Effect of human secretory calcium-binding phosphoprotein proline-glutamine rich 1 protein on Porphyromonas gingivalis and identification of its active portions

AbstractThe mouth environment comprises the second most significant microbiome in the body, and its equilibrium is critical in oral health. Secretory calcium-binding phosphoprotein proline-glutamine rich 1 (SCPPPQ1), a protein normally produced by the gingival epithelium to mediate its attachment to teeth, was suggested to be bactericidal. Our aim was to further explore the antibacterial potential of human SCPPPQ1 by characterizing its mode of action and identifying its active portions. In silico analysis showed that it has molecular parallels with antimicrobial peptides. Incubation of Porphyromonasgingivalis, a major periodontopathogen, with the full-length protein resulted in decrease in bacterial number, formation of aggregates and membrane disruptions. Analysis of SCPPPQ1-derived peptides indicated that these effects are sustained by specific regions of the molecule. Altogether, these data suggest that human SCPPPQ1 exhibits antibacterial capacity and provide new insight into its mechanism of action.

Download Full-text

A proline rich protein from the gingival seal around teeth exhibits antimicrobial properties against Porphyromonas gingivalis

Scientific Reports ◽

10.1038/s41598-021-81791-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Aurélien Fouillen ◽

Charline Mary ◽

Katia Julissa Ponce ◽

Pierre Moffatt ◽

Antonio Nanci

Keyword(s):

Porphyromonas Gingivalis ◽

Calcium Binding ◽

Mammalian Cells ◽

Three Dimensional ◽

Antimicrobial Properties ◽

In Silico Analysis ◽

The Body ◽

Dimensional Structure ◽

Molecular Characteristics ◽

Bacterial Number

AbstractThe gingival seal around teeth prevents bacteria from destroying the tooth-supporting tissues and disseminating throughout the body. Porphyromonas gingivalis, a major periodontopathogen, degrades components of the specialized extracellular matrix that mediates attachment of the gingiva to the tooth. Of these, secretory calcium-binding phosphoprotein proline-glutamine rich 1 (SCPPPQ1) protein has a distinctive resistance to degradation, suggesting that it may offer resistance to bacterial attack. In silico analysis of its amino acid sequence was used to explore its molecular characteristics and to predict its two- and three-dimensional structure. SCPPPQ1 exhibits similarities with both proline-rich and cationic antimicrobial proteins, suggesting a putative antimicrobial potential. A combination of imaging approaches showed that incubation with 20 μM of purified SCPPPQ1 decrease bacterial number (p < 0.01). Fluorescence intensity decreased by 70% following a 2 h incubation of Porphyromonas gingivalis with the protein. Electron microscopy analyses revealed that SCPPPQ1 induced bacterial membrane disruption and breaches. While SCPPPQ1 has no effect on mammalian cells, our results suggest that it is bactericidal to Porphyromonas gingivalis, and that this protein, normally present in the gingival seal, may be exploited to maintain a healthy seal and prevent systemic dissemination of bacteria.

Download Full-text

In silico analysis of the aggregation propensity of the SARS-CoV-2 proteome: Insight into possible cellular pathologies

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics ◽

10.1016/j.bbapap.2021.140693 ◽

2021 ◽

pp. 140693

Author(s):

Manuel Flores-León ◽

Diana F. Lázaro ◽

Liana Shvachiy ◽

Anita Krisko ◽

Tiago F. Outeiro

Keyword(s):

In Silico ◽

In Silico Analysis ◽

Aggregation Propensity ◽

Silico Analysis ◽

Insight Into

Download Full-text

A new insight into role of phosphoketolase pathway in Synechocystis sp. PCC 6803

Scientific Reports ◽

10.1038/s41598-020-78475-z ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Anushree Bachhar ◽

Jiri Jablonsky

Keyword(s):

