1. Rickettsias, Chlamydias, Spirochetes, and Vibrios21
Rickettsias, Chlamydias, Spirochetes, and Vibrios

2. Rickettsias Extremely small
Appear almost wall-less due to small amount of peptidoglycan present
Obligate intracellular parasites
Unusual since they have functional genes for protein synthesis, ATP production, and reproduction
Four genera cause disease in humans:
Rickettsia, Orientia, Ehrlichia, and Anaplasma

3. Rickettsias Rickettsia Nonmotile, aerobic bacteria
Transmitted via arthropod vectors
Bacteria live in the cytosol of host cell
Three species cause most human infections:
R. rickettsii
R. prowazekii
R. typhi

4. Rickettsias Rickettsia Rickettsia rickettsii
Rocky Mountain spotted fever
Most severe and common rickettsial illness
Hard ticks transmit among humans and rodents
Most infected individuals develop rash on trunk and appendages
Approximately 5% of patients die
Treated with antimicrobials
Prevention involves avoiding ticks

5. Cases of Rocky Mountain spotted fever in the United States, 2002–2014.
Disease in Depth 21.1 (3 of 10)
Cases of Rocky Mountain
spotted fever in the United
States, 2002–2014.
1–400
401–800
801–1200
1201–1600
1601–2000
>2000

6. ROCKY MOUNTAIN SPOTTED FEVER DISEASE IN DEPTH PATHOGENESIS
Slide 1
DISEASE
IN DEPTH
ROCKY MOUNTAIN
SPOTTED FEVER
Rickettsia
INSIDE BLOOD VESSEL
INSIDE BLOOD VESSEL
R. rickettsi
escaping
into cytosol
PATHOGENESIS
Endothelial cells
lining small
blood vessel
Endosome
Rickettsias divide every 8–12
hours in the host cell's cytosol. Daughter
rickettsias escape from long cytoplasmic
extensions of the host cell and infect
other endothelial cells.
Engorged
Dermacentor
R. rickettsi triggers
endocytosis by cells lining
blood vessels (endothelium);
then it lyses the endosome’s
membrane, escaping into the
cytosol.
Infected tick introduces R. rickettsii
in its saliva. This occurs only after the
tick has fed for at least six hours. Active
bacteria are released into the mammalian host’s circulatory system.

7. ROCKY MOUNTAIN SPOTTED FEVER DISEASE IN DEPTH PATHOGENESIS
Slide 2
DISEASE
IN DEPTH
ROCKY MOUNTAIN
SPOTTED FEVER
Rickettsia
PATHOGENESIS
Endothelial cells
lining small
blood vessel
Engorged
Dermacentor
Infected tick introduces R. rickettsii
in its saliva. This occurs only after the
tick has fed for at least six hours. Active
bacteria are released into the mammalian
host’s circulatory system.

8. ROCKY MOUNTAIN SPOTTED FEVER DISEASE IN DEPTH PATHOGENESIS
Slide 3
DISEASE
IN DEPTH
ROCKY MOUNTAIN
SPOTTED FEVER
Rickettsia
INSIDE BLOOD VESSEL
R. rickettsi
escaping
into cytosol
PATHOGENESIS
Endothelial cells
lining small
blood vessel
Endosome
Engorged
Dermacentor
R. rickettsi triggers
endocytosis by cells lining
blood vessels (endothelium);
then it lyses the endosome’s
membrane, escaping into the
cytosol.
Infected tick introduces R. rickettsii
in its saliva. This occurs only after the
tick has fed for at least six hours. Active
bacteria are released into the mammalian
host’s circulatory system.

9. ROCKY MOUNTAIN SPOTTED FEVER DISEASE IN DEPTH PATHOGENESIS
Slide 4
DISEASE
IN DEPTH
ROCKY MOUNTAIN
SPOTTED FEVER
Rickettsia
INSIDE BLOOD VESSEL
INSIDE BLOOD VESSEL
R. rickettsi
escaping
into cytosol
PATHOGENESIS
Endothelial cells
lining small
blood vessel
Endosome
Rickettsias divide every 8–12
hours in the host cell's cytosol. Daughter
rickettsias escape from long cytoplasmic
extensions of the host cell and infect
other endothelial cells.
Engorged
Dermacentor
R. rickettsi triggers
endocytosis by cells lining
blood vessels (endothelium);
then it lyses the endosome’s
membrane, escaping into the
cytosol.
Infected tick introduces R. rickettsii
in its saliva. This occurs only after the
tick has fed for at least six hours. Active
bacteria are released into the mammalian
host’s circulatory system.

