7322 B1 Flashcards
Obligate intracellular organisms
Cannot live outside a living cell
Prokaryotes
- 1 chromosome
- Circular DNA
- Mono- or polycistronic (messenger RNA can encode for one polypeptide or many polypeptides)
- No nucleus
- No membrane organelles
- 70s ribosomes (30 + 50_
- Binary fission
Eukaryotes
- 1 chromosome, linear DNA with histones
- Monocistronic
- Exon and introns
- Nucleus
- Membrane organelles
- Mitosis with cytokinesis
Gram (+) Positive
- 2 Layers
- inner cytoplasm membrane
- outer thick peptidoglycan layer
- No lipid content
- No endotoxin (LPS)
- No periplasmic space
- Vulnerable to lysozyme and penicillin attack
Gram (-) Negative
- 3 Layers
- Inner cytoplasmic layer
- Thin peptidoglycan layer
- Outer membrane with lipopolysaccharide (LPS)
- High lipid content
- Endotoxin (LPS)
- Periplasmic space
- Porin channel
- Resistant to lysozyme and penicillin attack
Cocci
-Spherical
Bacilli
- Rods
* short rods are called coccobacilli
Spiral Forms
- Comma
- Spiral
Pleomorphic
-No distinct shape
Gram (+) positive
3 Cocci?
4 Bacilli?
- Cocci
- Streptococcus (chains)
- Enterococcus (chains)
- Staphylococcus (clusters)
- Bacilli
- Bacillus (spores)
- Clostridium (spores)
- Corynebacterium (No spores)
- Listeria (No Spores)
Gram (-) negative
2 Cocci?
1 Spiral?
1 Comma?
- Cocci
- Neisseria (diplococci)
- Moraxella (diplococci)
- Spiral
- Spirochetes (too small to see)
- Comma
- Vibrio cholerae
REMAINING GRAM NEGATIVE ARE EITHER RODS OR PLEOMORPHIC
Neither Gram (+) or (-)
- Mycobacteria (Acid Fast)
- Mycoplasm (No cell wall)
Catalase?
Peroxidase?
Superoxide Dismutase?
Catalase - Breaks down hydrogen peroxide to water and oxygen
Peroxidase - Breaks down hydrogen peroxide to water and oxygen
Superoxide Dismutase - Breaks down superoxide radicals
Obligate Aerobes
- Use glycolysis with oxygen as the final electron acceptor
- Have Catalase, Peroxidase and Superoxide dismutase
- NEED oxygen to survive
Facultative anaerobes
- Aerobic bacteria that can grow in the absence of oxygen
- Have catalase and superoxide dismutase
- Can use fermentation as a source of energy, as well as glycolysis
Microaerophilic
- Use fermentation only
- Can tolerate low amounts of oxygen due to Superoxide dismutase
Obligate Anaerobe
- Use fermentation only
- Cannot tolerate any oxygen due to the absence of enzymes
Pathogenicity
refers to the ability of an organism to cause disease
Virulence
Often used interchangeably with pathogenicity, it refers to the degree of pathology caused by the organism
Avirulent
does not cause disease
Virulence factors
a structure, toxin, adhesion, etc… that contributes to the ability of a pathogen to cause disease
Adhesion factors
- Involved in the binding and initial interactions between pathogen and host cells.
- Can be proteins in cell walls or membranes, or structures such as pili/fimbriae
- Antigenic variation can aid in the persistence of infection (evade host response - surface proteins of bacteria can alter in such a way that it is not recognized by the immune system)
Multi-layer of endospores
- Cell membrane
- Thick peptidoglycan layer
- Another cell membrane
- Wall of keratin-like protein
- Outer layer called exosporium
Facultative intracellular organism
Like to live in the host cell
Endotoxins
-Part of outer membrane
-Part of LPS of Gram (-) bacteria
*Listeria monocytogenes, only gram (+) with endotoxin
NOTE:
Sometimes treating patients with gram-negative infection can worsen disease as bacteria are lysed.
