Abstract
Plague, caused by the bacterial pathogen Yersinia pestis, is a vector-borne disease that has caused millions of human deaths over several centuries. Presently, human plague infections continue throughout the world. Transmission from one host to another relies mainly on infected flea bites, which can cause enlarged lymph nodes called buboes, followed by septicemic dissemination of the pathogen. Additionally, droplet inhalation after close contact with infected mammals can result in primary pneumonic plague. Here, we review research advances in the areas of vaccines and therapeutics for plague in context of Y. pestis virulence factors and disease pathogenesis. Plague continues to be both a public health threat and a biodefense concern and we highlight research that is important for infection mitigation and disease treatment.
Highlights
Plague Prevention and Therapy: Yersinia pestis is a Gram-negative coccobacillus that is the etiologic agent of plague, an acute infectious disease that has played an important role in human history [1,2,3,4,5]
Y. pestis carries three plasmids, two of which are unique to this species: pMT1, which encodes the fraction 1 (F1) capsular antigen and pPCP, which carries the gene for the virulence factor plasminogen activator
Both F1 and V have been studied as components of subunit vaccines and have been shown to confer significant protection against bubonic and pneumonic plague induced by encapsulated strains of Y. pestis, with few documented concerns about tolerability or safety [155,157,162,163,164,165]
Summary
Plague Prevention and Therapy: Yersinia pestis is a Gram-negative coccobacillus that is the etiologic agent of plague, an acute infectious disease that has played an important role in human history [1,2,3,4,5]. Other susceptible species can be infected, causing an outbreak—this is referred to as epizootic plague In this disease cycle, animals become infected and die as fleas from infected natural reservoir species begin to seek other blood sources and the probability of human transmission is increased [11]. Y. pestis can cause three forms of plague disease: bubonic, septicemic, and pneumonic (Figure 1). Septicemic plague can result as a secondary issue arising from bubonic disease or if the bacteria are introduced directly to the blood stream (red). In other more severe cases, the bacteria can enter the blood stream directly and tiply, causing septicemic plague. The increased number of bacteria in the blood causes release of endotoxins, leading to ischemic necrosis In those cases, Y. pestis directly infects the release of endotoxins, leading to ischemic necrosis. After 36 h, the pro-inflammatory phase begins, where there is an upregulation of cytokine or chemokine levels, resulting in a critical point that can lead to death [40]
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