Nitrogen and phosphorus eutrophication enhance biofilm-related drug resistance in Enterococcus faecalis isolated from Water Sources.

Antibiotic resistance is a critical topic worldwide with important consequences for public health. So considering the rising issue of antibiotic-resistance in bacteria, we explored the impact of nitrogen and phosphorus eutrophication on drug resistance mechanisms in Enterococcus faecalis, especially ciprofloxacin, oxytetracycline, and ampicillin. For this purpose we examined the antibiotic-resistance genes and biofilm formation of Enterococcus faecalis under different concentration of nitrogen and phosphorus along with mentioned antibiotics. Mesocosms were designed to evaluate the impact of influence of eutrophication on the underlying mechanism of drugn resistence in Enterococcus faecalis. For this purpose, we explored the potential relation to biofilm formation, adhesion ability, and the expression levels of the regulatory gene fsrA and the downstream gene gelEI. Our results demonstrated that the isolates of all treatments displayed high biofilm forming potential, and fsrA and gelE genes expression. Additionally, the experimental group demonstrated substantially elevated Enterococcus faecalis gelE expression. Crystal violet staining was applied to observe biofilm formation during bacterial development phase and found higher biofilm formation. In conclusion, our data suggest that E. faecalis resistance to ciprofloxacin, oxytetracycline, and ampicillin is related to biofilm development. Also, the high level of resistance in Enterococcus faecalis is linked to the expression of the fsrA and gelE genes. Understanding these pathways is vital in tackling the rising problem of bacterial resistance and its potential effect on human health.

Anti-influenza drug screening and inhibition of apigetrin on influenza A virus replication via TLR4 and autophagy pathways.

Activation of Toll-like receptor (TLR) 4 plays important roles in the influenzaA virus (IAV) infection. To explore TLR4 inhibitors, 161 traditional Chinese medicines (TCMs) were screened. Further, we screened out Ixeris sonchifolia Hance, and its active compound, Apigetrin (apigenin-7-O-glucoside). Antiviral activity of Apigetrin was determined by plaque assay. We also further investigated the influence of Apigetrin on immune signaling pathways including TLRs, MAPK, NF-κB and autophagy pathways. The in-vitro results showed that the extract and its several ingredients could significantly inhibit IAV replication. Apigetrin significantly improved IAV-induced oxidative stress, inhibited the IAV-induced cytokine storm by suppressing the excessive activation of TLR3/4/7, JNK/p38 MAPK and NF-κB. Apigetrin decreased autophagosome accumulation and promoted degradation of IAV protein. Interestingly, Apigetrin antiviral activity was reversed by using H2O2 and the agonists of TLR4, JNK/p38, NF-κB and autophagy. Most important, the in-vitro effective concentration is higher than the reported plasma concentration. The in-vivo test showed that Apigetrin significantly increased the average survival time, reduced the lung edema and IAV replication. In conclusion, we have found that Ixeris sonchifolia Hance and its several ingredients can inhibit IAV infection, and the mechanisms of action of Apigetrin against IAV is by regulating TLR4 and autophagy signaling pathways.

Gut microbiota assemblages of generalist predators are driven by local- and landscape-scale factors.

The gut microbiomes of arthropods have significant impact on key physiological functions such as nutrition, reproduction, behavior, and health. Spiders are diverse and numerically dominant predators in crop fields where they are potentially important regulators of pests. Harnessing spiders to control agricultural pests is likely to be supported by an understanding of their gut microbiomes, and the environmental drivers shaping microbiome assemblages. This study aimed to deciphering the gut microbiome assembly of these invertebrate predators and elucidating potential implications of key environmental constraints in this process. Here, we used high-throughput sequencing to examine for the first time how the assemblages of bacteria in the gut of spiders are shaped by environmental variables. Local drivers of microbiome composition were globally-relevant input use system (organic production vs. conventional practice), and crop identity (Chinese cabbage vs. cauliflower). Landscape-scale factors, proportion of forest and grassland, compositional diversity, and habitat edge density, also strongly affected gut microbiota. Specific bacterial taxa were enriched in gut of spiders sampled from different settings and seasons. These findings provide a comprehensive insight into composition and plasticity of spider gut microbiota. Understanding the temporal responses of specific microbiota could lead to innovative strategies development for boosting biological control services of predators.

