9

Question 1

Small Gram-negative Pathogens

Answer 1

Chlamydiae
Rickettsiae
Ehrlichia

Question 2

Chlamydiae size

Answer 2

Small (.25 µm - .8 µm)
Just at limit of light microscopy
Similar in size to some viruses

Question 3

Chlamydiae gram

Answer 3

negative

LPS outer membrane and cytoplasmic membrane

Question 4

Chlamydiae No

Answer 4

peptidoglycan (murein) in cell walls

Genes are present
Structure analogous to murein can be seen by EM

Question 5

Chlamydiae Obligate

Answer 5

intracellular pathogens
Grow only inside cells or on live tissues
Humans, animals, insects, protozoa
Small genomes (1 – 1.2 megabases

Question 6

Chlamydiae description

Answer 6

“Energy parasites”
Depend on host for ATP
Auxotrophic for some amino acids

Question 7

Chlamydia 4 species

Answer 7

C. trachomatis
-3 Biovars
-Multiple strains in each
C. pneumoniae
First 2 = human

C. psittaci
C. pecorum
Primarily animal, but can infect humans.

Question 8

Chlamydial Infections (In General)

Answer 8

Leading cause of preventable blindness in the world

The most common agents of sexually transmitted bacterial infections

Speculation that every living adult has had pneumonia (“walking”) caused by C. pneumoniae

Droplet or direct contact infection

Infect mucosal epithelial cells

Localized (usually – LGV is invasive)
Eyes, lungs, genitalia

Spread by the 4 Fs
Fingers
Flies
Fomites
Fornication

Question 9

C. trachomatis Infections

Answer 9

Genital tract infections
Men – Prostititis, epididymitis
Women – Cervicitis, PID, premature births, pelvic pain, newborn eye/lung infections
Both – Urethritis, infertility, proctitis, arthritis,

Usually asymptomatic in females
Chronic and repeat infections can cause sterility and/or ectopic pregnancy

Infections may be acute or chronic
Silent period – organisms location unknown

Asymptomatic carriage results in most damage and scarring

During birth, infants can contract an infection, leading to conjuctivitis and pneumonia

Question 10

Extracellular

Answer 10

Elementary body (EB) transit form

Question 11

Entry of EBs into epithelial cells

Answer 11

Masquerade as nutrients, growth factors, hormones to bind to specific receptors

Question 12

EB modify the endocytic vesicle in two ways:

Answer 12

Maintain pH above 6.2

Prevents vesicle from fusion with lysosomes

Question 13

Vesicle is also modified with host components

Answer 13

(glycolipids) for camouflage

Question 14

Infectious EB change into larger intracellular active organisms (RB)

Answer 14

Synthesize molecules using host metabolites and energy

Divide by binary fission

Question 15

RB Nutrient Uptake

Answer 15

Tube-like structures (“drinking straws”) that allow them to feed on the eukaryotic host cell without leaving the inclusion vacuole
18 – 23 hollow tubes that protrude from bacterial cell cytoplasm into host cell cytoplasm

Question 16

Trachoma (C. trachomitis strains)

Answer 16

Inflammation of the conjuctiva, can cause blindness, scarring of cornea
Spread by direct contact with eye, nose, and throat secretions from affected individuals, or contact with objects, such as towels and/or washcloths

Question 17

Lymphogranuloma venerum

Answer 17

STD
Systemic, invasive infection apparent in the lymph nodes that drain the genital tract
Predominately in developing countries
Rare in U.S. (200 – 400 cases)
More common in Africa, Asia, India, South America

Question 18

Chlamydophila pneumoniae

Answer 18

Perhaps the most prevalent chlamydial pathogen in the human population

50% of people up to the age of 20 have been infected, 80% of older adults

Usually asymptomatic or acute respiratory response, but chronic respiratory infections have been associated with asthma, CF, lung cancer

Can be directly observed in 40 - 100% of patients with atherosclerotic heart lesions

Question 19

Treatment - Chlamydophila pneumoniae

Answer 19

Metabolic active RB forms are targets of antimicrobials

Four membrane layers to penetrate:
Host cell plasma membrane
Inclusion membrane
Chlamydial outer membrane
Chlamydial cytoplasmic membrane

Organisms grow slow
Antibiotics must be maintained for long periods

Question 20

Rickettsiae

Answer 20

Small Gram negative rods
Don’t stain well

Obligate intracellular bacteria

Zoonoses - infections transmitted from animals to humans

Question 21

Rickettsiae not

Answer 21

energy parasites like the Chlamydiae
Can synthesize some of their own ATP and are capable of independent metabolism