Endotoxins act on…
- Some act outside the host cell (TSST)
- Some act on cell membrane
- Some act inside the cell
Bacteremia
bacteria in the blood
Sepsis
refers to bacteremia that causes systemic immune response to infection
Septic shock
caused by gram (-) and gram (+) bacteria
High mortality (40%)
Drop in blood pressure
TNF triggers coagulation causing vasodilation
What type of gene transfer are naked DNA fragments are taken up?
Transformation
Two types of Phage dependant gene transfer are?
Generalized and Specialized
What type of gene transfer involves a sex pilus and plasmid?
Conjugation
What are mobile genetic elements that insert into chromosome?
Transposons (Jumping genes)
Naked DNA from a lysed bacterium is picked up by another bacterium
Transformation
Recipient bacteria must be competent (able to bind and internalize DNA)
Bacterial Benefits of Capsule
- Both Gram (+) and (-) have them
- Interferes with phagocytosis
- Impairs complement killing
Defense against Capsules
-Vaccines target capsule
-Illicit IgG antibody response which helps macrophage kill bacteria
NOTE
Some vaccines are comprised of serotypes of capsular polysaccharides
Facultative intracellular organisms often inhibit phagosome-lysosome fusion in macrophages. They also avoid effects of the host cell’s release of superoxide and hydrogen peroxide. What are some organisms in this class?
- Listeria monocytogenes
- Solmonella typhi
- Yersinia
- Francisella tularensis
- Brucella
- Legionella
- Mycobacteria
- Noardia
Flagella
- Spin and cause the bacteria to move
- Provides strong motility, enables penetration of mucus layer
Pilli (Fimbrae)
- Straight filaments arising from the cell wall
- short
- Can serve as adherence factors
- specialized pili (sex) are involved in gene transfer
What are the two major types of toxins?
Endotoxin
Exotoxin
Exotoxins are:
Proteins released by bacteria
- Some act on inside the cell
- Binding unit (B or H)
- translocating unit (A or L)
- Some act outside the host cell
- Some act on cell membrane
Endotoxins are:
Part of the outer membrane
- part of lipopolysaccharide (LPS) of gram (-) bacteria
- The lipid A portion of LPS is the toxic component
- Sometimes treating patients with antibiotics who have gram (-) infections can worsen the disease as lysed bacteria release large amounts of endotoxin
- ONLY GRAM (+) WITH ENDOTOXIN IS
- Listeria monocytogenes*
Bacteremia
bacteria in the blood
Sepsis
refers to bacteremia that causes a systemic immune response to infection
Septic shock
Caused by gram (-) and gram (+) bacteria
- Endotoxin (LPS) is often the stimulus of septic shock
- Dangerous drop in blood pressure and multi-organ failure
- High mortality (about 40%)
Transformation
Naked DNA from lysed bacteria is picked up by another bacteria
- recipient bacteria must be competent (able to bind and internalize)
- internalized DNA is incorporated into bacterial genome (must have homology)
Associated with burns, diabetic lesions, lungs in CF patients and also Catheters and artificial hips.
BioFilms
-an extracellular polysaccharide network that protects bacteria from antibiotics and immune response.
Streptococci are gram (+) and…
-Found in chains and catalase negative (cannot breakdown hydrogen peroxide to oxygen and water)
-Can be classified by their ability to hemolyze RBC
and antigenic characteristics of carbs in cell wall
*Letter given to different Lancefield antigens
Staphylococci are gram (+) and …
-Found in clusters (Grapes) and are catalase positive
Lancefield antigen A
-Group A streptococci
Streptococcus Pyogenes
- Cause
- Strep throat
- Scarlet fever
- Skin infections
- Streptococcal toxic shock syndrome
- Streptococcal glomerulonephritis
Non-Lancefield type
Lancet shaped Gram (+) cocci found in pairs (diplococci)
Streptococcus pneumoniae
- The major cause of pneumonia and meningitis
- otitis media (middle ear infection) in children
- The major virulence factor is the polysaccharide capsule
- Vaccines are created to target capsule
Group B Streptococci
Streptococcus agalactiae cause…
neonatal meningitis
neonatal pneumonia
neonatal sepsis
sepsis om pregnant
Cause endocarditis (inflammation of the heart), dental infections and abscesses?
