In humans, plague infection can manifest in one of three forms based on transmission route and tissues infected. Colonization of the lungs results in secondary pneumonic plague and the possibility of person to person transmission through aerosol droplets (main pneumonic plague). Plague contamination rapidly progresses and is associated with a high mortality rate in untreated individuals (70100%). Successful treatment of contamination is usually greatly increased with CZC-25146 hydrochloride early detection. Three plague pandemics have occurred, resulting in the death of over a third of the population of Europe and impacting the development of Western societies (Perry CZC-25146 hydrochloride and Fetherston,1997; Ligon,2006). While plague has been considered a historic disease, issues about the use ofY. pestisas a biological weapon and isolation of antibiotic resistantY. pestisstrains from nature have increased efforts to understand plague pathogenesis and develop novel therapeutics (Galimand et al.,1997; Inglesby et al.,2000). Experts are equipped with a variety of tools to dissect the virulence mechanisms ofY. pestisand develop new approaches to combat the CZC-25146 hydrochloride potential use of plague as a bioweapon. Here, we will discuss models of plague contamination, their potential for use in defining plague pathogenesis, and their importance in translational research. == Human Plague == Humans are considered accidental hosts forYersinia pestisand are extremely susceptible to contamination. Human plague can present in infected patients in three forms: bubonic, septicemic, and pneumonic. Bubonic plague, the most common form, occurs after transmission ofY. pestisfrom an infected flea. The incubation period for bubonic plague is usually 28 days after exposure. During this incubation period,Y. pestisdisseminates from your bite site to the regional lymph node. There the bacteria evade immune clearance and proliferate to high figures. Patients in the beginning present with flu-like symptoms, highlighted by the sudden onset of fever, chills, lethargy, and headache (Butler,1983; Dennis,2005; Adamovicz and Worsham,2006). As the bacteria continue to proliferate, patients develop extremely painful swollen lymph nodes called buboes. Eventually these tissues will contain enormous numbers of extracellular bacteria. Typically patients present with a single bubo at CD300E the draining lymph node of the bite site. Infected lymph nodes become severely damaged, and pathology is usually characterized by hemorrhage and necrosis (Flexner,1901). Without treatment, bubonic plague mortality rates approach 60%. However, bubonic plague responds well to antibiotic treatment, and mortality rates with proper treatment have decreased to below 5% (Dennis,2005). Bubonic plague can progress to septicemic plague if bacteria enter the blood stream. Septicemic plague is usually characterized by high bacteremia and is accompanied by a dangerous endotoxemia. In rare cases,Y. pestiscan directly infect the blood and cause septicemic plague without presenting with symptoms of bubonic plague (called main septicemic plague). Septicemic patients often have fever, severe headache, and lethargy but may also present with gatrointestinal symptoms (nausea, vomiting, diarrhea, and abdominal pain). Without the clinical development of buboes, septicemic patients are often not diagnosed with plague untilY. pestisis recognized in blood smears. By this time the prognosis for infected patients is usually poor, and mortality rates are high even with antibiotic treatment (Butler,1983). In a small percentage of bubonic patients,Y. pestiscan spread hematogenously to other tissues, including the lungs. Lung colonization can lead to the development of secondary pneumonic plague and the possibility of person to person transmission. Inhalation of aerosols containingY. pestiscan result in main pneumonic plague in naive individuals. Main pneumonic plague has a short incubation period of 12 days, followed by sudden onset of symptoms (fever, headache, chest pain, cough) and quick progression of contamination. Patients can present.