May lack certain metabolites necessary for growth
No flagella or endospores
Must be cultivated in animals, embryonated eggs, or cell cultures in the lab

Question 22

Rickettsiae Transmission

Answer 22

Only members of the hard tick family Ixodidae are naturally infected with Rocky Mountain spotted fever

Question 23

Spread and Multiplication Rickettsiae

Answer 23

Attach to vascular endothelial cells (small blood vessels)
Induce endocytosis
Once inside, presumably lyse the phagosome (phospholipase) and enter the cytosol

Question 24

Spread, Multiplication, Damage

Answer 24

Mode of exit from host cell varies
R. prowazekii exits by cell lysis
R. rickettsii get extruded from the cell through local projections (filopodia)
Actin in the host cell associates with R. rickettsii and the actin helps to “push” the bacteria through the filopodia
R. tsutsugamushi exits by budding through the cell membrane
Remains enveloped in the host cell membrane as it infects other cells

Question 25

Injury to the host Rickettsiae

Answer 25

Proportional to the number of intracellular bacteria Lysis of the cells results in leakage of blood (rash) Hemorrhagic spots Organism can travel to other vessels including the heart and brain 75% of patients will clear the infection, even before antimicrobial treatment

Question 26

R. prowazekii

Answer 26

Typhus fever Recrudescent typhus - reactivation of the dormant agent seen in U.S. Transmitted by human lice Improved sanitary conditions lead to lowered incidence Reservoir is humans and flying squirrels

Question 27

R. typhi

Answer 27

More prevalent and widespread Murine typhus Transmitted by rats and rat fleas

Question 28

Orientia (formerly Rickettsia) tsutsugamushi

Answer 28

Scrub typhus Variety of antigenic types NO RASH as observed in others

Question 29

Ehrlichia

Answer 29

``` Discovered 1987 E. chaffeensis and E. ewingii Obligate intracellular bacteria Transmitted by Lone Star tick Infects mostly monocytes and macrophages Human granulocytic ehrlichiosis (HGE) and human monocytic ehrlichiosis (HME) Fever, malaise, headache and myalgia Develop within host cell vacuoles first as reticulate cells (RC) and then as dense-core cells (DC) ```

Question 30

Diagnosis of Rickettsioses

Answer 30

``` Problematic During first visit, patients don’t typically have fever or rash, and may not be aware of a tick bite Requires eukaryotic cell cultures or inoculation of animals Handling is notoriously hazardous Clinical diagnostic tests Antibody titers Fluorescent antibody assay Complement fixation Latex agglutination ```

Question 31

Mycoplasma

Answer 31

``` Smallest organisms capable of growth on cell-free media Requires sterol (cholesterol) Characteristic “fried egg” appearance Small colonies Slow growth ``` Lack a cell wall (no murein) Not sensitive to penicillin Cell membranes contain sterols Found in other mammals and in birds

Question 32

Four Species Cause Disease

Answer 32

M. pneumoniae Prototype mycoplasma Primary atypical pneumonia M. genitalium, M. hominis, Ureaplasma urealyticum Genitourinary tract infections Some mycoplasmas are part of the normal human oral flora

Question 33

M. pneumoniae: Encounter and Entry

Answer 33

Humans only reservoir Unlike pneumococci, prolonged asymptomatic colonization is uncommon Infections mild and moderately contagious Spread through close-contact groups Passed by respiratory droplets “Walking pneumonia” Primary atypical pneumonia – not cleared by penicillin Adhere to respiratory epithelium Terminal adhesion structures – tip-mediated attachment organelle

Question 34

Spread, Multiplication, and Damage

Answer 34

Main cells of the inflammatory response are lymphocytes Unusual Largely limited to the respiratory mucosa that lines the airways Doesn’t get into the lung alveoli Bronchopneumonia Not highly destructive of tissues, but ciliary function is impaired Tissue toxic substances, may include H2O2 Inflammatory mediators

Question 35

Hemolytic anemia

Answer 35

IgM = cold hemagglutinins At lower temperatures, these antibodies cause RBCs to stick together Detectable in 50% of cases Clinically significant hemolysis is rare

Question 36

M. genitalium – newest emerging human pathogen

Answer 36

Urethritis, cervicitis, endometritis, PID Isolated from synovial and respiratory fluids A lot like M. pneumoniae M. hominis and U. urealyticum frequently associated with diseases in newborns (commonly found in the respiratory and genitourinary tracts) Present in most of the sexually active population Can be isolated from the spinal fluid of newborns, don’t always cause disease