Viridans group streptococci
What are the three staphylococci that can cause disease in humans?
aureus
epidermidis
saprophyticus
Staphylococcus aureus is coagulase ______
positive (can cause blood clot)
Gram positive cocci, chains
-catalase negative
-how they are classified:
=By their ability to hemolyze RBC’s in agar plate
=By antigenic characteristics of carbohydrate in cell wall (Lancefield antigens)
-Letters given for different Lancefield antigens (A, B, C, D, E, through S)
=5 are significant human pathogens. 3 are A, B, and D, while other two do not have Lancefield antigens
Streptococci
Gram-positive, catalase negative
-Group A streptococci
=Lancefield antigen “A”
=Carbohydrate found in cell wall
-Virulence factors
=M protein – inhibits complement activation and phagocytosis
=Antibodies against M protein aids in destroying organism
=Streptolysin O and Streptolysin S
=O is oxygen labile, S is oxygen stable
=Lysis red and white cells, responsible for beta hemolysis
-Diseases caused by include: Strep throat, scarlet fever, skin infections, Streptococcal toxic shock syndrome, rheumatic fever, post-streptococcal glomerulonephritis, and others
Streptococci pyogenes
Lancet-shaped gram positive cocci found in pairs (diplococci)
-No Lancefield type
-Major cause of bacterial pneumonia and meningitis in adults
-Otitis media(middle ear infection) in children
-Major virulence factor is its polysaccharide capsule
=Protects from phagocytosis
=Antibody against capsular polysaccharides are protective, Vaccines target these. Unfortunately, many serotypes of capsular antigens (antigenically different), thus vaccines target most common ones.
Streptococcus pneumoniae (also known as pneumococcus)
- Group B streptococci
- Neonatal meningitis, neonatal pneumonia, neonatal sepsis
- Sepsis in pregnant women
Streptococcus agalactiae
Cause endocarditis, dental infections, and abscesses
Viridans group streptococci
- Fever, myocarditis, migratory arthritis, rash, etc.
- Immune responses against M protein can cross react with heart tissue (molecular mimicry)
- Can cause permanent damage to heart valves
- Strep throat usually treated to prevent this complication, as most people will quickly recover from strep throat without treatment.
Rheumatic fever caused by antibody-mediated complications
- Occurs about 1 wk after pharyngeal or skin infections by nephritogenic strains of beta-hemolytic GAS.
- Ab-Ag complexes in circulation deposit in kidneys, result in damage due to complement and PMN.
- Generally, does not cause long term kidney damage
Acute post-streptococcal glomerulonephritis caused by antibody-mediated complications
Gram positive cocci, found in clusters like graps
Catalase positive
Staphylococci
-Coagulase positive (causes blood clot)
-Member of normal flora of nose and skin in many people problem in hospital
=Causes skin infections, pneumonia, osteomyelitis, endocarditis, etc
-Has proteins that disable defenses, tunnel through tissues, exotoxins
=Lots of virulence factors that contribute to it being a successful pathogen, Examples:
==Coagulase positive (distinguishes from other staphylococcal species)
==Fibrin formation around bacteria, preventing phagocytosis
==Hemolysins that destroy RBC’s, neutrophils and macrophages
==Protein A in cell wall – binds Fc portion of IgG antibody to prevent complement activation
==Toxins
**Enterotoxin – heat stable toxin that causes food poisoning (preformed toxin in food) E.g. potato salad and other food
**Toxic shock syndrome toxin (TSST-1) – superantigen that causes massive T cell activation with cytokine production, resulting in multiple symptoms including shock
Staphylococcus aureus
