Evasion of complement-mediated supplement and lysis C3 deposition are regulated by Francisella tularensis lipopolysaccharide O antigen. future study. Launch was first defined as the causative Ambroxol agent of the fatal plague-like disease within a inhabitants of surface squirrels in Tulare State, CA, in 1911 (147). Known as honoring Edward Francis Originally, who spent his profession extensively learning and characterizing the transmitting and growth of the bacterium (209). Though it causes disease in squirrels, rabbits, and many various other mammals, no pet has been defined as a tank. Instead, the reservoir could be or amoebae living therein freshwater. As there is absolutely no person-to-person spread, is certainly obtained by human beings via arthropod vectors or zoonotic transmitting mainly, though it is also sent by inhalation of aerosolized bacterias or ingestion of polluted food or drinking water (2). Inhalation of causes the most unfortunate infections, in support of 10 bacteria can result in a fatal disease potentially. This high infectivity, along Ambroxol using its simple aerosolization, have resulted in its background of weaponization (209). types are endemic just in the North Hemisphere. subsp. (types in THE UNITED STATES. subsp. (by serial passing. LVS causes an extremely mild infections in human beings but could cause a lethal infections in mice and it is therefore widely used being a model to review pathogenesis. The carefully related types causes disease in human beings seldom, though some situations have been noted (31, 125). Nevertheless, is certainly extremely virulent in mice, has over 98% identity to at the DNA level (188), shares many of the same virulence genes (43), and is also used as a model system to study virulence. Mouse monoclonal to LAMB1 Finally, subsp. is a species of intermediate virulence in humans and is found in Central Asia, while and can cause infections in aquatic organisms, including wild and farmed fish (57). Throughout this paper we will refer to subspecies are the etiological agents of the disease tularemia, also known as rabbit fever. Tularemia is characterized by a 3- to 5-day incubation period (209) Ambroxol during which the bacteria replicate almost silently in macrophages and other types of host cells. The eventual release of bacteria from these cells may coincide with the presentation of flu-like symptoms. There are several manifestations of tularemia, each dependent on the route of acquisition (159). The most common form of tularemia is ulceroglandular disease, which can result from insect bites or from contact with infected animal tissues following mechanical damage to the skin. A cutaneous ulcer develops at the site of infection, and bacteria drain to lymph nodes, subsequently causing a systemic infection. Less common forms of the disease include pneumonic, oculoglandular, and oropharyngeal tularemia. Streptomycin or doxycycline is indicated for treatment. Tularemia may be fatal; however, survivors gain robust immunity that has been found to last for up to 30 years (79). Upon infection, initially comes into contact with extracellular defenses such as complement, antibody, and cationic antimicrobial peptides (28, 29, 51, 190). Binding of these components to bacteria directly or indirectly leads to lysis and killing (189). Therefore, uses multiple surface structures and outer membrane modifications (capsule, lipopolysaccharide [LPS] O antigen, modifications that increase surface charge, etc.) to resist these components and block killing. In addition, this prevents structural damage that would release proinflammatory bacterial components capable of initiating a strong immune response. also enters host cells as an efficient way of evading extracellular defenses. After engulfment by phagocytic cells, including macrophages, is taken up into phagosomes that contain an array of toxic antimicrobials aimed at degrading the bacteria (Fig. 1). However, this pathogen has an equally diverse cache of defenses to counteract host antimicrobials. These once again prevent not only killing but also the release of proinflammatory bacterial components that could be recognized by host innate immune receptors (including Toll-like receptors [TLRs]) that stimulate inflammatory responses. Furthermore, similarly to entering host cells to avoid extracellular antimicrobials, escapes the phagosome to avoid phagosomal antimicrobials and, importantly, reach the cytosol, where it can replicate (Fig. 1). The cytosol is also, however, guarded by innate recognition and defense systems (including the inflammasome) with which the bacteria must contend. In order to replicate in this host compartment, must also obtain the nutrients required to sustain its rapid cell division and actively counteract host defenses aimed at limiting nutrient availability. Open in a separate window Fig 1 Stages of pathogenesis in the macrophage. can be detected by multiple macrophage receptors (see Mechanisms of Entry and Fate of Intracellular uses multiple mechanisms to evade host defenses in this harsh environment (inset). blocks the NADPH oxidase and also detoxifies reactive oxygen species (ROS). It can also resist the action of antimicrobial Ambroxol peptides.