Lecture 08_Hai_2025

Lecture 8: Yersinia Pestis and Plague

Overview of Yersinia Pestis

  • Type: Gram-negative coccobacillus.

  • Etiology: Known for causing plague, famously recognized for leading to the Black Death.

  • Evolution: Evolved from Yersinia pseudotuberculosis in the last 1500-2000 years.

  • Hosts: Affects humans, rodents, and arthropods (fleas).

Historical Discovery

  • Identified by: Alexandre Yersin and Kitasato Shibasaburo (1894).

  • Context: Emerged from an outbreak of pneumonic plague in China.

Forms of Plague in Humans

  • Bubonic Plague:

    • Symptoms: Hemorrhaging, inflamed lymph nodes (buboes).

    • Transmission: Bites from infected fleas.

  • Septicemic Plague:

    • Symptoms: Disseminated infection leading to skin hemorrhages.

    • Mortality: ~100% untreated.

  • Pneumonic Plague:

    • Symptoms: Lung infection, highly infectious.

    • Transmission: Primarily through aerosols; can spread from other infected tissues.

Severity of Plague

  • Bubonic Plague: Untreated fatality rate of 50-60%.

  • Septicemic Plague: Nearly 100% fatal without treatment.

  • Pneumonic Plague: Almost 100% fatal if untreated; very contagious.

Historical Pandemics

  • 1st Pandemic (542 AD): >25 million deaths in initial outbreak.

  • 2nd Pandemic (14th Century): Known as the Black Death; 200 million deaths across Europe.

  • 3rd Pandemic (ended 1990s): 20 million deaths in India alone.

Plague Today

  • Last US Epidemic: 1924-25 in Los Angeles.

  • Current Status: Regarded as a re-emerging infectious disease.

  • Public Health: Modern medicine mitigates risks but requires vigilance.

  • Bioterrorism Concerns: Historical attempts to weaponize plague during sieges.

Treatment Options

  • Antibiotics: Must be administered promptly due to rapid disease progression.

  • Vaccine: Currently unavailable in the US.

  • Drug Resistance: Emergence of multiple-drug resistant strains (e.g., in Madagascar).

Animal Vectors and Transmission Cycles

  • Zoonotic Pathogen: Spread from rodents to humans via infected fleas.

  • Reservoirs:

    • Sylvatic Cycle: Includes wild rodents and their fleas.

    • Urban Cycle: Domestic black rat and oriental rat flea.

  • Transmission Pathways: Direct contact, flea bites, and secondary spread via pneumonic plague.

Flea Vector Dynamics

  • Primary Vector: Xenopsylla cheopis (oriental rat flea).

  • Mechanism: Y. pestis forms biofilms in flea gut, causing starvation and leading to regurgitation of bacteria during feeding.

Virulence Factors

  • Plasmids: Multiple virulence plasmids (pPCP1, pPMT1/pFra, pCD1) involved in pathogenicity.

  • Type III Secretion System (T3SS): Mediates host immune evasion and bacterial adhesion.

  • Key Effectors: Yop proteins disrupt host cell functions and can induce apoptosis in immune cells.