Identification of bio-active secondary metabolites from Actinobacteria as potential drug targets against Porphyromonas gingivalis in oral squamous cell carcinoma using molecular docking and dynamics study.

Chronic periodontitis caused by the bacteria Porphyromonas gingivalis is thought to be a risk factor for the advancement of oral squamous cell carcinoma (OSCC). Virulence factors of P. gingivalis include gingipains, outer membrane surface lipoproteins, and fimbriae contribute to the activation of oncogenic pathways in OSCC by up-regulating different cytokines. Gingipains (Arg and Lys) proteases have an important role in the activation of proMMP-9, which promotes cellular invasion and metastatic ability of OSCC. Thus gingipains and MMP-9 were actively investigated as potential therapeutic targets in OSCC therapy. Various natural bioactive compounds from Actinobacteria have been explored for their anticancer potential in a variety of cancers, but very few studies have been reported in OSCC. Therefore, the current study is focused to identify potential actinobacterial compounds that can be considered as a therapeutic target against gingipains and inflammatory proteins in OSCC through high-throughput virtual screening, Molecular Docking (MD), and Molecular Dynamics Simulation (MDS) approaches. A total of 179 bioactive secondary metabolites of Actinobacteria were explored for their binding affinity against six virulence proteins of P. gingivalis. The Molecular Docking studies revealed that among 179 metabolites screened, Actinosporin G showed a highly acceptable binding affinity of -7.9 kcal/mol with RgpB (1CVR), and exhibited multi-protein targeting and drug-likeness property and passed level of toxicity. Comprehensive docking interaction of the best top-ranked Actinosporin G with OSCC-related protein targets illustrated high binding affinity towards MMP-9 and JAK-1 proteins among all targeted receptor proteins. The molecular dynamic (MD) simulation has been executed for the metabolite Actinosporin G for both bacterial gingipain (RgpB) and MMP-9 & JAK-1 showed stable intermolecular binding with both hydrogen and hydrophobic interactions. In conclusion, this work suggests that the bioactive secondary metabolite of Actinosporin G from Actinobacteria genera may serve as a promising therapy for P. gingivalis-induced OSCC. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00209-0.

Halotolerant PGPB Staphylococcus sciuri ET101 protects photosynthesis through activation of redox dissipation pathways in Lycopersicon esculentum.

Photosynthesis is known to be seriously affected by salt stress. The stress induced membrane damage leads to disrupted photosynthetic components causing imbalance between production and utilization of ATP/NADPH with generation of ROS leading to photoinhibition and photodamage. In the current study, role of halotolerant plant growth promoting bacteria (PGPB) Staphylococcus sciuri ET101 in protection of photosynthesis in tomato plants during salinity stress was evaluated by analysing changes in antioxidant defense and activation of redox dissipation pathways. Inoculation of S. sciuri ET101 significantly enhanced the growth of tomato plants with significantly higher photosynthetic rates (PN) under normal and salinity stress conditions. Further, increased membrane stability, soluble sugar accumulation and significant decrease in malondialdehyde (MDA) content in leaves of ET101 inoculated tomato plants under normal and salinity were observed along with increased expression of antioxidant genes for efficient ROS detoxification and suppression of oxidative damage. Additionally, salinity induced decrease in rate of photosynthesis (PN) due to lowered chloroplastic CO2 concentration (Cc) attributed by low mesophyll conductance (gm) in uninoculated plants was alleviated by ET101 inoculation showing significantly higher carboxylation rate (Vcmax), RuBP generation (Jmax) and increased photorespiration (PR). The genes involved in photorespiratory process, cyclic electron flow (CEF), and alternative oxidase (AOX) pathway of mitochondrial respiration were abundantly expressed in leaves of ET101 inoculated plants indicating their involvement in protecting photosynthesis from salt stress induced photoinhibition. Collectively, our results indicated that S. sciuri ET101 has the potential in protecting photosynthesis of tomato plants under salinity stress through activation of redox dissipation pathways.

Protection of Photosynthesis by Halotolerant Staphylococcus sciuri ET101 in Tomato (Lycoperiscon esculentum) and Rice (Oryza sativa) Plants During Salinity Stress: Possible Interplay Between Carboxylation and Oxygenation in Stress Mitigation.

Tomato (Lycoperiscon esculentum) and rice (Oryza sativa) are the two most important agricultural crops whose productivity is severely impacted by salinity stress. Soil salinity causes an irreversible damage to the photosynthetic apparatus in plants at all developmental stages leading to significant reduction in agricultural productivity. Reduction in photosynthesis is the primary response that is observed in all glycophytic plants during salt stress. Employment of salt-tolerant plant growth-promoting bacteria (PGPB) is an economical and viable approach for the remediation of saline soils and improvement of plant growth. The current study is aimed towards investigating the growth patterns and photosynthetic responses of rice and tomato plants upon inoculation with halotolerant PGPB Staphylococcus sciuri ET101 under salt stress conditions. Tomato and rice plants inoculated with PGPB showed increased growth rate and stimulated root growth, along with higher transpiration rates (E), stomatal conductance (g s ), and intracellular CO2 accumulation (Ci). Additionally, correlation of relative water content (RWC) to electrolyte leakage (EL) in tomato and rice plants showed decreased EL in inoculated plants during salt stress conditions, along with higher proline and glycine betaine content. Energy dissipation by non-photochemical quenching (NPQ) and increased photorespiration of 179.47% in tomato and 264.14% in rice plants were observed in uninoculated plants subjected to salinity stress. Furthermore, reduced photorespiration with improved salinity tolerance is observed in inoculated plants. The higher rates of photosynthesis in inoculated plants during salt stress were accompanied by increased quantum efficiency (ΦPSII) and maximum quantum yield (F v /F m ) of photosystem II. Furthermore, inoculated plants showed increased carboxylation efficiency of RuBisCO, along with higher photosynthetic electron transport rate (ETR) (J) during salinity stress. Although the total cellular ATP levels are drastically affected by salt stress in tomato and rice plants along with increased reactive oxygen species (ROS) accumulation, the restoration of cellular ATP levels in leaves of inoculated plants along with decreased ROS accumulation suggests the protective role of PGPB. Our results reveal the beneficial role of S. sciuri ET101 in protection of photosynthesis and amelioration of salinity stress responses in rice and tomato plants.