Antibiotic nitrofurazone drives the functional dynamics of periphytic protozoan fauna in marine environments.

The use of functional traits of a community as a method to measure its functional dynamics in response to environmental change has gained attention because trait-based approaches offer systematic opportunities to understand the interactions between species diversity and ecosystem function. However, the relationship between functional traits of periphytic protozoa and contamination of aquatic habitats with antibiotics is poorly understood. In this study, we investigated the influence of the antibiotic nitrofurazone on functional traits of marine periphytic protozoan fauna. For this purpose, the protozoan assemblages were collected from coastal waters of the Yellow Sea at Qingdao, northern China, during four seasons of a one-year cycle using glass microscope slides as artificial substrates. The test protozoan communities were then exposed to various treatments of nitrofurazone in laboratory bioassay experiments. Our results demonstrated that the modalities of the functional traits of protozoan communities were generally driven by nitrofurazone toxicity. Briefly, R-mode linked to Q-mode (RLQ) and fourth-corner analyses revealed strong positive correlations between functional traits and nitrofurazone treatments. Trait syndromes in terms of body length, width, weight, height, and size to volume ratios were significantly influenced by nitrofurazone exposure. In particular, small and medium body size species of different feeding types, i.e., algivores, bacterivores, raptors or non-selectives, were more sensitive than other protozoan species to higher concentrations of nitrofurazone. Our findings demonstrate that antibiotic toxicity is likely to affect periphytic protozoan community function, shape the functional processes, and induce toxic responses in the community. The findings of this study suggest that periphytic protozoan communities and their functional traits are suitable bioindicators for evaluating the ecotoxicity of nitrofurazone in marine environments.

Human circulating bacteria and dysbiosis in non-infectious diseases.

Blood microorganisms were once thought to indicate infection. Blood in healthy people appears to be devoid of growing bacteria; nonetheless, intracellular dormant forms of bacteria have been reported previously. With breakthroughs in sequencing and bioinformatics, the presence of bacterial DNA in healthy human blood initiated the controversy of human blood microbiota (HBM). Recently, bacteria-specific DNA and culturable bacteria were found in healthy human blood. Researchers wanted to study the phenomena of a "healthy blood microbiota" by providing a thorough description of bacterially produced nucleic acids using many complementing molecular and traditional microbiological approaches. Because blood is a relatively limited and particular environment, culturability and plate count issues can be overcome using enhanced cultured procedures. However, more evidence is required to confirm that healthy human blood contains normal microbiota. Cavities, mouth and intestinal microbiota, trauma, surgery, and animal/insect bites can introduce bacteria into human blood. All these factors strengthen the concept of transient blood bacteria too. The presence of blood bacteria may be caused by temporary immunological clearance and absorption by dendritic or M cells. This review provides an extensive and comprehensive analysis that suggests that healthy blood bacteria may not be typical microbiota but transient circulatory microorganisms. In this study, we look at how contaminants (Escherichia, Shigella, Pseudomonads, etc.) from the skin, laboratory environments, and reagents can affect the interpretation of blood-derived microbial information and the relationship between the circulating bacteria and non-communicable diseases. Circulating transient bacteria may play a role in the pathogenesis of non-infectious diseases such as diabetes and CVD. Contamination-free hematological studies can aid in understanding the disease mechanisms, therapy, and biomarkers.

Type I IFNs: A Blessing in Disguise or Partner in Crime in MERS-CoV-, SARS-CoV-, and SARS-CoV-2-Induced Pathology and Potential Use of Type I IFNs in Synergism with IFN-γ as a Novel Antiviral Approach Against COVID-19.