10. Disease in Depth 21.1
Slide 5
R. rickettsii secretes no toxins, and disease is not the
product of immune response. Apparently, damage to the
endothelial cells leads to leakage of blood into the tissues,
which results in low blood pressure and insufficient
nutrient and oxygen delivery to the body’s organs.
Blood leaks
into tissue

11. Disease in Depth 21.1
Slide 6
R. rickettsii secretes no toxins, and disease is not the
product of immune response. Apparently, damage to the
endothelial cells leads to leakage of blood into the tissues,
which results in low blood pressure and insufficient
nutrient and oxygen delivery to the body’s organs.
Blood leaks
into tissue
R. rickettsii escaping an endothelial
cell

12. Disease in Depth 21.1
Slide 7
R. rickettsii secretes no toxins, and disease is not the
product of immune response. Apparently, damage to the
endothelial cells leads to leakage of blood into the tissues,
which results in low blood pressure and insufficient
nutrient and oxygen delivery to the body’s organs.
Blood leaks
into tissue
Subcutaneous hemorrhages (petechiae) of
RMSF patient

13. Disease in Depth 21.1
Slide 8
R. rickettsii secretes no toxins, and disease is not the
product of immune response. Apparently, damage to the
endothelial cells leads to leakage of blood into the tissues,
which results in low blood pressure and insufficient
nutrient and oxygen delivery to the body’s organs.
Blood leaks
into tissue
R. rickettsii escaping an endothelial
cell
Subcutaneous hemorrhages (petechiae) of
RMSF patient

14. The Nature of Infectious Disease
Dr. Bauman's Microbiology Video Tutor
For more information, listen to the Disease in Depth video tutor on Rocky Mountain spotted fever.

15. Rickettsias Rickettsia Rickettsia prowazekii Epidemic typhus
Causes high fever, depression, and rash
Human body louse transmits bacteria to humans
Humans are the primary host
Occurs in crowded, unsanitary conditions
Prevalent in Africa, Central and South America, and China
Treat with doxycycline or chloramphenicol
Prevent with good personal hygiene
Vaccine available for high-risk populations

16. Rickettsias Rickettsia Rickettsia typhi Murine typhus
Causes fever, headache, chills, muscle pain, and nausea
Rodents are the major reservoir
Fleas transmit bacteria among animal hosts and humans
Disease is not usually fatal
Most often seen in southern United States
Endemic in every continent except Antarctica
Treat with doxycycline
Prevent by avoiding the arthropod vectors

17. Rickettsias Orientia tsutsugamushi
Formerly classified in the genus Rickettsia
Mites are the reservoir and vector of Orientia
Transmit bacterium to offspring by transovarian transmission
Transmit bacterium among rodents and humans
Scrub typhus
Causes fever, headache, muscle pain, and sometimes a rash
Endemic to eastern Asia, Australia, and India
Occurs in U.S. among immigrants from endemic areas
Treat with appropriate antimicrobials
Prevent by avoiding exposure to mites

18. Rickettsias Ehrlichia and Anaplasma
Causes two emerging diseases in the United States:
Ehrlichia chaffeensis
Human monocytic ehrlichiosis
Anaplasma phagocytophilum
Anaplasmosis
Both resemble Rocky Mountain spotted fever without the rash
Ticks transmit these bacteria
Three developmental stages in leukocytes:
Elementary body, initial body, and morula
Immediate treatment with antimicrobials to prevent complications
Prevent by avoiding ticks

19. Entry Elementary body in phagosome Nucleus Initial body Morula
Figure The growth and reproduction cycle of Ehrlichia and Anaplasma in an infected leukocyte.
Entry
Elementary body
in phagosome
Nucleus
Initial
body
Morula
containing
many
rickettsias
Release of
rickettsias

20. Figure The geographical distribution of ehrlichiosis and anaplasmosis in the United States (as of 2014). NN NN NN NN NN NN NN NN NN

21. Table 21.1 Characteristics of Some Rickettsias

22. Chlamydias Once considered to be viruses Do not have cell walls
Have two membranes without any peptidoglycan between them
Grow and multiply only within the vesicles of host cells
Have a unique developmental cycle involving two forms
Elementary bodies (EBs) and reticulate bodies (RBs)
Both forms can occur within the phagosome of a host cell