Multiple strains that can be found outside of the hospital. Tends to be sensitive to several oral antibiotics, e.g. clindamycin and trimethoprim-sulfamethoxazole
Community-acquired MRSA (CA-MRSA)
Multi-drug resistant, even against methicillin and Naficillin
- Vancomycin can be effective
- Vancomycin resistant strains (VRSA) are reported
Methicillin-resistant S. aureus (MRSA)
- Coagulase negative
- Normal flora of skin
- Nosocomial infections, including biofilms associated with prosthetic devices
- Resistant to antibiotics
Staphylococcus epidermidis
- Coagulase negative
- Urinary tract infections in sexually active women
Staphyloccus saprophyticus
Are aerobic (likes oxygen)
-Only bacteria with capsule composed of protein
=Prevents phagocytosis
-Anthrax – primarily affects herbivores, but can cause disease in humans
=Skin, gastrointestinal and pulmonary forms of disease
-Toxin composed of 3 proteins that are non toxic alone, but together produce the effects of anthrax
=Edema factor – impairs neutrophil function and causes edema
=Protective antigen – promotes entry of edema factor into cells
=Lethal factor – stimulates macrophages to release TNF and IL-1, contributing to death
-Rapid identification critical in treatment
Bacillus anthracis
Are anaerobic (cannot grow in oxygen)
-Pseudomembranous enterocolitis
-Gram (+) spore-forming rods
-Diarrhea following broad spectrum antibiotics
=Antibiotics wipe out normal flora, allowing pathogenic C. difficile to superinfect colon
-Toxins
=Toxins A and B damages mucosal cells so extensively that they no longer control water movement
=Toxin B is more cytotoxic than toxin A.
=Strains with new toxin: binary toxin CDT
-Treatment for C. difficile
=Metronidazole – mild disease
=Vancomycin – severe disease
=Spores resistant to antibiotics, and therefore relapse can occur (10-25%).
*Fidazomicin shown superior to vancomycin in treating recurrences
Clostridium difficile
Are anaerobic (cannot grow in oxygen)
-Lethal neurotoxin that causes a rapidly fatal food poisoning
-Exotoxin (neurotoxin) blocks the release of acetylcholine in nerve terminals, causing flaccid muscle paralysis.
-Spores found in smoked fish, home-canned vegetables
=If not cooked thoroughly, and then placed in anaerobic environment.
*Spores germinate, and bacteria grow and release toxin
Clostridium botulinum – botulism
Are anaerobic (cannot grow in oxygen)
- Spores commonly found in soil, enter skin through trauma
- Produces tetanus toxin, causing sustained contraction of skeletal muscles.
- “Lockjaw”
- Vaccine is against the toxin
Clostridium tetani – tetanus
Are anaerobic (cannot grow in oxygen)
- Spores found in soil, contaminates wounds
- Deep wounds with dead tissue, anaerobic environment.
- Bacteria grows and releases exotoxin enzymes
Clostridium perfringens – gaseous gangrene
Non-spore forming gram positive rods
- Causes diphtheria
- Pseudomembrane of fibrin, leukocytes, dead epithelial cells and bacteria in pharynx
- Exotoxin mediated
- Vaccine is against toxin
Corynebacterium diphtheriae
Non-spore forming gram positive rods
- Septicemia in pregnant women
- Neonatal meningitis and meningitis in immunosuppressed patients
Listeria monocytogenes
-Cause of leprosy, also called Hansen’s Disease
-WHO estimates about 2 million people infected with this organisms in the world
=Most in India, Brazil, Burma, Indonesia, Madagascar and Nepal
=In U.S., over 100 newly diagnosed cases per year.
