Lecture 5: Yersinia and Bordetella

2 primary classes of Gram-negative coccobacilli

Yersinia

Bordetella

Genus Yersinia: part of what family

Enterobacteriaceae family

Genus Yersinia: shape and stain pattern

coccobacilli/bacilli (bipolar ‘safety pin’ staining)

Genus Yersinia: motility, temperature class, oxygen class, intra or inter

Non-motile, psychrophilic, facultative intracellular anaerobes

Genus Yersinia: how many species are pathogenic to humans

3: Y. enterocolitica, Y. pseudotuberculosis, Y. pestis

Genus Yersinia: Y. enterocolitica & Y. pseudotuberculosis

diarrheal GI disease “yersiniosis”

Genus Yersinia: Y. pestis

Evolved from Y. pseudotuberculosis

Causative agent of plague “Black death”

Yersinia pestis: virulence

Highly virulent pathogen

Yersinia pestis: where does it live

Lives in small rodents throughout the world

Yersinia pestis: what does it cause

Causes plague - a life threatening bacterial infection

Black Death/pestilence

Black death is historically responsible for

widespread pandemics with high mortality (>250 million deaths)

Black death: cases per year

Currently 1K-5K cases reported worldwide per year (~7 annually in U.S.)

Y. pestis: type of infection

zoonotic

Y. pestis: natrual reservoir

Rodents

Multiplies in blood stream, typically subclinical infection

Y. pestis: biologic vector

Fleas

Oriental rat flea (Xenopsylla cheopis) most efficient vector, but infects ~80 flea species

Y. pestis: transferred to mammal hosts by

flea bite

Y. pestis: steps of flea-mammal transmission

Multiplies in the flea's midgut after ingestion of a blood meal

Y. pestis biofilms block the flea's intestine; no more blood meal satiety, flea hungry

Flea then regurgitates the bacteria into the bite wound with each successive feeding attempt

Y. pestis: what can mammalian species serve as

“amplifying” hosts (severe, acute infection)

Y. pestis: what kinds of hosts are humans

incidental

Y. pestis: 4 ways it can be transmitted to humans

Bite of infected fleas (primary route); esp. in areas with low sanitation and rat infestations

Direct contact → Handling living or dead infected mammals

Inhalation of infectious respiratory droplets

Ingestion of infected rodent meat (e.g. by predators - cat); rare

Y. pestis: 3 forms of human disease

Bubonic plague

Septicemic plague

Pneumonic plague

*Depend on route of infection

Y pestis: initial disease symptoms

Initially flu-like symptoms develop after an incubation period of 3-7 days

Symptoms include sudden onset of fever, chills, head and body-aches, weakness, vomiting, nausea

Y. pestis: Bubonic plague

Y. pestis inoculated into body at site of flea bite

Travels through the lymphatic system to the nearest lymph node where it replicates

Infected lymph node becomes painfully inflamed and swollen (bubo)

Y. pestis: septicemic plague

Advanced stages of bubonic plague result in spread of Y. pestis in the blood

Can follow flea bite or direct contact with infective materials through cracks in the skin (no bubo)

rapidly progressive endotoxic shock, hemorrhagic necrosis (black death)

Y. pestis: pneumonic plague

Usually caused by spread to the lungs from advanced bubonic plague (septicemic)

Untreated pneumonic plague has a very high-fatality rate (~100%)

ONLY form spread person to person through infectious respiratory droplets

progression of plague types

bubonic can progress to septicemic which can progress to pneumonic

pneumonic can cause other cases of pneumonic

what does death occur from in septicemic plague

Death occurs from Gram-negative septic shock

what form of plague can cause plague epidemics

pneumonic plague

why is Y. pestis pathogenesis complex

due to insect and mammalian environments

optimal growth temperature range for Y. pestis

20-28C

complexity of virulence factors in Y. pestis

Some expressed primarily in flea; others only in mammals

Y. pestis: regulation of virulence factors

Regulatory systems respond to environmental triggers to turn production of necessary virulence factors on or off

Y. pestis: virulence factors induced at shift to 37C:

F1 protein capsule: antiphagocytic

Adhesins - Allow attachment to human cells

Type III secretion systems - Injection of proteins into host cells; cause cellular death

Yops (Yersinia outer proteins): cytotoxic & down-regulate anti-bacterial immune responses

Y. pestis: Diagnosis

Laboratory and molecular testing of clinical specimens (fluid from bubos, lungs, or blood)

Y. pestis: treatment

Rapid diagnosis and initiation treatment with an efficacious antibiotic within 24 hours of symptom onset is critical → plague is a potentially fatal disease