23. Figure 21.3 Development of chlamydias.
Elementary body (EB)
attaches to receptor
on host cell
(0 hour).
EB triggers its
own endocytosis
by host cell.
EBs are released
from host cell
(40 hours).
Vesicle
Reticulate body (RB)
Elementary body (EB)
Inclusion body
Most RBs convert back
into EBs (21 hours).
EB inside
endocytic
vesicle.
EB converts
into reticulate
body (RB)
within vesicle
(10 hours).
RB divides rapidly,
resulting in multiple
RBs. The vesicle is
now called an
inclusion body.
Inclusion
body

24. Chlamydias Chlamydia trachomatis Pathogenesis and Epidemiology
Has a limited host range
One strain infects mice; all others infect humans
Enters the body through abrasions and lacerations
Infects the conjunctiva and various mucous membranes
Most common reportable sexually transmitted disease in U.S.
Clinical manifestations due to cell destruction and inflammation
Also a major cause of eye infections worldwide
Endemic in poor communities without adequate personal hygiene, sanitation, or medical care

25. Chlamydias Chlamydia trachomatis Diseases
Sexually transmitted diseases
Lymphogranuloma venereum
Initial genital lesion is followed by formation of buboes
Buboes may enlarge and rupture producing draining sores
Most infections in women are asymptomatic
Reinfection may cause pelvic inflammatory disease
Nongonococcal urethritis
Proctitis

26. Figure 21.4 An advanced case of lymphogranuloma venereum in a man.

27. Chlamydias Chlamydia trachomatis Diseases Trachoma Ocular disease
Leading cause of nontraumatic blindness in humans
Scarring of the conjunctiva causes the eyelashes to turn
Causes corneal abrasions that lead to blindness
Infection typically occurs during childbirth

28. Figure 21.5 The underside of an eyelid afflicted with trachoma.

29. Chlamydias Chlamydia trachomatis Diagnosis, Treatment, and Prevention
Demonstrate bacteria inside cells from the site of infection
Treatment
Antibiotics can be administered for genital and ocular infections
Surgical correction of deformities from trachoma may prevent blindness
Prevention
Abstinence to prevent sexually transmitted infections
Blindness prevented with prompt use of antibacterial agents

30. Figure 21.6 A direct fluorescent antibody test for Chlamydia trachomatis.

31. Chlamydias Chlamydophila pneumoniae
Causes bronchitis, pneumonia, and sinusitis
Most infections only produce malaise and a chronic cough
Severe cases can resemble primary atypical pneumonia caused by Mycoplasma pneumoniae
Treat with doxycycline or azithromycin
Some infections persist despite treatment
Prevention is difficult because C. pneumoniae is ubiquitous

32. Chlamydias Chlamydia psittaci Ornithosis
Disease of bird that can be transmitted to humans
Usually causes flulike symptoms
Rarely nonrespiratory conditions are observed
Individuals who handle animals are at greatest risk of infection
Transmitted via inhalation of aerosols or contact with infected material or a pet bird
Diagnosis difficult, since symptoms similar to other respiratory infections
Treat with tetracycline or azithromycin
Prevention involves proper handling of birds

33. Table 21.2 Characteristics of the Smallest Microbes

34. Spirochetes Thin, tightly coiled, helically shaped bacteria
Moves in a corkscrew fashion through its environment
Due to rotation of axial filaments
Enables pathogenic spirochetes to burrow through hosts' tissues
Three genera cause human disease:
Treponema, Borrelia, and Leptospira

35. Spirochetes Treponema Treponema pallidum pallidum
Pathogenicity and Epidemiology
Pathogen of humans only
Most widespread Treponema strain
Causative agent of syphilis
Syphilis occurs worldwide
Transmission is almost solely via sexual contact
Endemic among sex workers, men who have sex with men, and users of illegal drugs

36. Figure 21.7 Spirochetes of Treponema pallidum pallidum.

37. Figure 21.8 The incidence of adult syphilis in the United States.5 4
Cases (per 100,000) 3 70 2 60 1 50 40
'03
'04
'05
'06
'07
'08
'09
'10
'11
'12
'13
'14
Reported cases per 100,000 population 30 20 10
'45
'50
'55
'60
'65
'70
'75
'80
'85
'90
'95
'00
'05
'10
'15
Year
≤0.2
0.21–2.2
>2.2

