The PlagueThe Plague((Y. PestisY. Pestis))

Eti Mezei, Elodi Dielubanza, Clara BoydEti Mezei, Elodi Dielubanza, Clara Boyd

Overview - 3 Types of PlagueOverview - 3 Types of PlagueBubonicBubonic PneumonicPneumonic SepticemicSepticemic- Most common form- Most common form

- Responsible for most - Responsible for most plague epidemicsplague epidemics

- Generally secondary - Generally secondary complication of complication of bubonic plague bubonic plague though can be a though can be a primary infectionprimary infection

- Diagnosis is more - Diagnosis is more difficult difficult

- Easily communicable- Easily communicable

- Generally secondary - Generally secondary complication of complication of bubonic plague bubonic plague though can be a though can be a primary infectionprimary infection

- Poses the greatest - Poses the greatest burden to the human burden to the human system of the 3 typessystem of the 3 types

All types of plague are caused by the gram-negative bacteria All types of plague are caused by the gram-negative bacteria Yersinia PestisYersinia Pestis

Epidemiology Epidemiology Historical & Modern AspectsHistorical & Modern Aspects

Reservoirs, VectorsReservoirs, VectorsTransmissionTransmissionWorld HistoryWorld HistoryDiscoveriesDiscoveriesModern PlagueModern PlagueTrends in the USATrends in the USA

Reservoirs Vectors Incidental HostsUrban and domestic rats Ground squirrels Rock squirrels Prairie dogs Deer mice Field mice Gerbils Voles Chipmunks Marmots Guinea pigs Kangaroo Rats

Xenopsylla cheopis (the oriental rat flea; nearly worldwide in moderate climates) Oropsylla montanus (United States)

Nosopsyllus fasciatus (nearly worldwide in temperate climates) Xenopsylla brasiliensis (Africa, India, South America)

Xenopsylla astia (Indonesia and Southeast Asia)

Xenopsylla vexabilis (Pacific Islands)

HumansDomestic and feral cats Dogs Lagomorphs (rabbits and hares) Coyotes Camels Goats Deer Antelope

Reservoirs & VectorsReservoirs & Vectors

Modes of TransmissionModes of Transmission

■ ■ FleabiteFleabite

■■ Inhalation of salivary droplets of infected humans or Inhalation of salivary droplets of infected humans or catscats

■■ Cat’s scratchCat’s scratch

■■ Ingestion of the bacillus Ingestion of the bacillus

■■ Contact with infected body fluidsContact with infected body fluids

Bubonic Septicemic Pneumonic

1 Y. Pestis enters the lymphatic system through the skin

Bite from infected flea

Direct inoculation of Y. Pestis into bloodstream

Bite from infected flea; Scratch from infected cat; Contact with Infected Fluids

Direct inhalation or ingestion of Y.Pestis

Inhaling droplets from cough of infected human/cat; Eating infected animal; Inhaling Y. Pestis in the lab

2-----------------

As a complication of bubonic or 1 pneumonic plague

Via hematogenous spread, as a complication of bubonic or septicemic plague

Transmission & Type of PlagueTransmission & Type of Plague

Transmission CyclesTransmission Cycles

Plague and World HistoryPlague and World History 1320 B.C1320 B.C.. -- 1 -- 1stst mention of plague is in the Bible mention of plague is in the Bible

Philistines stole the ark of the covenant from the Philistines stole the ark of the covenant from the Israelites and plague ensued:Israelites and plague ensued:

[t]he Lord’s hand was heavy upon the people of Ashdod and its vicinity. He [t]he Lord’s hand was heavy upon the people of Ashdod and its vicinity. He brought devastation upon them and afflicted them with tumors. And rats brought devastation upon them and afflicted them with tumors. And rats appeared in their land, and death and destruction were throughout the city…appeared in their land, and death and destruction were throughout the city…[T]he Lord’s hand was upon that city, throwing it into great panic. He [T]he Lord’s hand was upon that city, throwing it into great panic. He afflicted both young and old with and out break of tumors in the groin.afflicted both young and old with and out break of tumors in the groin.

Plague and World HistoryPlague and World History541-700 A.D. – 1541-700 A.D. – 1stst Pandemic, Justinian Plague Pandemic, Justinian Plague

■■ Began in Pelusium Egypt and Began in Pelusium Egypt and spread to the middle Eastspread to the middle East & Europe with estimated population & Europe with estimated population losses of 50-60% in N. Africa, losses of 50-60% in N. Africa, Europe & S. Asia. Europe & S. Asia.