In Silico Analysis ◽

Bioinformatic Analysis ◽

Phosphoglycerate Mutase ◽

Phosphoketolase Pathway ◽

Multi Level ◽

Silico Analysis ◽

Insight Into ◽

Synechocystis Sp ◽

Pcc 6803

AbstractPhosphoketolase (PKET) pathway is predominant in cyanobacteria (around 98%) but current opinion is that it is virtually inactive under autotrophic ambient CO2 condition (AC-auto). This creates an evolutionary paradox due to the existence of PKET pathway in obligatory photoautotrophs. We aim to answer the paradox with the aid of bioinformatic analysis along with metabolic, transcriptomic, fluxomic and mutant data integrated into a multi-level kinetic model. We discussed the problems linked to neglected isozyme, pket2 (sll0529) and inconsistencies towards the explanation of residual flux via PKET pathway in the case of silenced pket1 (slr0453) in Synechocystis sp. PCC 6803. Our in silico analysis showed: (1) 17% flux reduction via RuBisCO for Δpket1 under AC-auto, (2) 11.2–14.3% growth decrease for Δpket2 in turbulent AC-auto, and (3) flux via PKET pathway reaching up to 252% of the flux via phosphoglycerate mutase under AC-auto. All results imply that PKET pathway plays a crucial role under AC-auto by mitigating the decarboxylation occurring in OPP pathway and conversion of pyruvate to acetyl CoA linked to EMP glycolysis under the carbon scarce environment. Finally, our model predicted that PKETs have low affinity to S7P as a substrate.

Download Full-text

Revisiting the Metabolic Capabilities of Bifidobacterium longum susbp. longum and Bifidobacterium longum subsp. infantis from a Glycoside Hydrolase Perspective

Microorganisms ◽

10.3390/microorganisms8050723 ◽

2020 ◽

Vol 8 (5) ◽

pp. 723

Author(s):

Guillermo Blanco ◽

Lorena Ruiz ◽

Hector Tamés ◽

Patricia Ruas-Madiedo ◽

Florentino Fdez-Riverola ◽

...

Keyword(s):

In Silico ◽

Genetic Background ◽

Bifidobacterium Longum ◽

In Silico Analysis ◽

Glycoside Hydrolases ◽

Computational Tools ◽

Beneficial Effects ◽

Silico Analysis ◽

Insight Into

Bifidobacteria are among the most abundant microorganisms inhabiting the intestine of humans and many animals. Within the genus Bifidobacterium, several beneficial effects have been attributed to strains belonging to the subspecies Bifidobacterium longum subsp. longum and Bifidobacterium longum subsp. infantis, which are often found in infants and adults. The increasing numbers of sequenced genomes belonging to these two subspecies, and the availability of novel computational tools focused on predicting glycolytic abilities, with the aim of understanding the capabilities of degrading specific carbohydrates, allowed us to depict the potential glycoside hydrolases (GH) of these bacteria, with a focus on those GH profiles that differ in the two subspecies. We performed an in silico examination of 188 sequenced B. longum genomes and depicted the commonly present and strain-specific GHs and GH families among representatives of this species. Additionally, GH profiling, genome-based and 16S rRNA-based clustering analyses showed that the subspecies assignment of some strains does not properly match with their genetic background. Furthermore, the analysis of the potential GH component allowed the distinction of clear GH patterns. Some of the GH activities, and their link with the two subspecies under study, are further discussed. Overall, our in silico analysis poses some questions about the suitability of considering the GH activities of B. longum subsp. longum and B. longum subsp. infantis to gain insight into the characterization and classification of these two subspecies with probiotic interest.

