Intrinsic Antiviral Activity of Optineurin Prevents Hyperproliferation of a Primary Herpes Simplex Virus Type 2 Infection.

Very little knowledge exists on virus-specific host cell intrinsic mechanisms that prevent hyperproliferation of primary HSV type 2 (HSV-2) genital infections. In this study, we provide evidence that the Nemo-related protein, optineurin (OPTN), plays a key role in restricting HSV-2 infection both in vitro and in vivo. Contrary to previous reports regarding the proviral role of OPTN during Sendai virus infection, we demonstrate that lack of OPTN in cells causes enhanced virus production. OPTN deficiency negatively affects the host autophagy response and results in a marked reduction of CCL5 induction. OPTN knockout (OPTN-/-) mice display exacerbated genital disease and dysregulated T cell frequencies in infected tissues and lymph nodes. A human transcriptomic profile dataset provides further credence that a strong positive correlation exists between CCL5 upregulation and OPTN expression during HSV-2 genital infection. Our findings underscore a previously unknown OPTN/CCL5 nexus that restricts hyperproliferative spread of primary HSV-2 infection, which may constitute an intrinsic host defense mechanism against herpesviruses in general.

Bacterial Pigment Prodigiosin Demonstrates a Unique Antiherpesvirus Activity That Is Mediated through Inhibition of Prosurvival Signal Transducers.

Herpes simplex virus (HSV) is among the most prevalent viral infections worldwide and remains incurable. While nucleoside analogs are used to relieve symptoms of infection, they suffer from having serious adverse effects and are unable to abolish the virus from the host. Here, we demonstrate a unique antiviral effect of prodigiosin (PG), a natural secondary metabolite produced by Serratia marcescens, on HSV infection. We show that PG naturally exerts antiviral activity against HSV-1 and HSV-2 infections. PG treatment resulted in robust inhibition of viral replication in vitro and ex vivo in cultured porcine corneas. Additionally, PG protected against HSV-1 infection and disease progression in a murine model of ocular infection. In our quest to determine the molecular mechanisms of its antiviral activity, we show that PG specifically inhibits NF-κB and Akt signaling pathways and promotes accelerated cell death in HSV-infected cells. Our findings reveal novel antiviral properties of PG, suggesting its high potential as an alternative treatment for herpetic diseases. They also provide new information on antiviral effects of HSV-bacterial metabolite interactions.IMPORTANCE In this article, we provide a new role for a commonly found bacterial pigment in controlling herpes simplex virus infection, for which diverse and multimodal antiviral agents are needed to prevent drug resistance. Serratia marcescens is a red pigment (prodigiosin)-producing Gram-negative bacillus that is naturally found in soil and water. It is associated with many kinds of human infections, including wound and eye infections, and meningitis. Taking cues from previous studies on prodigiosin, including possible proapoptotic anticancer properties, we investigated how it might affect HSV infection. Interestingly, we found that it is a potent virucidal compound that disrupts host signaling pathways needed for HSV growth and survival. The mode of antiviral action suggests potentially broad activity against enveloped viruses. Our results also indicate that interactions with commensal bacteria may inhibit HSV infection, underscoring the importance of studying these microbial metabolites and their implications for viral pathogenesis and treatment.

Mechanistic approach for fabrication of gold nanoparticles by Nitzschia diatom and their antibacterial activity.

The problem of chemically synthesized nanoproducts motivated scientific community to explore ecofriendly methods of nanosynthesis. Diatoms belong to a group of aquatic, unicellular, photosynthetic microalgae have been scarcely investigated as a source of reducing and capping agents for nanosynthesis of pesticides and antibiotics. The present study reports a novel ecofriendly method for the fabrication of bioactive gold nanoparticles using locally isolated Nitzschia diatoms. The diatom-fabricated gold nanoparticles show characteristic ruby red colored with sharp absorbance peak at 529 nm. Electron microscopy confirmed irregular shape of gold nanoparticles, with average size of 43 nm and zeta potential of -16.8 mV. The effects of gold nanoparticles on diatom viability were investigated using light and electron microscopy. The mechanistic approach to shed light on how diatoms reacted after exposure to gold metal salt revealed that exposure to gold chloride triggers elevated levels of catalase and peroxidase (12.76 and 14.43 unit/mg protein, respectively) to relieve reactive oxygen species (ROS) stress induced by gold salt exposure. Investigation studies on mechanisms behind Nitzschia-mediated gold nanoparticles fabrication outlined the role of diatom proteins, polysaccharides in reduction, and stabilization of nanoparticles as confirmed by FT-IR analysis. Bioactivity of gold nanoparticles was accessed by coupling them with antibiotics (penicillin and streptomycin), which increased their antibacterial activity compared to individual nanoparticles and antibiotics (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus). Overall, the present novel phyco-nanotechnological approach is a promising tool to be used as sustainable strategy in green nanotechnology as well as to reduce use of antibiotics in microbial control.