38. Spirochetes Treponema Treponema pallidum pallidum Disease
Untreated syphilis has four phases:
Primary, secondary, latent, and tertiary
Congenital syphilis
An infected mother can transmit Treponema to her fetus
Can result in fetal death or mental retardation and malformation

39. Figure 21.9 The lesions of syphilis.

40. Spirochetes Treponema Treponema pallidum pallidum
Diagnosis, Treatment, and Prevention
Diagnosis
Antibody tests against bacterial antigens
Tertiary syphilis is difficult to diagnose
Treatment
Penicillin is the drug of choice
Ineffective against tertiary syphilis
Prevention
Abstinence and safe sex

41. Spirochetes Treponema Nonvenereal Treponemal Diseases
Primarily seen in impoverished children in unsanitary conditions
T. pallidum endemicum
Bejel
T. pallidum pertenue
Yaws
T. carateum
Pinta
Cause skin lesions
Penicillin used to treat these diseases
Prevent by limiting contact with skin lesions

42. Figure Yaws.

43. Spirochetes Borrelia Lightly staining, spirochetes
Cause two diseases in humans:
Lyme disease
Relapsing fever

44. Spirochetes Borrelia Lyme Disease
Borrelia burgdorferi is the causative agent
Lacks iron-containing enzymes and proteins
Bacteria are transmitted to humans via a tick bite
Hard ticks of the genus Ixodes are the vectors
Tick life cycle important in understanding spread of Lyme disease

45. Figure 21.11 Borrelia burgdorferi.
Red blood cell

46. Figure 21.12 The life cycle of the deer tick Ixodes and its role as the vector of Lyme disease.
Uninfected, 6-legged tick larvae hatch
from egg, crawl up vegetation, and
wait to jump on passing animal.
Spring
(Year 1)
Larvae
Spring
(Year 2)
Tick larvae become
infected with Borrelia
when they feed on
small mammals or birds.
After feeding for 3–4
days, they drop off.
Infected nymphs
feed on animals or
humans, introducing
Borrelia (year 2).
Larvae develop
into 8-legged
nymphs that
remain infected.
Female ticks lay
uninfected eggs
in fall (year 2).
Summer
Nymph
Nymphs develop
into adult ticks
over the summer
(year 2).
Adult ticks feed
on deer or other
animals and mate
in fall (year 2).
Borrelia
multiplies in
infected larvae.
Winter
Fall

47. Spirochetes Borrelia Lyme Disease
Shows a broad range of signs and symptoms
Three phases of disease in untreated patients:
Expanding red "bull's-eye" rash occurs at infection site
Neurological symptoms and cardiac dysfunction
Severe arthritis that can last for years
Result of the body's immune response
Increase of cases in the United States
Humans in closer association with Borrelia-infected deer ticks

48. Figure 21.13 The occurrence of Lyme disease in the United States.38 36 34 32 30 28 26 24 22 20
Cases (thousands) 18 16 14 12 10 8 6 4 2
1990
1995
2000
2005
2010
2015
Year
1 dot placed randomly within county
of residence for each confirmed case

49. Lyme Disease Pathology
Borrelia
Lyme Disease
Diagnosis based on signs and symptoms and serological tests
Antimicrobial drugs effectively treat first stage of Lyme disease
Treatment of later stages difficult
Symptoms primarily result from the immune response
Prevention is best achieved by avoiding ticks

50. Spirochetes Borrelia Relapsing Fever
Louse-borne relapsing fever
Borrelia recurrentis is the causative agent
Transmitted to humans by the human body louse
Occurs in Africa and South America
Tick-borne relapsing fever
Several Borrelia species can cause this disease
Transmitted to humans by soft ticks
Occurs worldwide
Characterized by recurring episodes of septicemia and fever
Due to body's repeated efforts to remove the spirochetes

51. Days following infection
Figure The time course of recurring episodes of fever in relapsing fevers.
Second
antibody
response
Third
antibody
response
Second
antigenic
challenge
Third
antigenic
challenge
First
antigenic
challenge
First
antibody
response 41 40 39
Body temperature (°C) 38 37 8 10 12 14 16 18 20 22 24 26
Days following infection

52. Spirochetes Borrelia Relapsing Fever
Observation of spirochetes is the primary method of diagnosis
Successful treatment is with antimicrobial drugs
Preventive measures
Avoidance of ticks and lice
Good personal hygiene
Use of chemical repellents

