable structure-guided optimization of Fdx to treat tuberculosis, we report the 3.4 [A] cryo-electron microscopy structure of a complete M. tuberculosis RNAP holoenzyme in complex with Fdx. We find that the actinobacteria general transcription factor RbpA contacts fidaxomycin and explains its strong effect on M. tuberculosis. We present additional structures that define conformational states of M. tuberculosis RNAP between the free apo-holenzyme and the promoter-engaged open complex ready for transcription. The results establish that Fdx acts like a doorstop to jam the enzyme in an open state, preventing the motions necessary to secure promoter DNA in the active site. Our results provide a structural platform to guide development of anti-tuberculosis antimicrobials based on Fdx.

biophysics↗