Biofunctionalized silver nanoparticles as a novel colorimetric probe for melamine detection in raw milk.

Nanoparticles have emerged as a promising analytical tool for monitoring food adulteration and safety. In the present study, silver nanoparticles (AgNPs) were synthesized using leaves' extract of Jatropha gossypifolia. AgNPs revealed a characteristic surface plasmon resonance (SPR) peak at 419 nm and have spherical and grain shape with size range between 18 and 30 nm. A selective and rapid method of melamine detection in raw milk was developed with the use of these biofunctionalized AgNPs. The color change, deviation in SPR spectra, and change in the absorption ratio (A500 /A419 ) of AgNPs occurred after an AgNPs-melamine interaction. The detection limit for melamine up to 2 µM (252 ppb) was attained with this method, which is quite lower than safety level recommendations of regulatory bodies demonstrating sensitivity of the method. Dynamicx light scattering and transmission electron microscopy analyses exhibited an increase in hydrodynamic diameter and size of AgNPs after melamine interaction. Melamine sensing by AgNPs was investigated by different physicochemical and thermal analyses.

Innovative approach for urease inhibition by Ficus carica extract-fabricated silver nanoparticles: An in vitro study.

In the present study, a rapid, low-cost, and ecofriendly method of stable silver nanoparticles (AgNPs) synthesis using leaves extract of Ficus carica (F. carica), a plant with diverse metabolic consortium, is reported for the first time. An absorption peak at 422 nm in UV-Vis spectroscopy, a spherical shape with an average size of 21 nm in transmission electron microscopy, and crystalline nature in X-ray powder diffraction studies were observed for the synthesized AgNPs. Fourier transform infrared analysis indicated that proteins of F. carica might have a vital role in AgNP synthesis and stabilization. AgNPs were found to inhibit urease, a key enzyme responsible for the survival and pathogenesis of the bacterium, Helicobacter pylori. Inhibition of urease by AgNPs was monitored spectrophotometrically by the evaluation of ammonia release. The urease inhibition potential of AgNPs can be explored in the treatment of H. pylori by preparing novel combinations of standard drugs with AgNPs- or AgNPs-encapsulated drug molecules.

Mosquito larvicidal and pupaecidal potential of prodigiosin from Serratia marcescens and understanding its mechanism of action.

Mosquitoes spread lethal diseases like malaria and dengue fever to humans. Considering mosquito vector control as one of the best alternatives to reduce new infections, here we have analyzed the effect of purified pigment prodigiosin extracted from Serratia marcescens (NMCC 75) against larval and pupal stages of Aedes aegypti and Anopheles stephensi mosquitoes. Mosquito larvicidal activities of purified prodigiosin revealed LC50 values of 14 ± 1.2, 15.6 ± 1.48, 18 ± 1.3, 21 ± 0.87 µg/ml against early IInd, IIIrd, IVth instar and pupal stages of Ae. aegypti, respectively. LC50 values for An. stephensi were found to be 19.7 ± 1.12, 24.7 ± 1.47, 26.6 ± 1.67, 32.2 ± 1.79 µg/ml against early IInd, IIIrd, IVth instar and pupae of An. stephensi, respectively. Further investigations toward understanding modes of action revealed variations in the activities of esterases, acetylcholine esterases, phosphatases, proteases and total proteins in the fourth instar larvae of Ae. aegypti indicating intrinsic difference in biochemical features due to prodigiosin treatment. Although there was no inhibition of enzymes like catalase and oxidase but may have profound inhibitory effect on carbonic anhydrase or H(+)-V-ATPase which is indicated by change in the pH of midgut and caeca of mosquito larvae. This reduced pH may be possibly due to the proton pump inhibitory activity of prodigiosin. Pure prodigiosin can prove to be an important molecule for mosquito control at larval and pupal stages of Ae. aegypti and An. stephensi. This is the first report on the mosquito pupaecidal activity of prodigiosin and its possible mechanism of action.