■■ A.D. 558-654: The 2A.D. 558-654: The 2ndnd through 11 through 11thth epidemics occurred epidemics occurred in 8-12 year cycles.in 8-12 year cycles.

Plague and World HistoryPlague and World History1346-1666 – 21346-1666 – 2ndnd Pandemic, Pandemic, Black DeathBlack Death Plague believed to have entered Europe along tradePlague believed to have entered Europe along trade routes from central Asia by fleas in bundles of imported fur.routes from central Asia by fleas in bundles of imported fur.

1347-1351: 11347-1351: 1stst 5-year epidemic killed an estimated 17-28 million 5-year epidemic killed an estimated 17-28 million people, 30-40% of Europe’s population at the time. people, 30-40% of Europe’s population at the time.

Epidemics continued throughout the period in 2-5 year cycles until Epidemics continued throughout the period in 2-5 year cycles until 1480 and then with less frequency until late 171480 and then with less frequency until late 17thth century. century.

The plague stimulated significantThe plague stimulated significant advance in medical practice includingadvance in medical practice including the beginnings of clinical research,the beginnings of clinical research, reorganization of hospitals.reorganization of hospitals.

A Plague DoctorA Plague Doctor

NOTE:NOTE: other epidemics existing at the time of the 1st and 2nd Plague pandemics may other epidemics existing at the time of the 1st and 2nd Plague pandemics may have contributed to depopulation figureshave contributed to depopulation figures

Plague and World HistoryPlague and World History1855 – 31855 – 3rdrd Pandemic, China Pandemic, China ■■ Began in the Yünnan province and troops from the war in that area helped to Began in the Yünnan province and troops from the war in that area helped to

spread plague down the southern coast to Hong Kong and Canton by 1894 spread plague down the southern coast to Hong Kong and Canton by 1894 and Bombay by1898.and Bombay by1898.

By 1900 steamships had helped to spread the disease to Africa, Austrailia, By 1900 steamships had helped to spread the disease to Africa, Austrailia, Europe Hawaii, India, Japan, the Middle East, the Phillipines, the U.S, and S. Europe Hawaii, India, Japan, the Middle East, the Phillipines, the U.S, and S. America. By 1903, 1 million people/year were dying of plague in India. America. By 1903, 1 million people/year were dying of plague in India.

Mukden, China, 1910-11: Workers in a plague hospital hose off an autopsy table with carbolic spray

Plague and World HistoryPlague and World History1855 – 31855 – 3rdrd Pandemic, China (cont’d) Pandemic, China (cont’d)

Stable enzootic foci were established on every inhabited continent Stable enzootic foci were established on every inhabited continent except Austrailia and outbreaks continue until today though greatly except Austrailia and outbreaks continue until today though greatly reduced because of advances in public health practices and drugs.reduced because of advances in public health practices and drugs.

Significantly, it is during the 3Significantly, it is during the 3rdrd Pandemic that the bacterium Pandemic that the bacterium responsible for plague as well as its vectors and reservoirs were responsible for plague as well as its vectors and reservoirs were identified.identified.

History of History of Yersina PestisYersina Pestis First discovered in 1894 during the Hong Kong Plague by two First discovered in 1894 during the Hong Kong Plague by two

independent investigators (Alexandre Yersin and Shibasaburo Kitasato) independent investigators (Alexandre Yersin and Shibasaburo Kitasato) within days of each other.within days of each other.

Kitasato was initially credited for the discovery but Yersin’s bacillus Kitasato was initially credited for the discovery but Yersin’s bacillus proved to be the infecting bacillus.proved to be the infecting bacillus.

Yersin drained buboes of deceased plague victims and identified the Yersin drained buboes of deceased plague victims and identified the bacillus with microscopy.bacillus with microscopy.

Confirmed the involvement of the bacillus in infection by injecting healthy Confirmed the involvement of the bacillus in infection by injecting healthy rodents with infected lymph isolates. Healthy animals developed plague rodents with infected lymph isolates. Healthy animals developed plague symptoms and dissection showed blood and organs to be filled with the symptoms and dissection showed blood and organs to be filled with the isolated bacillus.isolated bacillus.

YY Nomenclature: the plague bacillus has had four name Nomenclature: the plague bacillus has had four name

changes. changes.