• Usually in immigrants
-Impossible to grow this bacteria on artificial media
-Clinical manifestations are dependent upon 2 phenomenon:
=Severity dependent on host’s cell-mediated immune response
• Similar to that described for TB
=Bacteria appear to grow better in cooler body temperatures closer to skin surface
• Damages skin, superficial nerves, eyes, nose and testes
Mycobacterium leprae
o Smallest free-living organisms capable of self replication
o Lack cell wall (no peptidoglycan, etc)
o Cannot be gram-stained
o Only protective layer is a cell membrane
o Lipid bilayer packed with sterols (like cholesterol)
o Pleomorphic – many shapes but no defined shape
o Antibiotics against cell walls are ineffective, e.g. penicillin, cephalosporin
o Two major pathogenic species
=Mycoplasma pneumoniae
=Ureaplasma urealyticum
Mycoplasmatacea
o Number one cause of pneumonia in teenagers and young adults
More frequent in college dorms and military barracks
o Causes atypical pneumoniae (walking pneumonia)
Most often mild bronchitis and pneumonia, but there are cases of fatal pneumonia.
• Clinically these patients do not feel very sick
o Gradual onset of fever, sore throat, malaise and persistent dry hacking cough
After treatment, many symptoms disappear but the cough may last up to 2 months.
o Major virulence factor is P1 adhesion protein
Attaches to respiratory epithelium, causing ciliostasis and damage
o Diagnostic tests are available, but most times not used
Patients are treated with broad spectrum antibiotics that treat common causes of disease
• Another cause of atypical pneumonia is Chlamydia pneumoniae
Mycoplasma pneumoniae
o Also known as T-strain mycoplasma (T for tiny because of colony size on artificial media)
o Produces urease, which metabolizes urea into ammonia and CO2
o Part of normal flora of 60% if healthy women and commonly infects the lower urinary tract, causing urethritis
o Neisseria gonorrhoeae and Chlamydia trachomatis are the other 2 bacteria that cause urethritis
o Can cause pneumonia in neonates and play a role in infertility
Ureaplasma urealyticum
o Only pathogenic gram-negative cocci
o Found in pairs, e.g. diplococci
Each coccus shaped like kidney bean and the pair of cocci stick together with concave surfaces facing each other.
Neisseria
o Causes second most common sexually transmitted disease (STD)
o Urethral, rectal, eye, pharyngeal, joint (arthritis) infections
o In women, genital tract infections are clinically silent and can progress to pelvic inflammatory disease
Sterility, ectopic pregnancy, etc
o Urethral swabs will show gram-negative diplococcus within WBC
Neisseria gonorrhea (Gonococcus
o Pili
Attachment and prevent phagocytosis
Antigenic variation – Complex genes that undergo multiple recombinations, resulting in pili with hypervariable amino acid sequences
• Shift in antigenic type protects from existing antibodies
o Invasins - invasion into epithelial cells
Outer membrane protein porins (PorA, PorB)
Opa proteins (results in opaque colonies)
o Endotoxin (LPS) - promote inflammation.
o No capsule
N. gonorrhea: Virulence factors
o Pili (antigenic variation)
o LPS
• Has a capsule (gonococcus does not)
o Inhibits phagocytosis, unless antibody binds to it
o Different polysaccharides, at least 13 serogroups
caused by serogroups A, B, C
Vaccines are available
Neisseria meningitidis
o 5% population carry in nasal passages
o High risk groups for disease: Infants (6 mo to 2 yr), Army recruits and College freshmen
o Spread by respiratory route
o Diseases:
Rash consistent with invasive meningococcal infection
Endotoxin release is responsible, causing vascular necrosis, inflammatory reaction in skin
Meningitis (#1 cause) – common form of disease
• Often striking infants < 1 year of age
Bacteremia – severe cases could result in septic shock
o Diagnosis: Gram stain and culture of blood, spinal fluid or rash
o Treatment:
Patient: Penicillin G or Ceftriaxone
Close contacts: Rifampin or ciprofloxin
Meningococcal disease
carbohydrate portion of LPS
