1.3 Yersinia Pestis

Yersinia genus contains how many species clusters

14

Are all yersinia cluster pathogenic

No there are pathogenic and nonpathogenic

Why is Yersinia genus used to study pathogenic evolution

It contains both pathogenic and nonpathogenic species, allowing researchers to study long and short term evolution

Example of Yersinia long term evolution

Y. enterocolitica evolved over millions of
years from a non-pathogenic ancestor

Example of Yersinia short term evolution

Y. pestis recently evolved only thousands of years
ago from Y. pseudotuberculosis

Y. enterocolitica and Y. pseudotuberculosis

zoonotic pathogens that cause self-limiting gastroenteritis following the ingestion of contaminated food

Which Yersinia species are enteropathogens and why

Y. enterocolitica and Y. pseudotuberculosis are enteropathogens because they cause gastroenteritis

Y. pestis

Zoonotic agent that causes the plague as it is transmitted from fleas/rodents to humans

The mammalian pathogens of the Yersinia genus are present in

two distinct lineages, the formation of
which were marked by key gene gain and gene loss events

Y. pestis evolved from which species

Y. pseudotuberculosis through gene acquisition and loss.

Prominent gene gain events (foothold moments) during evolution of pathogenic Yersinia

acquisition of the pYV virulence plasmid

pYV virulence plasmid

encodes the Ysc type III secretion system (T3SS)

Y, pestis morphology

Gram-negative coccobacillus

First pandemic caused by Y. pestis

Plague of Justinian, which killed 25-50% of Europe

Second Y. pestis pandemic

Balck death, which killed 25% of the world

Y. pestis is transmitted through

flea bites, direct contact, and respiratory droplets.

What type of threat is Y. pestis categorized as

Cat A (highest potential threat)

Plagues caused by Y. pestis

Bubonic
Pneumonic
Septicemic

Y. pestis- Bubonic plague

Infection following flea bite causing painful bubos (high mortality untreated)

Bubos

Painful a lethal swelling of lymph nodes

Y. pestis- Pneumonic plague

Infection following aerosol exposure leading to severe respiratory symptoms and high mortality if untreated.

Y. pestis septicemic plague

usually follows bubonic infection that spreads to the bloodstream, causing sepsis and potentially leading to multi-organ failure.

When did Y. pestis evolve from Y. pseudotuberculosis

5 to 10 thousand years ago (very recently and quick)

How is Y. pestis different from Y. pseudotuberculosis

It has no intestinal disease and is transmitted by flea vector

Why did Y. pestis lose ability to colonize intestines

~150 pseudogenes were identified in Y. pestis that are involved in intestinal colonization, suggesting a loss of function in this area.

Which elements are highly prevalent in Y. pestis genome and why

Insertion sequences due to frequent genome rearrangements

Y. pestis-specific plasmid pFra

Encodes ymt genes that allow Y. pestis to survive in the flea vector and enhance its virulence.

Y. pestis- ymt genes

Promotes flea borne transmission but not virulence by allowing biofilm formation in flea gut

How do we know that ymt promotes flea gut colonization but not virulence

ymt genes are essential for colonization of the flea gut, strains lacking these genes can still cause disease in mammalian hosts, indicating that ymt is not directly linked to virulence.

Yersinia hemin storage locus (hms)

A set of genes that enables Yersinia to store hemin in, which is crucial for biofilm formation and contributes to its transmission.

Hms regulation- positive control

c-di-GMP presence increases biofilm formation by increasing transcription of hms genes

Hms regulation- negative control

RcsAB DNA-binding repressor protein prevents transcription of hms genes

Why does Y. pestis have enhance biofilm formation

Mutated PDEs and RcsA repressor protein

What is the effect of the Y. pestis mutated PDE and rcsA

lead to increased c-di-GMP levels, enhancing biofilm formation by promoting the transcription of hms genes.

Why did Y. pestis lose the ability to transmit through aerosol like its ancestor Y. pseudotuberculosis

Urease is needed for oral transmission, but it is toxic to fleas, so urease activity was selected against

How did Y. pestis loss the urease enzyme needed for oral transmission

due to ureD mutation

Y. pestis pPla plasmid

harbors the virulence factor plasminogen activator (Pla)

Why does Y. pestis need Pla virulence factor

enabling bacteria to disseminate from the
local site of infection into the lymphatics to form buboes

During bubonic plaque, why do groin lymph nodes swell first

they are usually the closest to the flea bite site on the lower extremities, where the infection begins

Paleomicrobiology

microbiological study of prehistoric material and, in part due to well-kept burial records of plague victims, genomic studies of Y. pestis have been major
contributors to this field

Overtime ancient DNA is ____

fragments by oxidative and hydrolytic damage

Deamination

Cytosine is degraded to uracil

Obvious sign of DNA deamination

Presence of uracil in DNA

Why is deamination the most analyzed DNA degradation pattern

ensures reliable results since contaminating molecules are unlikely to show these signatures

DNA capture arrays

Used to enrich DNA isolated from the teeth of black death victim for analysis of Yersinia pestis.

DNA capture arrays were used to analyze victims from which 2 plagues

the Black Death and the Justinian Plague.

Why were later plague victims analyzed with a metagenomic shotgun sequencing approach instead of DNA arrays

to capture a broader and more unbiased representation of the genetic material, allowing for the detection of a wider variety of genes and sequence variations

Unique findings of metagenomic shotgun sequencing appraoch for Y. pestis vitctims

Not all bronze age Y. pestis had acquired Ymt toxin

Y. pestis biovars

Subdivisions based on sugar fermentation and nitrate reduction

Strains associated with the 1st (Justinian Pandemic)

Phylogenetically distinct from 2nd and 3rd plague, and appear to have no living descendants

The strains associated with the 2nd (Black death pandemic)

Phylogenetic position suggests that this strain gave rise to ALL LATER Y. PESTIS STRAINS

Strain associated with 3rd pandemic (China)

1.ORI group which started in china and spread globally.

How did the plague get to the US

1.ORI isolate spread from China, to Hong Kong, to the US on a ship in 1899

all Y. pestis isolates in the United States are

derived from the 3rd pandemic strain, 1.ORI from china

Relationship between second pandemic strain and third

During seconds pandemic Y. pestis spread from Asia to Europe, then it went back to China and re-emerged as the third pandemic strain, which was more virulent.