Transformation of aromatic dyes using green synthesized silver nanoparticles.

Nowadays, increasing use of nanoproducts in area of human and environmental applications raises concern about safety aspects of nanoparticles synthesized using traditional physicochemical methods. Silver nanoparticles (AgNPs) synthesis at ambient parameters using latex of medicinally important plant Jatropha gossypifolia (J. gossypifolia) is reported in the present study. Potential of AgNPs in degradation of methylene blue and eosin B was also evaluated. Rapid formation of stable AgNPs was analyzed by visual color change from colorless to yellow-red after addition of latex in AgNO3 solution and by characteristic surface plasmon resonance (SPR) peak at 430 nm in UV-Vis spectroscopy. FT-IR analysis, protein coagulation test showed capping of proteins, flavonoids, terpenoids and polyphenols of latex on surface of AgNPs. FE-SEM, HR-TEM analysis revealed spherical shape of AgNPs. Narrow size range of AgNPs (5-40 nm) observed in HR-TEM analysis. EDS analysis confirms the presence of elemental silver while XRD revealed crystalline nature of AgNPs. Zeta potential of -21.4 mV indicates high stability of AgNPs. Effects of different parameters (pH, temperature, incubation time) on nanosynthesis were studied in the present study. Dye reduction studies were performed using UV-Vis spectroscopy, TLC, FT-IR and HPLC analysis showing decreased absorbance maxima of both dyes with respect to time, change in R f values, changes in wave number, transmittance, and retention time of dyes after AgNPs addition. The rate constant for methylene blue and eosin B reduction by AgNPs was found to be 0.062 and 0.022 min(-1).

Mercury sensing and toxicity studies of novel latex fabricated silver nanoparticles.

Safe and eco-friendly alternatives to currently used hazardous chemico-physical methods of silver nanoparticles (AgNPs) synthesis are need of time. Rapid, low cost, selective detection of toxic metals in environmental sample is important to take safety action. Toxicity assessment of engineered AgNPs is essential to avoid its side effects on human and non-target organisms. In the present study, biologically active latex from Euphorbia heterophylla (Poinsettia) was utilized for synthesis of AgNPs. AgNPs was of spherical shape and narrow size range (20-50 nm). Occurrence of elemental silver and crystalline nature of AgNPs was analyzed. Role of latex metabolites in reduction and stabilization of AgNPs was analyzed by FT-IR, protein coagulation test and phytochemical analysis. Latex-synthesized AgNPs showed potential in selective and sensitive detection of toxic mercury ions (Hg(2+)) with limit of detection around 100 ppb. Addition of Hg(2+) showed marked deviation in color and surface plasmon resonance spectra of AgNPs. Toxicity studies on aquatic non-target species Daphnia magna showed that latex-synthesized AgNPs (20.66 ± 1.52% immobilization) were comparatively very less toxic than chemically synthesized AgNPs (51.66 ± 1.52% immobilization). Similarly, comparative toxicity study on human red blood cells showed lower hemolysis (4.46 ± 0.01%) by latex-synthesized AgNPs as compared to chemically synthesized AgNPs causing 6.14 ± 0.01% hemolysis.

Rapid NETosis Is an Effector Mechanism to Combat Ocular Herpes Infection.