Classifications:Classifications:Bacterium PestisBacterium Pestis until 1900 until 1900Bacillus PestisBacillus Pestis until 1923 until 1923Pasturella PestisPasturella Pestis (after Yersin’s mentor) (after Yersin’s mentor) Yersinia PestisYersinia Pestis in 1970 until present day in 1970 until present day

Identification of Vectors and Identification of Vectors and ReservoirsReservoirs

■■ Yersin also confirmed the Black rat (Yersin also confirmed the Black rat (Rattus rattusRattus rattus) as the ) as the reservoir after local suspicion implicated its involvement in reservoir after local suspicion implicated its involvement in the transmission of the plague.the transmission of the plague.

■■ In 1897 during the Indian outbreak, Paul- Louis Simond In 1897 during the Indian outbreak, Paul- Louis Simond and Masanori Ogata identified the oriental rat flea and Masanori Ogata identified the oriental rat flea ((XenopsyllaXenopsylla CheopisCheopis) as the transmission vector by ) as the transmission vector by exposing healthy rodents to fleas collected from the exposing healthy rodents to fleas collected from the corpses of rats which had died recently from plague.corpses of rats which had died recently from plague.

Early Prevention and Early Prevention and Treatment MethodsTreatment Methods

YersinYersin isolated serum from horses immunized with the isolated serum from horses immunized with the bacillus for treatment of human plague in 1896.bacillus for treatment of human plague in 1896.

W.M HaffkineW.M Haffkine created and used an effective preventative created and used an effective preventative vaccine for the Plague containing killed bacteria during the vaccine for the Plague containing killed bacteria during the Manchurian outbreak (1910).Manchurian outbreak (1910).

L.T WuL.T Wu characterized pneumonic plague during the 1910 characterized pneumonic plague during the 1910 Manchurian outbreak and helped to institute protective Manchurian outbreak and helped to institute protective measures against aerosol spread of the disease.measures against aerosol spread of the disease.

Modern PlagueModern Plague For most of the 20For most of the 20thth century the occurrence of plague century the occurrence of plague

has sharply decreased though not disappeared. Plague has sharply decreased though not disappeared. Plague remains an enzootic infection of rats, ground squirrels remains an enzootic infection of rats, ground squirrels and other rodents in every inhabited continent except and other rodents in every inhabited continent except Austrailia.Austrailia.

Why has Plague decreased so sharply?Why has Plague decreased so sharply? The WHO credits public health prevention protocols and The WHO credits public health prevention protocols and

the development of effective antibiotics.the development of effective antibiotics.

Modern PlagueModern Plague WHO reports 1000-3000 cases of plague worldwide annually WHO reports 1000-3000 cases of plague worldwide annually (avg.1700cases/year for the last 50 years) (conservative estimate)(avg.1700cases/year for the last 50 years) (conservative estimate)

Plague is largely underreported in countries with limited surveillance Plague is largely underreported in countries with limited surveillance and laboratory capabilities.and laboratory capabilities.

Modern plague is primarily occurrent in rural areas with poor Modern plague is primarily occurrent in rural areas with poor sanitation and large rodent populations.sanitation and large rodent populations.

Urban cases are increasingly rare. Los Angeles1924 was the last Urban cases are increasingly rare. Los Angeles1924 was the last U.S urban outbreak.U.S urban outbreak.

Modern Plague - DistributionModern Plague - Distribution

* largest enzootic foci are in the Southwestern &Pacific U.S and the * largest enzootic foci are in the Southwestern &Pacific U.S and the former USSR.former USSR.

Modern Plague – Modern Plague – # Cases Reported to WHO 1954-1997# Cases Reported to WHO 1954-1997

Modern Plague - TimelineModern Plague - Timeline 19001900 - Plague officially arrives in the - Plague officially arrives in the U.SU.S. Infected corpse of . Infected corpse of

Chinese Laborer found in San Francisco hotel basement.Chinese Laborer found in San Francisco hotel basement.

1924 1924 - - Los AngelesLos Angeles. 33 cases, 31 fatal. 1. 33 cases, 31 fatal. 1stst case, Mexican case, Mexican American male, misdiagnosed with STD, family and neighbors American male, misdiagnosed with STD, family and neighbors contract plague and die with in two weeks. Many die before contract plague and die with in two weeks. Many die before public health measures were taken.public health measures were taken.