53. Spirochetes Leptospira Leptospira interrogans
Motile, obligately aerobic bacteria
Found in numerous wild and domestic animals
Leptospirosis
Leptospira enters through the skin or mucous membranes
Travels via the bloodstream throughout the body
Can cause hemorrhaging and liver and kidney dysfunction
Occurs worldwide
Treat with intravenous penicillin
Eradication impractical due to the various animal reservoirs
Vaccine available for livestock and pets

54. Figure 21.15 Leptospira interrogans.

55. Pathogenic Gram-Negative Vibrios
Shares many characteristics with enteric bacteria
Found in water environments worldwide

56. Figure 21.16 Vibrio cholerae.
Curved rods

57. Pathogenic Gram-Negative Vibrios
Pathogenesis, Epidemiology, and Disease
Common species to infect humans
Bacteria can survive in freshwater
Cholera
Humans infected by ingesting contaminated food and water
Found most in areas with poor sewage and water treatment
"Rice-water stool" is characteristic
Most important virulence factor is cholera toxin
Causes severe loss of fluid and electrolytes
High mortality if left untreated

58. Figure 21.17 The spread of cholera in the Americas during the most recent pandemic.
Initial epidemic
January 1991
August 1991
February 1992
November 1994
Second wave epidemic
October 2010
January 2011
January 2013

59. Figure 21.18 The action of cholera toxin in intestinal epithelial cells.
Intestinal lumen A
Cholera toxin
binds to
membrane
of epithelial
cell.
Water follows
electrolytes into
lumen. B
H2O
Cl–
Na+
Na+
Cl–
Epithelial cell
Portion
of toxin
(part of A)
enters cell.
Cyclic AMP
stimulates
cell to secrete
Cl–, Na+,
and other
electrolytes. A1
cAMP
A1 activates
adenylate
cyclase (AC). AC
Cyclic AMP
(cAMP) is
synthesized.
ATP

60. Pathogenic Gram-Negative Vibrios
Diagnosis, Treatment, and Prevention
Diagnosis
Usually based on characteristic diarrhea
Treatment
Fluid and electrolyte replacement
Antimicrobial drugs can reduce exotoxin production and the volume of diarrhea
Prevention
Proper sewage and water treatment can prevent epidemics
Oral vaccine provides some protection

61. Pathogenic Gram-Negative Vibrios
Other Diseases of Vibrio
V. parahaemolyticus
Results from ingestion of shellfish
Causes cholera-like gastroenteritis
V. vulnificus
Septicemia
Due to consumption of contaminated shellfish
Wound infections
Due to washing wounds with contaminated seawater
Infections can be fatal if untreated

62. Pathogenic Gram-Negative Vibrios
Campylobacter jejuni
Likely most common cause of gastroenteritis in the United States
Many animals serve as reservoirs for the bacteria
Humans infected by consuming contaminated food, milk, or water
Poultry is the most common source of infection
Infections produce self-limiting bloody and frequent diarrhea
Proper food handling and preparation can reduce spread of bacteria

63. Pathogenic Gram-Negative Vibrios
Helicobacter pylori
Slightly helical, motile bacterium
Colonizes stomach of its hosts
Ingestion of bacteria from contaminated hands, well water, or fomites
Causes gastritis and most peptic ulcers
Numerous virulence factors enable it to colonize the stomach
Proteins that inhibit production of stomach acid
Flagella help the bacteria burrow through the stomach lining
Adhesins facilitate binding to gastric cells
Enzymes that help neutralize stomach acid

64. Figure 21.19 Helicobacter pylori.

65. Figure 21.20 The role of Helicobacter pylori in the formation of peptic ulcers.
(neutralizes stomach
acid)
Layer of mucus
Acidic gastric juice
Nucleus
Epithelial cell
in stomach lining
Mucus-
secreting cell
Neutrophil
Lymphocyte
Ulcer
Bacteria invade mucus and attach to
gastric epithelial cells.
Helicobacter, its toxins, and inflammation
cause the layer of mucus to become thin.
Gastric acid destroys epithelial cells and
underlying tissue.

66. Pathogenic Gram-Negative Vibrios
Helicobacter pylori
Presence of H. pylori can be demonstrated by positive urease test
Biochemical tests provide a definitive identification
Treat with antimicrobial drugs and drugs that inhibit acid production
Prevention
Good hygiene
Adequate sewage treatment
Proper food handling