Purpose: Neutrophils are known mediators of innate immunity, yet their effector function in herpesvirus infections remains poorly understood. Here, we elucidate the mechanistic action and pivotal role of neutrophil extracellular traps (NETs) during herpes simplex virus type 1 (HSV-1) ocular infection. Methods: Neutrophils were collected from mice for HSV-1 infection, fluorescence imaging, and immunoblotting assay. Tear samples from healthy subjects and patients with HSV-1 and mice were collected at L. V. Prasad Eye Institute, India, and at the University of Illinois, USA, respectively. For the in vivo study, C57BL/6 mice as well as diversity outbred mice were infected with HSV-1 (McKrae strain) followed by tear fluid collection at various time points (0-10 days). Samples were used for Flow cytometry, ELISA, and immunofluorescence assay. Human transcriptomic profile of keratitis dataset was used evaluate NETosis signaling pathways. We also performed neutrophil depletion studies. Results: Our data revealed a discernible temporal NET formation (NETosis) predominantly in the infected eye, across normal and diversity outbred murine models and human cases of HSV-1 infection. HSV-1 instigates swift NETosis governed by caspase-1 activation and myeloperoxidase secretion. Distinct accumulations of neutrophils, remaining unengaged in NET release in the contralateral eye post-infection, hinting at a proactive defensive posture in the uninfected eye. Moreover, neutrophil depletion accentuated ocular pathology, augmented viral load, and escalated disease scores, substantiating the protective effects of NETs in curtailing viral replication. Conclusions: Our report uncovers a previously unexplored mechanism of NETosis through pro-inflammatory cell death in response to ocular HSV-1 infection, and HPSE up-regulation, identifying new avenues for future studies.

Alteration in Bacillus thuringiensis toxicity by curing gut flora: novel approach for mosquito resistance management.

Mosquitoes are known for acquiring resistance against insecticides in many ways, namely target side mutation, enzyme modification, sequestration, quick elimination, etc. But, the role of microflora present in abundance in the larval midgut is less explored with respect to their role in insecticide resistance. During the course of their development, mosquitoes are continuously exposed to microbes and have naturally acquired midgut microbial flora. This midgut flora can modulate the mosquito's susceptibility to Bacillus thuringiensis (Bt) infection by degrading toxic Bt protein forms through an unknown mechanism. In this study, we show that microbe-free aseptic mosquito larvae displayed an increased susceptibility to Bt toxicity compared to larvae harboring natural microbial flora. Fourth instar larvae of Anopheles stephensi were treated separately with penicillin, streptomycin, erythromycin (100 µg/ml), and mixtures of all three antibiotics and then analyzed for Bt toxicity. We have also examined the influence of the mosquito's midgut microbial flora under microaerophilic condition on the Bt protein degradation through plate, broth, TLC, and UV-vis spectrophotometric assay. A better understanding of the roles of microbiota in preventing Bt toxicity to mosquitoes could potentially lead to the development of new sustainable mosquito control strategies.

Pathophysiology of reinfection by exogenous HSV-1 is driven by heparanase dysfunction.

Limited knowledge exists on exogenous DNA virus reinfections. Herpes simplex virus-1 (HSV-1), a prototype DNA virus, causes multiple human diseases including vision-threatening eye infections. While reinfection with an exogenous HSV-1 strain is considered plausible, little is known about the underlying mechanisms governing its pathophysiology in a host. Heparanase (HPSE), a host endoglycosidase, when up-regulated by HSV-1 infection dictates local inflammatory response by destabilizing tissue architecture. Here, we demonstrate that HSV-1 reinfection in mice causes notable pathophysiology in wild-type controls compared to the animals lacking HPSE. The endoglycosidase promotes infected cell survival and supports a pro-disease environment. In contrast, lack of HPSE strengthens intrinsic immunity by promoting cytokine expression, inducing necroptosis of infected cells, and decreasing leukocyte infiltration into the cornea. Collectively, we report that immunity from a recent prior infection fails to abolish disease manifestation during HSV-1 reinfection unless HPSE is rendered inactive.

Larvicidal activity of silver nanoparticles synthesized using Pergularia daemia plant latex against Aedes aegypti and Anopheles stephensi and nontarget fish Poecillia reticulata.