1967-72 1967-72 - - VietnamVietnam. Defoliation, disturbance of the ecosystem and . Defoliation, disturbance of the ecosystem and economic losses during the war contributed to outbreak. Singular economic losses during the war contributed to outbreak. Singular contributor to the 1967 jump in worldwide plague vases.contributor to the 1967 jump in worldwide plague vases.

1992 1992 - - ArizonaArizona. 1 confirmed case, 1 fatality. Misdiagnosis of . 1 confirmed case, 1 fatality. Misdiagnosis of pneumonia. Post-mortem lab tests confirmed pneumonia. Post-mortem lab tests confirmed Y. PestisY. Pestis. Family . Family cat identified as source.cat identified as source.

■ ■ 19941994 – – IndiaIndia. .

Bubonic plague begins when rats arrive Bubonic plague begins when rats arrive because of stockpiles of relief grain. because of stockpiles of relief grain. Pneumonic form shortly follows.Pneumonic form shortly follows.

5150 suspected pneumonic and bubonic 5150 suspected pneumonic and bubonic cases from 26 states. 163 confirmed with cases from 26 states. 163 confirmed with serology, 53 confirmed deaths, 300 serology, 53 confirmed deaths, 300 suspected. suspected.

Mass panic; 600,00 flee Surat including 110 Mass panic; 600,00 flee Surat including 110 plague cases.plague cases.

Timeline Cont’dTimeline Cont’d

■■ 19971997ZambiaZambia- Jan. Namwala region 90 cases of bubonic plague, 22 fatal. - Jan. Namwala region 90 cases of bubonic plague, 22 fatal. Heavy rains drove rats into inhabited regions.Heavy rains drove rats into inhabited regions.

MozambiqueMozambique - Aug. Tete province. 115 reported cases of bubonic.- Aug. Tete province. 115 reported cases of bubonic.No reported deaths.No reported deaths.

MalawiMalawi - Oct. Southern region, 43 reported cases, 17 of which were seropostive. >60% cases - Oct. Southern region, 43 reported cases, 17 of which were seropostive. >60% cases were children. No reported deaths.were children. No reported deaths.

MozambiqueMozambique - Nov. August outbreak continues and extends to 225 cases. - Nov. August outbreak continues and extends to 225 cases. No reported deaths.No reported deaths.

■■ 19991999NamibiaNamibia - May Northwest region, 39 reported cases, 8 deaths. - May Northwest region, 39 reported cases, 8 deaths.

MalawiMalawi - July Reported cases in 22 villages, 74 suspected cases total. - July Reported cases in 22 villages, 74 suspected cases total.No reported deaths.No reported deaths.

Timeline Cont’dTimeline Cont’d

■■ 20012001ZambiaZambia - Mar. Nyanje and Petauke regions 436 suspected cases, - Mar. Nyanje and Petauke regions 436 suspected cases, 11 deaths. 11 deaths. Y. PestisY. Pestis postively identified. postively identified.

■■ 20022002IndiaIndia - Feb. Hat Koti village. 16 cases of pneumonic plague - Feb. Hat Koti village. 16 cases of pneumonic plague including 4 deaths. Cases linked to one villager.including 4 deaths. Cases linked to one villager.

Malawi- June. Nsanje region and 26 nearby villages. 71 reported Malawi- June. Nsanje region and 26 nearby villages. 71 reported cases of bubonic plague. cases of bubonic plague.

■■ 20032003New YorkNew York - Nov. 2 cases. Couple contracts plague in Santa Fe, - Nov. 2 cases. Couple contracts plague in Santa Fe, NM and travels to New York. Neither case fatal but man required NM and travels to New York. Neither case fatal but man required double foot amputation.double foot amputation.

Timeline Cont’dTimeline Cont’d

Plague Patient Returns HomeNEW YORK, Feb. 10, 2003

A New Mexico man who was hospitalized in New York City for more than three months with bubonic plague left the hospital to fly home on Monday, a spokesman said.

John Tull left Beth Israel Medical Center at about 7 a.m., hospital spokesman Mike Quane said. Tull was admitted to Beth Israel on Nov. 5.

Tull, whose feet were amputated due to extensive tissue damage, will begin physical therapy in Albuquerque, N.M., Quane said.

Disease investigators believe Tull and his wife, Lucinda Marker, contracted plague from infected fleas on their Santa Fe, N.M., ranch. They became ill after arriving in New York on Nov. 1 for vacation.

John Tull at the Beth Israel Hospital in New York City with his wife Lucinda Marker.

