Disease relevance of Plague

• Yersinia, the causative bacteria of the bubonic plague and other enteric diseases, secrete an active PTPase, Yop51, that enters and suppresses host immune cells [1].

High impact information on Plague

• A Y. pestis strain lacking the plasmid-encoded cell-surface plasminogen activator, which is avirulent by intradermal or s.c. injection, was able to cause fatal primary septicemic plague at low incidence, but not bubonic plague, when transmitted by fleas [2].
• The prevailing hypothesis is that the selective rise of CCR5-Delta 32 to its current frequency can be attributed to bubonic plague [3].
• In Caenorhabditis elegans, mutations in the srf-3 locus confer resistance to infection by Microbacterium nematophilum, and they also prevent biofilm formation by Yersinia pseudotuberculosis, a close relative of the bubonic plague agent Yersinia pestis [4].
• In addition, a ybtP mutant showed reduced iron accumulation and was avirulent in mice by a subcutaneous route of infection that mimics flea transmission of bubonic plague [5].
• YopM, a member of the leucine-rich repeat protein superfamily, is an effector produced by the bubonic plague bacterium, Yersinia pestis, that is essential for virulence [6].

Chemical compound and disease context of Plague

• A mouse model was developed to evaluate the efficacy of antibiotic treatment of pneumonic plague; streptomycin was compared to antibiotics with which there is little or no clinical experience [7].
• These studies indicate that netilmicin, gentamicin, ciprofloxacin, and ofloxacin may be alternatives for the treatment of pneumonic plague in humans [7].
• Yersinia pestis, which causes bubonic and pneumonic plague, forms pigmented red colonies on Congo red (CR) dye agar [8].
• A single, subcutaneous, 30-microg dose of either a combination of the Yersinia pestis proteins F1+V or a F1-V fusion protein adsorbed to the adjuvant aluminum hydroxide, protected Hsd:ND4 mice for one year against pneumonic plague [9].
• The efficacies of prophylactic and therapeutic gatifloxacin and moxifloxacin were assessed in a BALB/c mouse model of systemic and pneumonic plague and compared with ciprofloxacin [10].

Anatomical context of Plague

• The response regulator PhoP was previously shown to be important for Y. pestis survival in macrophages and for virulence in a murine bubonic plague infection assay [11].

Gene context of Plague

• A recent and prevalent mutation in the chemokine receptor CCR5 in humans of northern European ancestry has been proposed to provide protection against bubonic plague [12].
• Previously it was shown that a deletion of the Hmu system had no effect on the virulence of Y. pestis in a mouse model of bubonic plague [13].
• Intratracheal delivery of aerosolized monoclonal antibodies with specificity for Yersinia pestis LcrV and F1 antigens protected mice in a model of pneumonic plague [14].
• The current human whole-cell vaccine is ineffective against pneumonic plague caused by typical F1 capsule positive (F1+) strains of Yersinia pestis [15].
• We conclude that in this animal model of pneumonic plague, intra-nasal administration of microgram quantities of Yersinia pestis subunits confers protective immunity, provided the vaccines are microencapsulated or admixed with a strong mucosal adjuvant, such as the cholera toxin B subunit [16].

Analytical, diagnostic and therapeutic context of Plague

• Persons who come in contact with patients with pneumonic plague should receive antibiotic prophylaxis with doxycycline or ciprofloxacin for 7 days [17].

References