Since the end of 2019, the emergence of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has accelerated the research on host immune responses toward the coronaviruses. When there is no approved drug or vaccine to use against these culprits, host immunity is the major strategy to fight such infections. Type I interferons are an integral part of the host innate immune system and define one of the first lines of innate immune defense against viral infections. The in vitro antiviral role of type I IFNs against Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV (severe acute respiratory syndrome coronavirus) is well established. Moreover, the involvement of type I IFNs in disease pathology has also been reported. In this study, we have reviewed the protective and the immunopathogenic role of type I IFNs in the pathogenesis of MERS-CoV, SARS-CoV, and SARS-CoV-2. This review will also enlighten the potential implications of type I IFNs for the treatment of COVID-19 when used in combination with IFN-γ.

Zinc Finger CCCH-Type Antiviral Protein 1 Restricts the Viral Replication by Positively Regulating Type I Interferon Response.

Zinc finger CCCH-type antiviral protein 1 (ZC3HAV1) is a host antiviral factor that can repress translation and promote degradation of specific viral mRNAs. In this study, we found that expression of ZC3HAV1 was significantly induced by infection with influenza A virus (IAV) and Sendai virus (Sev). It was shown that deficiency of IFNAR resulted in a dramatic decrease in the virus-induced expression of ZC3HAV1. Furthermore, transfection with poly(I:C) and treatment with interferon ß (IFN-ß) induced the ZC3HAV1 expression. Interference with the endogenous expression of ZC3HAV1 enhanced the replication of influenza virus by impairing the production of IFN-ß and MxA, following the infection of influenza virus. In contrast, ectopic expression of ZC3HAV1 significantly restricted the replication of influenza virus by increasing the IFN-ß expression. In addition, ZC3HAV1 also promoted the induction of tumor necrosis factor and interleukin 6. These results suggest that ZC3HAV1 is induced by IFN-ß/IFNAR signaling during IAV and Sev infection and involved in positive regulation of IFN-dependent innate antiviral response.

Anti-chicken type I IFN countermeasures by major avian RNA viruses.

Chicken type I interferons (type I IFNs) are key antiviral players of the chicken innate immune system and are considered potent antiviral agents against avian viral pathogens. Chicken type I IFNs are divided into three subtypes namely, chIFN-α, chIFN-ß, and chIFN-κ. Viral pathogen-associated molecular patterns (PAMPs) recognized by their corresponding specific PRRs (pattern recognition receptors) induce the expression of chicken type I IFNs. Interaction of chicken type I IFNs with their subsequent IFN receptors results in the activation of the JAK-STAT pathway, which in turn activates hundreds of chicken interferon-stimulated genes (chISGs). These chISGs establish an antiviral state in neighboring cells and prevent the replication and dissemination of viruses within chicken cells. Chicken type I IFNs activate different pathways that constitute major antiviral innate defense mechanisms in chickens. However, evolutionary mechanisms in viruses have made them resistant to these antiviral players by manipulating host innate immune pathways. This review focuses on the underlying molecular mechanisms employed by avian RNA viruses to counteract chicken type I IFNs and chISGs through different viral proteins. This may help to understand host-pathogen interactions and the development of novel therapeutic strategies to control viral infections in poultry.

Web of interferon stimulated antiviral factors to control the influenza A viruses replication.

Influenza viruses cause mild to severe infections in animals and humans worldwide with significant morbidity and mortality. Infection of eukaryotic cells with influenza A viruses triggers the induction of innate immune system through the interaction between pattern recognition receptors (PRRs) and pathogen associated molecular patterns (PAMPs), which culminate in the induction of interferons (IFNs). Consequently, IFNs bind to their cognate receptors on the cellular membrane and activate the signaling pathway for transcriptional regulation of interferon-stimulated genes (ISGs) through Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. Cumulative actions of these ISGs establish an antiviral state of the host. Several ISGs have been described, which play critical roles to inhibit the infection and replication of influenza A viruses at multiple steps of virus life cycle. In this review, the dynamics and redundancy of these ISGs against influenza A viruses are discussed. Additionally, current understanding and molecular mechanisms that are underlying the roles of ISGs in pathogenesis of influenza virus are critically reviewed.