In present study, the bioactivity of latex-producing plant Pergularia daemia as well as synthesized silver nanoparticles (AgNPs) against the larval instars of Aedes aegypti and Anopheles stephensi mosquito larvae was determined. The range of concentrations of plant latex (1,000, 500, 250, 125, 62.25, and 31.25 ppm) and AgNPs (10, 5, 2.5, 1.25, 0.625, and 0.3125 ppm) were prepared. The LC(50) and LC(90) values for first, second, third, and fourth instars of synthesized AgNPs-treated first, second, third, and fourth instars of A. aegypti (LC(50) = 4.39, 5.12, 5.66, 6.18; LC(90) = 9.90, 11.13, 12.40, 12.95 ppm) and A. stephensi (LC(50) = 4.41, 5.35, 5.91, 6.47; LC(90) = 10.10, 12.04, 13.05, 14.08 ppm) were found many fold lower than crude latex-treated A. aegypti (LC(50) = 55.13, 58.81, 75.66, 94.31; LC(90) = 113.00, 118.25, 156.95, 175.71 ppm) and A. stephensi (LC(50) = 81.47, 92.09, 96.07, 101.31; LC(90) = 159.51, 175.97, 180.67, 190.42 ppm). The AgNPs did not exhibit any noticeable effects on Poecillia reticulata after either 24 or 48 h of exposure at their LC(50) and LC(90) values against fourth-instar larvae of A. aegypti and A. stephensi. The UV-visible analysis shows absorbance for AgNPs at 520 nm. TEM reveals spherical shape of synthesized AgNPs. Particle size analysis revealed that the size of particles ranges from 44 to 255 nm with average size of 123.50 nm. AgNPs were clearly negatively charged (zeta potential -27.4 mV). This is the first report on mosquito larvicidal activity P. daemia-synthesized AgNPs.

Larvicidal activity of silver nanoparticles synthesized using Plumeria rubra plant latex against Aedes aegypti and Anopheles stephensi.

In the present study activity of silver nanoparticles (AgNPs) synthesized using Plumeria rubra plant latex against second and fourth larval instar of Aedes aegypti and Anopheles stephensi was determined. Range of concentrations of synthesized AgNps (10, 5, 2.5, 1.25, 0.625, 0.3125 ppm) and aqueous crude latex (1,000, 500, 250, 125, 62.50, 31.25 ppm) were tested against larvae of A. aegypti and A. Stephensi. The synthesized AgNps from P. rubra latex were highly toxic than crude latex extract in both mosquito species. The LC(50) values for second and fourth larval instars after 24 h of crude latex exposure were 1.49, 1.82 ppm against A. aegypti and 1.10, 1.74 ppm against A. stephensi respectively. These figures were 181.67, 287.49 ppm against A. aegypti and 143.69, 170.58 ppm against A. stephensi respectively for crude latex extract. The mortality rates were positively correlated with the concentration of AgNPs. The characterization studies of synthesized AgNPs by UV-Vis spectrophotometry, transmission electron microscopy (TEM), Particle size analysis (PSA) and zeta potential confirmed the spherical shape and size (32-200 nm) of silver nanoparticles along with stability. Toxicity studies carried out against non-target fish species Poecilia reticulata, the most common organism in the habitats of A. aegypti and A. stephensi showed no toxicity at LC(50) and LC(90) doses of the AgNPs. This is the first report on mosquito larvicidal activity of latex synthesized nanoparticles.

Insecticidal potency of bacterial species Bacillus thuringiensis SV2 and Serratia nematodiphila SV6 against larvae of mosquito species Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus.

The tremendous worldwide efforts to isolate novel mosquito larvicidal bacteria with improved efficacy present significant promise to control vector-borne diseases of public health importance. In the present study, two native bacterial isolates, Bacillus thuringiensis (Bt SV2) and Serratia species (SV6) were evaluated for mosquito larvicidal potential against the early fourth instar larvae of Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus with reference to B. thuringiensis subsp. israelensis (Bti) H 14. The native Gram-positive, spore-forming Bt SV2 isolate showed 100% mortality against early fourth instars of Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus, in parallel to Bti H14 strain. After 24 h, Bt SV2 showed 98%, 89%, and 80.67%, and Bti H14 showed 92%, 98.33%, and 60% mortality against Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus, respectively. Serratia SV6 showed highest activity against Culex quinquefasciatus (100%) followed by Anopheles stephensi (95%) and Aedes aegypti (91%) after 48 h of exposure. The Gram-negative Serratia SV6 showed delayed toxicity compared to Bti H14 and Bt SV2 against early fourth instars of Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus. The relative mortality of all treatments after 12-h exposures showed the varied toxicity with respect to exposure time, bacterial treatment, and mosquito species. Genetic relatedness of the strains was confirmed on the basis of phylogenetic reconstructions based on alignment of 16S rRNA gene sequences which indicated a strong clustering of the strain SV2 with B. thuringiensis and the strain SV6 with Serratia nematodiphila. In conclusion, the native isolate B. thuringiensis SV2 showed significant toxicity while Serratia SV6 showed less and delayed toxicity against several mosquito species compared with BtiH14. They may be used as novel bacterial insecticidal agents in mosquito vector-borne disease control. To our knowledge, this is the first report on mosquito larvicidal potential of Serratia species.