CBSNEWS.com

Trends in Human Plague Trends in Human Plague in the U.S.in the U.S.

From 1899-1926 Plague in the U.S. was an urban From 1899-1926 Plague in the U.S. was an urban epidemic involving domesticated rats with cases most epidemic involving domesticated rats with cases most prevalent in California and Hawaii.prevalent in California and Hawaii.

Late 1940’s saw a jump in infection in the Southwestern Late 1940’s saw a jump in infection in the Southwestern states which remain hotspots for infection.states which remain hotspots for infection.

Static annual infection levels from 1925-1964 (avg.<2 Static annual infection levels from 1925-1964 (avg.<2 cases/year). 1965 saw increases that would carry into cases/year). 1965 saw increases that would carry into the 80’s.the 80’s.

Trends in Human Plague Trends in Human Plague in the U.Sin the U.S

Seasonal distribution: 1926-1979 81.5% of plague cases Seasonal distribution: 1926-1979 81.5% of plague cases occurred in May-September. Prior to 1926 most were occurred in May-September. Prior to 1926 most were Sept.-Oct.Sept.-Oct.

1970-1980 1970-1980 53% cases 53% cases ♀ ♀ 59% were < 20 years old. 59% were < 20 years old. Similar age distribution from 1926-1969Similar age distribution from 1926-1969

Racial dist.: 1970-79 35% of cases were in Indians (1.4 Racial dist.: 1970-79 35% of cases were in Indians (1.4 Indians per 100,00 compared to 0.1non-Indians).Indians per 100,00 compared to 0.1non-Indians).

Simplified PathogenesisSimplified Pathogenesis(Focus on Bubonic Plague)(Focus on Bubonic Plague)

Flea feeds on Y. Pestis-infected blood

Y. Pestis enters flea’s midgut & multiplies logarithmically

Clump of Y.Pestis & fibronous material forms in the midgut,

blocking flea’s proventriculus

During next meal, blood cannot enter the midgut & flea gets very hungry

Flea bites vigorously & regurgitates the contents of its midgut into the next wound

PathogenesisPathogenesis

“Blocked” Flea

ENTRY:Flea bite -- regurgitation of bloodcontaining Y. Pestis(≈ 25,000 -100,000 organisms) intointerstitial space of subcutaneoustissue

DISSEMINATION:Superficial lymph vessels drain skin & subcutaneous tissue --Y. Pestis enters the lymphatic system

PathogenesisPathogenesis

DISSEMINATION: Y. Pestis migrates through lymphvessels to regional lymph node

PathogenesisPathogenesis

Massive inflammatory response obliterates underlying lymph node architecture -- leads to painful swellings (Buboes)

HEMATOGENOUS DISSEMINATION:Y. Pestis may enter the blood stream at the lymph node, and can then travelto other organs (liver, spleen).(= 2 Septicemic Plague)

HEMATOGENOUS DISSEMINATION:Once in the bloodstream, Y. Pestis also has the opportunityto enter the lungs. (2 Pneumonic Plague)

PathogenesisPathogenesis

Molecular Biology Molecular Biology of of Yersinia PestisYersinia Pestis

Bacteriological CharacteristicsBacteriological CharacteristicsEvolutionEvolutionBiovarsBiovarsGenomeGenomeMolecular PathogenesisMolecular Pathogenesis Proteins/Virulence Factors/Proteins/Virulence Factors/ ImmunologyImmunology

Bacteriological CharacteristicsBacteriological Characteristics Gram negativeGram negative

Non-motileNon-motile

Enterobacteriacae Enterobacteriacae

Non-spore forming Non-spore forming coccobacilluscoccobacillus

Facultative anaerobeFacultative anaerobe

Obligate parasiteObligate parasite

Bacteriological CharacteristicsBacteriological Characteristics .5-.8 uM in diameter.5-.8 uM in diameter

1-3 uM long1-3 uM long

Grows optimally at 28° C Grows optimally at 28° C and a pH of 7.2-7.6and a pH of 7.2-7.6

Bacterial cell wallBacterial cell wall

Protein Envelope (F1)Protein Envelope (F1)

Evolution of Evolution of Y. PestisY. Pestis There are 11 species of Yersinia There are 11 species of Yersinia 3 pathogenic species of Yersinia3 pathogenic species of Yersinia