Functional Involvement of Interferon-Inducible Transmembrane Proteins in Antiviral Immunity.

Interferons (IFNs) play crucial roles in host defense against viral infections by inducing the expression of numerous IFN-stimulated genes (ISGs) that can activate host antiviral immunity. Interferon-inducible transmembrane proteins (IFITMs), a family of small transmembrane proteins, are critical ISG products. Compelling evidence has implicated that IFITMs can establish an innate immune state to eliminate pathogens efficiently. IFITM proteins can impede broad-spectrum viral infection through various mechanisms. It is generally believed that IFITMs can block the viral entry by suppressing viral membrane fusion. However, some findings indicated that IFITMs might also inhibit viral gene expression and viral protein synthesis and thereby impair viral replication. IFITMs may incorporate into virions during viral assembly and thus reduce the infectivity of nascent virions. The precise inhibitory mechanism of IFITMs on viral infection and replication still requires further exploration. In this review, we highlight the recent findings regarding critical roles of IFITMs in host-virus interaction. We also discuss the molecular mechanisms underlying their functions in antiviral responses.

Immune Ecosystem of Virus-Infected Host Tissues.

Virus infected host cells serve as a central immune ecological niche during viral infection and replication and stimulate the host immune response via molecular signaling. The viral infection and multiplication process involves complex intracellular molecular interactions between viral components and the host factors. Various types of host cells are also involved to modulate immune factors in delicate and dynamic equilibrium to maintain a balanced immune ecosystem in an infected host tissue. Antiviral host arsenals are equipped to combat or eliminate viral invasion. However, viruses have evolved with strategies to counter against antiviral immunity or hijack cellular machinery to survive inside host tissue for their multiplication. However, host immune systems have also evolved to neutralize the infection; which, in turn, either clears the virus from the infected host or causes immune-mediated host tissue injury. A complex relationship between viral pathogenesis and host antiviral defense could define the immune ecosystem of virus-infected host tissues. Understanding of the molecular mechanism underlying this ecosystem would uncover strategies to modulate host immune function for antiviral therapeutics. This review presents past and present updates of immune-ecological components of virus infected host tissue and explains how viruses subvert the host immune surveillances.

Role of innate immunity in pathophysiology of classical swine fever virus infection.

Classical swine fever virus (CSFV) infection causes mild to severe diseases among pigs, depending on the age and immune status of the host and viral strains. CSFV targets various cells, including macrophages and conventional and plasmacytoid dendritic cells. Classical swine fever is one of the most devastating diseases of pigs which leads to high morbidity and mortality, and causes significant economic loss worldwide. In response to infection with CSFV, host innate immune system eliminates the virus by recognizing specific viral molecules via distinct cellular pattern recognition receptors. These receptors trigger downstream intracellular signaling pathways, which regulate the translocation and activation of transcription factors that control the production of cytokines and interferons (IFNs). In turn, these IFNs activate JAK-STAT signaling that governs the transcription of IFN-stimulated genes (ISGs) that play critical roles in antiviral immunity. However, CSFV has evolved different strategies to evade innate immune signaling and can establish persistent infection without being recognized by immune surveillance. In this review, we discuss the current understanding of host innate response to CSFV infection. We also summarize how CSFV evades innate immunity to establish its chronic infection.

Host Immune Response to Influenza A Virus Infection.