OPTN (optineurin)-mediated selective autophagy prevents neurodegeneration due to herpesvirus infection.

Very little is known about the mechanisms that restrict neurotropic herpesviruses such as herpes simplex virus-1 (HSV-1) from infecting the central nervous system (CNS) and causing widespread death of neurons. Likewise, HSV-1 is thought to play a role in chronic neurodegeneration, yet a direct association has remained elusive. To address these issues, we recently showed that the selective macroautophagy/autophagy receptor OPTN (optineurin) specifically targets HSV-1 proteins VP16 and gB for degradation to prevent viral spread in the brain. OPTN deficiency alters host cytokine expression and tissue-specific immune signaling, and enhances necroptotic death of infected neurons. HSV-1-infected optn knockout mice show higher susceptibility to lethal CNS infection and the surviving animals demonstrate cognitive deficiency. Our research suggests that OPTN-mediated autophagy provides an intrinsic immune barrier against neurotropic viruses and protects the CNS from neurodegenerative stress.

STAND alert! Prokaryotic immunity for recognition and defense against bacteriophages.

In a recent article, Gao et al. diversify our knowledge of prokaryotic innate immunity by characterizing a novel bacterial defense system that utilizes nucleotide-binding oligomerization-like receptors (NLRs) for recognizing phage proteins.

Postinfection Metabolic Reprogramming of the Murine Trigeminal Ganglion Limits Herpes Simplex Virus-1 Replication.

Herpes simplex virus type-1 (HSV-1) infections are known to alter the host metabolism for efficient propagation in vitro. However, in vivo metabolic perturbations upon prolonged HSV-1 infection remain poorly understood. We used high-resolution liquid chromatography coupled with mass spectrometry (LC-MS) and functional assays to determine the state of the trigeminal ganglion (TG) tissue metabolism upon prolonged corneal HSV-1 infection in a murine model. The metabolomics data indicated significant alterations in the host metabolic profile. After HSV-1 infection, the TG microenvironment assumed downregulation of central carbon metabolism and nucleotide synthesis pathways. We validated our observations using in vitro and ex vivo models through targeted inhibition of crucial metabolic polyamine pathways identified in our metabolomics screen. Our findings collectively suggested that HSV-1 infection altered the host metabolic product regulations that limit the energy and macromolecular precursors required for viral replication. IMPORTANCE The more severe ocular pathologies associated with HSV-1 infection are significant vision loss, ocular morbidity, and herpetic keratitis. The current clinical landscape lacks curative drugs and vaccines against HSV-1, a heavy burden associated with this neurotropic, ubiquitous pathogen. The virus is notoriously successful in establishing latency in the host TG, where it remains dormant with periodic reactivations in response to various stimuli like stress and immunosuppression. Metabolic perturbations in tissue microenvironment likely aid the virus in establishing its latent state along with subsequent reactivations yet remain poorly characterized. Here, we used mass spectrometry coupled with statistical data analysis to study the host metabolome in the TG during HSV-1 infection and identify metabolites that likely regulate infection.

Putative targeting by BX795 causes decrease in protein kinase C protein levels and inhibition of HSV1 infection.