Yersinia PseudotuberculosisYersinia Pseudotuberculosis - enteropathogen - enteropathogen Yersinia EnterocolitisYersinia Enterocolitis - enteropathogen - enteropathogen Yersinia PestisYersinia Pestis - systemic pathogen - systemic pathogen

Y. PestisY. Pestis evolved from evolved from Y.pseudotuberculosisY.pseudotuberculosis 1500-4000 years ago1500-4000 years ago

90% chromosomal DNA relatedness90% chromosomal DNA relatedness Physiological and antigenic similaritiesPhysiological and antigenic similarities

Y. PseudotuberculosisY. Pseudotuberculosis Y. PestisY. Pestis DiseaseDisease

Bubonic PlagueBubonic Plague

TransmissionTransmission Flea, mammal, never Flea, mammal, never

found in free environmentfound in free environment

PseudogenesPseudogenes YadA, Inv, O antigenYadA, Inv, O antigen

Extrachromosomal DNAExtrachromosomal DNA pCD1pCD1 pFrapFra pPstpPst

Pathogenicity IslandsPathogenicity Islands

DiseaseDisease Enteric infection Enteric infection

TransmissionTransmission Enters mammals through Enters mammals through

food and waterfood and water

GenesGenes YadA, Inv, O antigenYadA, Inv, O antigen

Extrachromosomal DNAExtrachromosomal DNA pCD1pCD1

Biovars of Biovars of Y.PestisY.Pestis 3 biovars named based 3 biovars named based

on their ability to convert on their ability to convert nitrate to nitrite and nitrate to nitrite and ferment glycerolferment glycerol

AntiquaAntiqua (1 (1stst pandemic) pandemic) MedievalisMedievalis (2 (2ndnd pandemic) pandemic) OrientalisOrientalis (3 (3rdrd pandemic) pandemic)

GlycerolGlycerol NitriteNitrite + ++ + + -+ - - +- +

GenomeGenome 4500 genes4500 genes

One chromosome- 4.6MbOne chromosome- 4.6Mb Pathogenicity islands (pgm locus)Pathogenicity islands (pgm locus)

Three plasmidsThree plasmids pFra – 96.2 kbpFra – 96.2 kb pPst1- 9.7 kbpPst1- 9.7 kb pCD1- 70.3kbpCD1- 70.3kb

Chromosome Pgm locusChromosome Pgm locus 102 kb pathogenicity island in the chromosome102 kb pathogenicity island in the chromosome

contains three hemin storage genes (contains three hemin storage genes (HmsHms)) These genes only found in These genes only found in Y.pestisY.pestis They are essential for flea blockageThey are essential for flea blockage Allow Allow Y. PestisY. Pestis to store large quantities of hemin (iron source) in its outer to store large quantities of hemin (iron source) in its outer

membranemembrane

Bacteria requires iron in order to cause infectionBacteria requires iron in order to cause infection

An inorganic iron transport system (An inorganic iron transport system (ybtybt) (a sidephore) is ) (a sidephore) is encoded within Pgm locusencoded within Pgm locus

Ybt chelates iron bound to eukaryotic proteins and Ybt chelates iron bound to eukaryotic proteins and transports them to the bacteriumtransports them to the bacterium

pFrapFra 60-280 kb (depending on the strain)60-280 kb (depending on the strain)

Found only in Found only in Y. PestisY. Pestis

Contains gene for murine toxin (Contains gene for murine toxin (YmtYmt) ) Two forms of a protein toxic for mice and ratsTwo forms of a protein toxic for mice and rats

Proposed as B-adrenergic antagonistProposed as B-adrenergic antagonist

Ymt transcription is threefold higher at 26°C(flea) than at Ymt transcription is threefold higher at 26°C(flea) than at 37°C(mammal). 37°C(mammal).

This gene is believed to be essential for flea colonizationThis gene is believed to be essential for flea colonization

pFrapFra Contains structural and regulatory genes that Contains structural and regulatory genes that

encodes F1 protein capsule (encodes F1 protein capsule (caf1caf1))

F1 is a proteinacious capsule that forms at 37°C F1 is a proteinacious capsule that forms at 37°C (mammal) but not 26°C (flea)(mammal) but not 26°C (flea)

F1 capsule makes bacterium resistant to F1 capsule makes bacterium resistant to phagocytosis by monocytes phagocytosis by monocytes

Resistance to phagocytosis by monocytes allows Resistance to phagocytosis by monocytes allows journey from dermis to viscerajourney from dermis to viscera