Influenza A viruses (IAVs) are contagious pathogens responsible for severe respiratory infection in humans and animals worldwide. Upon detection of IAV infection, host immune system aims to defend against and clear the viral infection. Innate immune system is comprised of physical barriers (mucus and collectins), various phagocytic cells, group of cytokines, interferons (IFNs), and IFN-stimulated genes, which provide first line of defense against IAV infection. The adaptive immunity is mediated by B cells and T cells, characterized with antigen-specific memory cells, capturing and neutralizing the pathogen. The humoral immune response functions through hemagglutinin-specific circulating antibodies to neutralize IAV. In addition, antibodies can bind to the surface of infected cells and induce antibody-dependent cell-mediated cytotoxicity or complement activation. Although there are neutralizing antibodies against the virus, cellular immunity also plays a crucial role in the fight against IAVs. On the other hand, IAVs have developed multiple strategies to escape from host immune surveillance for successful replication. In this review, we discuss how immune system, especially innate immune system and critical molecules are involved in the antiviral defense against IAVs. In addition, we highlight how IAVs antagonize different immune responses to achieve a successful infection.

Evolution of Influenza A Virus by Mutation and Re-Assortment.

Influenza A virus (IAV), a highly infectious respiratory pathogen, has continued to be a significant threat to global public health. To complete their life cycle, influenza viruses have evolved multiple strategies to interact with a host. A large number of studies have revealed that the evolution of influenza A virus is mainly mediated through the mutation of the virus itself and the re-assortment of viral genomes derived from various strains. The evolution of influenza A virus through these mechanisms causes worldwide annual epidemics and occasional pandemics. Importantly, influenza A virus can evolve from an animal infected pathogen to a human infected pathogen. The highly pathogenic influenza virus has resulted in stupendous economic losses due to its morbidity and mortality both in human and animals. Influenza viruses fall into a category of viruses that can cause zoonotic infection with stable adaptation to human, leading to sustained horizontal transmission. The rapid mutations of influenza A virus result in the loss of vaccine optimal efficacy, and challenge the complete eradication of the virus. In this review, we highlight the current understanding of influenza A virus evolution caused by the mutation and re-assortment of viral genomes. In addition, we discuss the specific mechanisms by which the virus evolves.

Molecular Mechanism of Quorum-Sensing in Enterococcus faecalis: Its Role in Virulence and Therapeutic Approaches.

Quorum-sensing systems control major virulence determinants in Enterococcusfaecalis, which causes nosocomial infections. The E. faecalis quorum-sensing systems include several virulence factors that are regulated by the cytolysin operon, which encodes the cytolysin toxin. In addition, the E. faecalis Fsr regulator system controls the expression of gelatinase, serine protease, and enterocin O16. The cytolysin and Fsr virulence factor systems are linked to enterococcal diseases that affect the health of humans and other host models. Therefore, there is substantial interest in understanding and targeting these regulatory pathways to develop novel therapies for enterococcal infection control. Quorum-sensing inhibitors could be potential therapeutic agents for attenuating the pathogenic effects of E. faecalis. Here, we discuss the regulation of cytolysin, the LuxS system, and the Fsr system, their role in E. faecalis-mediated infections, and possible therapeutic approaches to prevent E. faecalis infection.

Avian Tembusu virus infection effectively triggers host innate immune response through MDA5 and TLR3-dependent signaling pathways.

Avian Tembusu virus (ATMUV) is a newly emerged flavivirus that belongs to the Ntaya virus group. ATMUV is a highly pathogenic virus causing significant economic loss to the Chinese poultry industry. However, little is known about the role of host innate immune mechanism in defending against ATMUV infection. In this study, we found that ATMUV infection significantly up-regulated the expression of type I and type III interferons (IFN) and some critical IFN-stimulated genes (ISG) in vivo and in vitro. This innate immune response was induced by genomic RNA of ATMUV. Furthermore, we observed that ATMUV infection triggered IFN response mainly through MDA5 and TLR3-dependent signaling pathways. Strikingly, shRNA-based disruption of IPS-1, IRF3 or IRF7 expression significantly reduced the production of IFN in the 293T cell model. Moreover, NF-κB was shown to be activated in both chicken and human cells during the ATMUV infection. Inhibition of NF-κB signaling also resulted in a clear decrease in expression of IFN. Importantly, experiments revealed that treatment with IFN significantly impaired ATMUV replication in the chicken cell. Consistently, type I IFN also exhibited promising antiviral activity against ATMUV replication in the human cell. Together, these data indicate that ATMUV infection triggers host innate immune response through MDA5 and TLR3-dependent signaling that controls IFN production, and thereby induces an effective antiviral immunity.

