scholarly journals RNA polymerases in strict endosymbiont bacteria with extreme genome reduction show distinct erosions that could result in limited and differential promoters’ recognition

2020 ◽  
Author(s):  
Cynthia Paola Rangel-Chávez ◽  
Edgardo Galán-Vásquez ◽  
Azucena Pescador-Tapia ◽  
Luis Delaye ◽  
Agustino Martínez-Antonio

AbstractStrict endosymbiont bacteria with high degree of genome reduction retain smaller proteins and, in certain cases, lack complete functional domains compared to their free-living counterparts. Until now, the mechanisms underlying these genetic reductions are not well understood. However, it is thought that, in order to compensate for gene reduction, somehow hosts take over those vital functions that endosymbionts cannot perform. In the present study, the conservation of RNA polymerases, the essential machinery for gene expression, is analysed in bacteria with extreme genome reductions. For this purpose, comparative genomics, phylogenetic analysis and three-dimensional models of RNA polymerase subunits were done over four lineages of endosymbiotic proteobacteria with the smallest genomes known to date. Amino acids under positive selection in the α subunit and loss of motifs in other subunits of RNA polymerase were observed. According to three-dimensional models, sites under positive selection might compensate the loss of motifs in α subunit. In addition, variations in the σ subunit were identified, some of them already studied in E. coli as a result of random mutagenesis. Amino acid changes in RNA polymerase suggest a possible modification in the binding specificity of the canonical −10 box (TATAAT) in some of these organisms. Furthermore, the β-flap helix domain is absent in some Hodgkinia strains, as observed in RNA pol II of Archaea, thus lacking the capacity to bind to the −35 box. Here, we propose several RNA polymerases models for endosymbiont bacteria with extremely reduced genomes. Evidence suggests that RNA polymerases of each endosymbiont bacteria follow a unique evolutionary path, without necessarily following the same path as a lineage, this is probably influenced by the intimate interactions sustained with other endosymbionts and its hosts.

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0239350
Author(s):  
Cynthia Paola Rangel-Chávez ◽  
Edgardo Galán-Vásquez ◽  
Azucena Pescador-Tapia ◽  
Luis Delaye ◽  
Agustino Martínez-Antonio

Strict endosymbiont bacteria present high degree genome reduction, retain smaller proteins, and in some instances, lack complete functional domains compared to free-living counterparts. Until now, the mechanisms underlying these genetic reductions are not well understood. In this study, the conservation of RNA polymerases, the essential machinery for gene expression, is analyzed in endosymbiont bacteria with extreme genome reductions. We analyzed the RNA polymerase subunits to identify and define domains, subdomains, and specific amino acids involved in precise biological functions known in Escherichia coli. We also perform phylogenetic analysis and three-dimensional models over four lineages of endosymbiotic proteobacteria with the smallest genomes known to date: Candidatus Hodgkinia cicadicola, Candidatus Tremblaya phenacola, Candidatus Tremblaya Princeps, Candidatus Nasuia deltocephalinicola, and Candidatus Carsonella ruddii. We found that some Hodgkinia strains do not encode for the RNA polymerase α subunit. The rest encode genes for α, β, β’, and σ subunits to form the RNA polymerase. However, 16% shorter, on average, respect their orthologous in E. coli. In the α subunit, the amino-terminal domain is the most conserved. Regarding the β and β’ subunits, both the catalytic core and the assembly domains are the most conserved. However, they showed compensatory amino acid substitutions to adapt to changes in the σ subunit. Precisely, the most erosive diversity occurs within the σ subunit. We identified broad amino acid substitution even in those recognizing and binding to the -10-box promoter element. In an overall conceptual image, the RNA polymerase from Candidatus Nasuia conserved the highest similarity with Escherichia coli RNA polymerase and their σ70. It might be recognizing the two main promoter elements (-10 and -35) and the two promoter accessory elements (-10 extended and UP-element). In Candidatus Carsonella, the RNA polymerase could recognize all the promoter elements except the -10-box extended. In Candidatus Tremblaya and Hodgkinia, due to the α carboxyl-terminal domain absence, they might not recognize the UP-promoter element. We also identified the lack of the β flap-tip helix domain in most Hodgkinia’s that suggests the inability to bind the -35-box promoter element.


1975 ◽  
Vol 39 (8) ◽  
pp. 544-546
Author(s):  
HL Wakkerman ◽  
GS The ◽  
AJ Spanauf

2020 ◽  
Vol 17 (4) ◽  
pp. 342-351
Author(s):  
Sergio A. Durán-Pérez ◽  
José G. Rendón-Maldonado ◽  
Lucio de Jesús Hernandez-Diaz ◽  
Annete I. Apodaca-Medina ◽  
Maribel Jiménez-Edeza ◽  
...  

Background: The protozoan Giardia duodenalis, which causes giardiasis, is an intestinal parasite that commonly affects humans, mainly pre-school children. Although there are asymptomatic cases, the main clinical features are chronic and acute diarrhea, nausea, abdominal pain, and malabsorption syndrome. Little is currently known about the virulence of the parasite, but some cases of chronic gastrointestinal alterations post-infection have been reported even when the infection was asymptomatic, suggesting that the cathepsin L proteases of the parasite may be involved in the damage at the level of the gastrointestinal mucosa. Objective: The aim of this study was the in silico identification and characterization of extracellular cathepsin L proteases in the proteome of G. duodenalis. Methods: The NP_001903 sequence of cathepsin L protease from Homo sapienswas searched against the Giardia duodenalisproteome. The subcellular localization of Giardia duodenaliscathepsin L proteases was performed in the DeepLoc-1.0 server. The construction of a phylogenetic tree of the extracellular proteins was carried out using the Molecular Evolutionary Genetics Analysis software (MEGA X). The Robetta server was used for the construction of the three-dimensional models. The search for possible inhibitors of the extracellular cathepsin L proteases of Giardia duodenaliswas performed by entering the three-dimensional structures in the FINDSITEcomb drug discovery tool. Results: Based on the amino acid sequence of cathepsin L from Homo sapiens, 8 protein sequences were identified that have in their modular structure the Pept_C1A domain characteristic of cathepsins and two of these proteins (XP_001704423 and XP_001704424) are located extracellularly. Threedimensional models were designed for both extracellular proteins and several inhibitory ligands with a score greater than 0.9 were identified. In vitrostudies are required to corroborate if these two extracellular proteins play a role in the virulence of Giardia duodenalisand to discover ligands that may be useful as therapeutic targets that interfere in the mechanism of pathogenesis generated by the parasite. Conclusion: In silicoanalysis identified two proteins in the Giardia duodenalisprotein repertoire whose characteristics allowed them to be classified as cathepsin L proteases, which may be secreted into the extracellular medium to act as virulence factors. Three-dimensional models of both proteins allowed the identification of inhibitory ligands with a high score. The results suggest that administration of those compounds might be used to block the endopeptidase activity of the extracellular cathepsin L proteases, interfering with the mechanisms of pathogenesis of the protozoan parasite Giardia duodenalis.


2011 ◽  
Vol 49 (4) ◽  
pp. 326-327 ◽  
Author(s):  
Karen A. Eley ◽  
Robin Richards ◽  
Dermot Dobson ◽  
Alf Linney ◽  
Stephen R. Watt-Smith

Sign in / Sign up

Export Citation Format

Share Document