Abstract: The continuously improving sophistication of molecular engineering techniques gives access to novel classes of bio-therapeutics and new challenges for their production in full respect of the strengthening regulations. Among these biologic agents are DNA based vaccines or gene therapy products and to a lesser extent genetically engineered live vaccines or delivery vehicles. The use of antibiotic-based selection, frequently associated with genetic manipulation of microorganism is currently undergoing a profound metamorphosis with the implementation and diversification of alternative selection means. This short review will present examples of alternatives to antibiotic selection and their context of application to highlight their ineluctable invasion of the bio-therapeutic world.
Abstract: This article summarizes current experimental knowledge on the efficacy, possible mechanisms and feasibility in the application of phytogenic products as feed additives for food-producing animals. Phytogenic compounds comprise a wide range of plant-derived natural bioactive compounds and essential oils are a major group. Numerous studies have demonstrated that phytogenic compounds have a variety of functions, including antimicrobial/antiviral, antioxidative and anti-inflammation effects and improvement in the palatability of feed and gut development/health. However, the mechanisms underlying their functions are still largely unclear. In the past, there has been a lack of consistency in the results from both laboratory and field studies, largely due to the varied composition of products, dosages, purities and growing conditions of animals used. The minimal inhibitory concentration (MIC) of phytogenic compounds required for controlling enteric pathogens may not guarantee the best feed intake, balanced immunity of animals and cost-effectiveness in animal production. The lipophilic nature of photogenic compounds also presents a challenge in effective delivery to the animal gut and this can partially be resolved by microencapsulation and combination with other compounds (synergistic effect). Interestingly, the effects of photogenic compounds on anti-inflammation, gut chemosensing and possible disruption of bacterial quorum sensing could explain a certain number of studies with different animal species for the better production performance of animals that have received phytogenic feed additives. It is obvious that phytogenic compounds have good potential as an alternative to antibiotics in feed for food animal production and the combination of different phytogenic compounds appears to be an approach to improve the efficacy and safety of phytogenic compounds in the application. It is our expectation that the recent development of high-throughput and “omics” technologies can significantly advance the studies on the mechanisms underlying phytogenic compounds’ functions and, therefore, guide the effective use of the compounds.
Abstract: The ability to form biofilms in a variety of environments is a common trait of bacteria, and may represent one of the earliest defenses against predation. Biofilms are multicellular communities usually held together by a polymeric matrix, ranging from capsular material to cell lysate. In a structure that imposes diffusion limits, environmental microgradients arise to which individual bacteria adapt their physiologies, resulting in the gamut of physiological diversity. Additionally, the proximity of cells within the biofilm creates the opportunity for coordinated behaviors through cell–cell communication using diffusible signals, the most well documented being quorum sensing. Biofilms form on abiotic or biotic surfaces, and because of that are associated with a large proportion of human infections. Biofilm formation imposes a limitation on the uses and design of ocular devices, such as intraocular lenses, posterior contact lenses, scleral buckles, conjunctival plugs, lacrimal intubation devices and orbital implants. In the absence of abiotic materials, biofilms have been observed on the capsule, and in the corneal stroma. As the evidence for the involvement of microbial biofilms in many ocular infections has become compelling, developing new strategies to prevent their formation or to eradicate them at the site of infection, has become a priority.
Abstract: Recent studies show that CD4+CD25+Foxp3+ regulatory cells (Tregs) produce effector cytokines under inflammatory conditions. However, the direct role of microbial agents that serve as toll-like receptor (TLR) ligands in the induction of effector cytokines in Tregs is less clear. Here we show that CD4+Foxp3+Tregs produce the effector cytokine IL-17A during oropharyngeal candidiasis (OPC) and inflammatory bowel disease in a TLR-2/Myd88 signaling dependent manner. TLR-2 ligands promote proliferation in Tregs in the presence and absence of TCR signals and inflammatory cytokines in vitro. The proliferation is directly dependent on TLR-2 expression in Tregs. Consistent with this, Tlr2−/− mice harbor fewer thymically derived Tregs and peripheral Tregs under homeostatic conditions in vivo. However, under Th17 inducing conditions, IL-6 and TLR-2 signaling both in Tregs as well as antigen presenting cells (APC) are critical for maximal ROR-γt and IL-17A up-regulation in Foxp3+ Tregs. The minimal and transient loss of Foxp3 expression and suppressive properties are due to the presence of IL-6 in the milieu, but not the direct effect of TLR-2 signaling in Tregs. Taken together, our data reveal that TLR-2 signaling promotes not only proliferation, but also IL-17A in Tregs, depending on the cytokine milieu. These IL-17A producing Tregs may be relevant in mucosal infections and inflammation.
Abstract: Chronic lung infections are associated with increased morbidity and mortality for individuals with underlying respiratory conditions such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). The process of chronic colonisation allows pathogens to adapt over time to cope with changing selection pressures, co-infecting species and antimicrobial therapies. These adaptations can occur due to environmental pressures in the lung such as inflammatory responses, hypoxia, nutrient deficiency, osmolarity, low pH and antibiotic therapies. Phenotypic adaptations in bacterial pathogens from acute to chronic infection include, but are not limited to, antibiotic resistance, exopolysaccharide production (mucoidy), loss in motility, formation of small colony variants, increased mutation rate, quorum sensing and altered production of virulence factors associated with chronic infection. The evolution of Pseudomonas aeruginosa during chronic lung infection has been widely studied. More recently, the adaptations that other chronically colonising respiratory pathogens, including Staphylococcus aureus, Burkholderia cepacia complex and Haemophilus influenzae undergo during chronic infection have also been investigated. This review aims to examine the adaptations utilised by different bacterial pathogens to aid in their evolution from acute to chronic pathogens of the immunocompromised lung including CF and COPD.
Abstract: Hepatitis delta virus (HDV) is a defective RNA virus that has an absolute requirement for a virus belonging to the hepadnaviridae family like hepatitis B virus (HBV) for its replication and formation of new virions. HDV infection is usually associated with a worsening of HBV-induced liver pathogenesis, which leads to more frequent cirrhosis, increased risk of hepatocellular carcinoma (HCC), and fulminant hepatitis. Importantly, no selective therapies are available for HDV infection. The mainstay of treatment for HDV infection is pegylated interferon alpha; however, response rates to this therapy are poor. A better knowledge of HDV–host cell interaction will help with the identification of novel therapeutic targets, which are urgently needed. Animal models like hepadnavirus-infected chimpanzees or the eastern woodchuck have been of great value for the characterization of HDV chronic infection. Recently, more practical animal models in which to perform a deeper study of host virus interactions and to evaluate new therapeutic strategies have been developed. Therefore, the main focus of this review is to discuss the current knowledge about HDV host interactions obtained from cell culture and animal models.