Survey of coccidial infection of rabbits in Sichuan Province, Southwest China.

Coccidiosis is a challenging disease of wild and domestic rabbits both, caused by Eimeria and thereby leads enormous economic losses at rabbit farms. The present study carried out to survey the prevalence and intensity of coccidial infection among the rabbits in Sichuan Province, southwest China. A total of 110 faecal samples were collected from 11 farms situated in eight main rabbits rearing administrative regions. Oocysts in faecal samples were purified, sporulated and identified according to morphological features. The overall prevalence of infection was 56.4 % (62/110), with prevalence of 64 % (47/75) for local meat breeds of rabbit and 51.4 % (18/35) for Rex Rabbits (local fur rabbits). Weanling rabbits had the highest prevalence (74 %, 37/50), followed by young rabbits (45 %, 13/29) and the adult rabbits showed the lowest prevalence (42 %, 13/31). Concurrent infection with two to seven Eimeria species was found. In total, 9 species of Eimeria were identified from oocyst-positive samples. E. perforans was the most prevalent specie (42.73 %), followed in order by Eimiera media, E. irresidua, E. magna, and E. intestinalis with prevalences of 35.45, 34.55, 31.82, and 23.64 %, respectively. Results of the present investigation indicated that the prevalence of coccidial infection is high among the rabbit population in southwest China. This study also elucidate about the coccidial infection and emphasis to adopt control strategies in commercial rabbitories.

Induction of innate immunity and its perturbation by influenza viruses.

Influenza A viruses (IAV) are highly contagious pathogens causing dreadful losses to human and animal, around the globe. IAVs first interact with the host through epithelial cells, and the viral RNA containing a 5'-triphosphate group is thought to be the critical trigger for activation of effective innate immunity via pattern recognition receptors-dependent signaling pathways. These induced immune responses establish the antiviral state of the host for effective suppression of viral replication and enhancing viral clearance. However, IAVs have evolved a variety of mechanisms by which they can invade host cells, circumvent the host immune responses, and use the machineries of host cells to synthesize and transport their own components, which help them to establish a successful infection and replication. In this review, we will highlight the molecular mechanisms of how IAV infection stimulates the host innate immune system and strategies by which IAV evades host responses.

Isolation of buffalo poxvirus from clinical case and variations in the genetics of the B5R gene over fifty passages.

Outbreaks of buffalopox affect udder and teats, which may ultimately lead to mastitis in dairy buffalo and can significantly compromise the production. In this study, we report isolation of buffalo poxvirus and sequence analysis of the B5R gene collected from the buffalo clinically suspected to be poxvirus infected. The virus was isolated on BHK-21 cell line and was passaged for 50 times, B5R gene was amplified and sequenced using gene-specific primers, and analyzed at both nucleotide and amino acid levels. Phylogenetically, the isolate can be classified close to the previously reported Pakistani and Indian isolates with certain level of differential clustering patterns. Three significant putative mutations (I2K, N64D, and K111E) were observed in the B5R protein. The K111E was common with previous human isolate from Karachi, Pakistan in 2005. These mutations differed from poxviruses reported from the neighboring countries. Some deletion mutations were observed which were recovered in upcoming passages. The K111E mutation suggests potential to cause zoonotic infection in human all over the country.