Y. pestis: untreated fatality rates

Untreated → fatal in ~50% of bubonic plague patients and in nearly 100% of patients suffering from septic or pneumonic plague

Y. pestis: treated fatality rates

With appropriate antimicrobial treatment → bubonic plague mortality is <10%, but remains high for pneumonic plague (~50%)

Y. pestis - Prevention

Improved sanitation, hygiene, and modern disease control methods have diminished cases

Prophylactic antibiotics prevent infection if you're at risk/been exposed to plague

If you live in / travel to regions where plague is endemic or an outbreak is occurring:

-Rodent-proof living areas: Remove potential rodent nesting areas (i.e. brush, rock, firewood and junk piles) and eliminate access to food sources (including pet food)

-Keep pets free of fleas

-Use insect repellent and protective clothing outdoors: Closely supervise children and pets when spending time outside in areas with large rodent populations

why can’t we eliminate the reservoir of Y. pestis

Entrenched in rodent populations globally

Y. pestis in bioterrorism

Y. pestis is classified as a Category A (tier 1) biologic agent for potential bioterrorism

Bordetella pertussis: growth, oxygen class, motility, capsule, nutrition, shape

Slow-growing, aerobic, motile, encapsulated, fastidious coccobacillus

Bordetella pertussis: kind of pathogen

Strict obligate human respiratory pathogen

Bordetella pertussis: causes what

Causes pertussis → highly contagious respiratory disease (aka whooping cough)

Hallmark of pertussis

Hallmark of disease → severe, spasmodic coughing episodes

Causes severe disease in children; esp. high mortality in infants

Bordetella pertussis: contagious + epidemiology

Highly contagious, infecting more than 90% of exposed susceptible persons

Today >90% of the cases are in developing nations; most deaths are among infants

Bordetella pertussis: vaccine introduction

Introduction of immunization in the 1940s produced a dramatic reduction in disease

Outbreaks persist in developed nations due to waning immunity

Bordetella pertussis - Transmission

Human to human only

Inhalation of infected airborne droplets primary mechanism of transmission

Also via direct contact with oral or nasal secretions of an infected individual

Bordetella pertussis - how long is the patient infectious

Patient infectious for ~3 weeks after the symptoms begin if untreated

VS

~ 5 days with treatment

Bordetella pertussis: where does bacteria bind

Bacteria bind ciliated respiratory epithelium of the upper airway (throat) and lungs

Bordetella pertussis: how is attachment mediated

Mediated by adhesins including: pili, filamentous hemagglutinin (FHA), and pertactin

Bordetella pertussis: exotoxins

Damage cells, impair cilia, trigger inflammation, increase mucus, immune evasion

Pertussis toxin (PT), Tracheal cytotoxin (TCT), Adenylate cyclase toxin (AC)

Bordetella pertussis: what cells are destroyed with what effect

Ciliated cells are destroyed, leaving a denuded mucosa without protective and functioning cilia

Bordetella pertussis: why does the body resort to severe coughing

in an attempt to clear damage, excess mucous, and debris

Bordetella pertussis: incubation period

7-10 days prior to symptom onset

Bordetella pertussis: 3 disease stages

Catarrhal, paroxysmal, convalescent

Bordetella pertussis: catarrhal stage

Non-specific cold-like symptoms develop ~1 week after infection

Bordetella pertussis: paroxysmal stage

Peak coughing; worsen symptoms due to progressively thickened mucus and damaged respiratory epithelium; inspiratory whoop

Coughing can lead to broken ribs, loss of bladder control, and blue lips

Bordetella pertussis: convalescent phase

pertussis symptoms gradually fade; secondary pneumonia possible

Bordetella pertussis: 4 methods of diagnosis

Pertussis symptoms usually diagnostic (Coughing paroxysms, inspiratory "whoop," or post-paroxysm vomiting, all second stage)

Isolation of B. pertussis from clinical specimen (Catarrhal stage)

Positive NAAT (polymerase chain reaction (PCR)) for B. pertussis

Contact with a laboratory-confirmed case of pertussis

Bordetella pertussis: treatment

Early antibiotic treatment critical (decreased complications and spread)

Supportive care (humidifier, hydration, etc.)

Hospitalization may be required (infants/young children, compromised, elderly)

• Fatal in 20% of children under 5 years old and adults over 40 years old

Bordetella pertussis: first vaccine introduced

High efficacy when 1st introduced in DTP vaccine in 1940s

Original formulation was whole cell suspension

Long lasting protection infancy thru adulthood

High rate of mild side effects

Bordetella pertussis: current vaccine

Replaced in mid 1990s with acellular versions (DTaP, Tdap) due to parental pressure

Less effective, multiple boosters necessary

Immunity wanes with age

Pertussis cases increased