Download Full-text

Trophoblast glycoprotein is a new candidate gene for Parkinson’s disease

npj Parkinson s Disease ◽

10.1038/s41531-021-00252-0 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Sanghyun Park ◽

Jeong-Eun Yoo ◽

Gyu-Bum Yeon ◽

Jin Hee Kim ◽

Jae Souk Lee ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Candidate Gene ◽

In Silico Analysis ◽

Substantia Nigra Pars Compacta ◽

Behavioral Deficits ◽

Genetic Ablation ◽

Progressive Degeneration ◽

Silico Analysis ◽

Insight Into

AbstractParkinson’s disease (PD) is a movement disorder caused by progressive degeneration of the midbrain dopaminergic (mDA) neurons in the substantia nigra pars compacta (SNc). Despite intense research efforts over the past decades, the etiology of PD remains largely unknown. Here, we discovered the involvement of trophoblast glycoprotein (Tpbg) in the development of PD-like phenotypes in mice. Tpbg expression was detected in the ventral midbrain during embryonic development and in mDA neurons in adulthood. Genetic ablation of Tpbg resulted in mild degeneration of mDA neurons in aged mice (12–14 months) with behavioral deficits reminiscent of PD symptoms. Through in silico analysis, we predicted potential TPBG-interacting partners whose functions were relevant to PD pathogenesis; this result was substantiated by transcriptomic analysis of the SNc of aged Tpbg knockout mice. These findings suggest that Tpbg is a new candidate gene associated with PD and provide a new insight into PD pathogenesis.

Download Full-text

Dysregulation of miR-381-3p and miR-23b-3p in skeletal muscle could be a possible estimator of early post-mortem interval in rats

PeerJ ◽

10.7717/peerj.11102 ◽

2021 ◽

Vol 9 ◽

pp. e11102

Author(s):

Vanessa Martínez-Rivera ◽

Christian A. Cárdenas-Monroy ◽

Oliver Millan-Catalan ◽

Jessica González-Corona ◽

N. Sofia Huerta-Pacheco ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

In Silico Analysis ◽

Forensic Analysis ◽

The Body ◽

Control Group ◽

Post Mortem ◽

Rt Pcr ◽

Post Mortem Interval ◽

Silico Analysis

Background The post-mortem interval (PMI) is the time elapsed since the dead of an individual until the body is found, which is relevant for forensic purposes. The miRNAs regulate the expression of some genes; and due to their small size, they can better support degradation, which makes them suitable for forensic analysis. In the present work, we evaluated the gene expression of miR-381-3p, miR-23b-3p, and miR-144-3p in skeletal muscle in a murine model at the early PMI. Methods We designed a rat model to evaluate the early PMI under controlled conditions. This model consisted in 25 rats divided into five groups of rats, that correspond to the 0, 3, 6, 12 and 24 hours of PMI. The 0 h-PMI was considered as the control group. Muscle samples were taken from each rat to analyze the expression of miR-381-3p, miR-23b-3p, and miR-144-3p by quantitative RT-PCR. The gene expression of each miRNA was expressed as Fold Change (FC) and compared among groups. To find the targets of these miRNAs and the pathways where they participate, we performed an in-silico analysis. From the gene targets of miR-381-3p identified in the silico analysis, the EPC1 gene was selected for gene expression analysis by quantitative RT-PCR in these samples. Also, to evaluate if miR-381-3p could predict the early PMI, a mixed effects model was calculated using its gene expression. Results An upregulation of miR-381-3p was found at 24 h-PMI compared with the control group of 0 h-PMI and (FC = 1.02 vs. FC = 1.96; p = 0.0079). This was the opposite for miR-23b-3p, which had a down-regulation at 24 h-PMI compared to 0 h-PMI (FC = 1.22 vs. FC = 0.13; p = 0.0079). Moreover, the gene expression of miR-381-3p increased throughout the first 24 h of PMI, contrary to miR-23b-3p. The targets of these two miRNAs, participate in biological pathways related to hypoxia, apoptosis, and RNA metabolism. The gene expression of EPC1 was found downregulated at 3 and 12 h of PMI, whereas it remained unchanged at 6 h and 24 h of PMI. Using a multivariate analysis, it was possible to predict the FC of miR-381-3p of all but 6 h-PMI analyzed PMIs. Discussion The present results suggest that miR-23b-3p and miR-381-3p participate at the early PMI, probably regulating the expression of some genes related to the autolysis process as EPC1 gene. Although the miR-381-3p gene expression is a potential estimator of PMI, further studies will be required to obtain better estimates.

Download Full-text