Herpes simplex virus type-1 (HSV1) exploits cellular machinery for its own replicative advantage. Current treatment modalities against HSV1 cause toxicity and drug resistance issues. In the search for alternative forms of treatment, we have uncovered a small molecule, BX795, as a candidate drug with strong antiviral potential owing to its multitargeted mode of action. In this study, we show that in addition to a previously known mechanism of action, BX795 can directly interact with the proviral host factor protein kinase C (PKC) in silico. When administered to HSV1 or mock infected human corneal epithelial (HCE) cells, BX795 significantly reduces the protein level and perinuclear localization of proviral PKC-α and PKC-ζ isoforms. This activity closely mimics that of a known PKC inhibitor, Bisindolylmaleimide I (BIM I), which also inhibits viral replication. Taken together our studies demonstrate a previously unknown mechanism by which BX795 exerts its antiviral potential.

Prodigiosin produced by Serratia marcescens NMCC46 as a mosquito larvicidal agent against Aedes aegypti and Anopheles stephensi.

Microbial control agents offer alternatives to chemical pest control as they can be more selective than chemical insecticides. The present study evaluates the mosquito larvicidal potential of microbial pigment prodigiosin produced by Serratia marcescens NMCC46 against Aedes aegypti and Anopheles stephensi. The pigment of S. marcescens NMCC46 was extracted after 24 h from mannitol containing nutrient broth media. The effects of crude extracted pigment on the growth, survival, development, and other life cycle aspects were studied. The LC(50) and LC(90) values of second, third, and fourth instars of A. aegypti (LC(50) = 41.65, 139.51, 103.95; LC(90) = 117.81, 213.68, 367.82) and A. stephensi (LC(50) = 51.12, 105.52, 133.07; LC(90) = 134.81, 204.45, 285.35) were determined. At higher concentration (500 ppm), mortality starts within first 6 h of exposure. More than 50% mortality occurs within the first 24 h. The overall observed effects against A. aegypti and A. stephensi larvae after 48 h were increasing percent survival larvae, survival pupation, adult emergence with decreasing crude pigment extract concentration. These ensure that the resultant mosquito population reduction is substantial even where the larvicidal potential is minimal. The UV (λ (max) = 536 nm), TLC (Rf = 0.9), HPLC, and FTIR analysis of crude pigment shows the presence of prodigiosin as active compound. Thus, the active compound produced by this species would be more useful against vectors responsible for diseases of public health importance. This is the first report on mosquito larvicidal activity of prodigiosin produced by Serratia species.

Larvicidal potential of silver nanoparticles synthesized using fungus Cochliobolus lunatus against Aedes aegypti (Linnaeus, 1762) and Anopheles stephensi Liston (Diptera; Culicidae).

Larvicides play a vital role in controlling mosquitoes in their breeding sites. The present study was carried out to establish the larvicidal activities of mycosynthesized silver nanoparticles (AgNPs) against vectors: Aedes aegypti and Anopheles stephensi responsible for diseases of public health importance. The AgNPs synthesized by filamentous fungus Cochliobolus lunatus, characterized by UV-Vis spectrophotometry, Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. The characterization studies confirmed the spherical shape and size (3-21 nm) of silver nanoparticles. The efficacy of mycosynthesized AgNPs at all the tested concentrations (10, 5, 2.5, 1.25, 0.625, and 0.3125 ppm) against second, third, and fourth instar larvae of A. aegypti (LC(50) 1.29, 1.48, and 1.58; LC(90) 3.08, 3.33, and 3.41 ppm) and against A. stephensi (LC(50) 1.17, 1.30, and 1.41; LC(90) 2.99, 3.13, and 3.29 ppm) were observed, respectively. The mortality rates were positively correlated with the concentration of AgNPs. Significant (P < 0.05) changes in the larval mortality was also recorded between the period of exposure against fourth instar larvae of A. aegypti and A. stephensi. The possible larvicidal activity may be due to penetration of nanoparticles through membrane. Toxicity studies carried out against non-target fish species Poecilia reticulata, the most common organism in the habitats of A. aegypti and A. stephensi showed no toxicity at LC50 and LC90 doses of the AgNPs. This is the first report on mosquito larvicidal activity of mycosynthesized nanoparticles. Thus, the use of fungus C. lunatus to synthesize silver nanoparticles is a rapid, eco-friendly, and a single-step approach and the AgNps formed can be potential mosquito larvicidal agents.