O antigen
capsule that covers O antigen
K antigen
subunit of flagella (if positive, motile bacteria)
H antigen
Enterobacteriacea
Vibrionacea
Pseudomonadaceae
Bacteroidaceae
Enterics
o Gram-negative rods o Many produce enterotoxins: all have endotoxin (LPS) o Transmission Fecal-oral Migration up the urethra Colonization of catheters in hospitalized patients o Many acquired antibiotic resistance o Pathogenic species Escherichia coli Klebseilla pneumonia Proteus mirabilis Shigella dysenteriae Salmonella typhi Yersinia enterocolitica
• Enterobacteriaceae
Heat labile toxin (LT) similar to cholera toxin
Heat stable toxin (ST)
o Enterotoxigenic E. coli (ETEC)
Shiga-like toxin (verotoxin) – similar action to Shigella toxin
Attach with pili and toxin leads to intestinal epithelial cell death
Bloody (hemorrhagic) diarrhea
E. coli strain O157:H7 is part of this group
o Enterohemorrhagic E. coli (EHEC)
Invades into epithelial cells, like Shigella
Bloody diarrhea
o Enteroinvasive E. coli (EIEC)
o Pneumonia (commonly in alcoholics or those with underlying lung disease) o Hospital acquired urinary tract infections and sepsis
• Klebsiella pneumoniae
o Dysentery – BLOODY diarrhea
o Shiga toxin – kills intestinal epithelial cells
• Shigella dysenteriae
o Fecal-oral transmission
o Carrier state – “Typhoid Mary”
o Invades cells, including epithelial cells and macrophages
o Can survive intracellularly in macrophages/monocytes
o Spread to lymph nodes and finally other organs
• Salmonella typhi
Cholera
o Vibrio cholera
Diarrhea due to eating raw seafood
o Vibrio parahaemolyticus
Bloody diarrhea due to zoonotic infection
o Campylobacter jejuni
Peptic ulcers
o Helicobacter pylori
Anaerobic gut bacteria causing infections due to surgical or trauma damage to intestines
o Bacteroides fragilis
• Hospital-acquired gram-negatives
o Often arise from endotracheal tubes, foley catheters, i.v. catheters and surgical incisions.
o Most common group is the Enterobacteriacae family of gram-negative bacteria
E. coli, Klebsiella and Enterobacter
o Healthy people are typically resistant to disease due to this organism
o Can cause:
Pneumonia, e.g. cystic fibrosis and cancer patients
Osteomyelitis, e.g. diabetic patients, i.v. drug users
Burn-wound infections
Sepsis (high mortality rate)
UTI and pyelonephritis
Endocarditis (common cause of endocarditis, along with S. aureus, with i.v. drug users)
• Pseudomonas aeruginosa
o Can survive on environmental surfaces, increasing chances of transmission
o Pneumonia, bacteremia, UTI, burn/wound infections and eye infections
Very common infection in soldiers with wounds
o Can be mistaken for Neisseria
Coccobacillus and on solid media can form diplococci
Sometimes could look gram-positive as well
o Challenge to treat due to multidrug resistance
• Acinetobacter baumannii
o Small gram-negative rod (coccobacillus)
Cause of sinusitis, otitis media, meningitis, pneumonia mostly in children
o Polysaccharide capsule – multiple serotypes
Type b serotype more invasive than others
Anti-capsule antibody confers protection
• Maternal antibodies protect baby for first 6 months
• Between 6 months to 3-5 years old children are lacking these antibodies (Type b most important)
• Vaccine is available
• Haemophilus influenza
o Meningitis
Main cause of meningitis in children (6 months to 3 yrs) until vaccine was introduced
Potentially fatal infection or development of neurologic deficits.
Following inhalation the organism reaches blood stream allowing penetration into brain
o Acute epiglottitis
o Septic arthritis
o Sepsis
• H. influenzae type b Diseases
o Usually limited to upper airways
o Increased lymphocytes often seen in these patients
o Exotoxins
Pertussis toxin (AB toxin) – activates adenylate cyclase (precise role unknown)
Extracytoplasmic adenylate cyclase – impairs the function of inflammatory cells
Tracheal cytotoxin – destroys ciliated epithelial cells. May be responsible for violent (whooping) cough
• Bordetella pertussis – Whooping cough
o Cause of Pontiac fever and Legionaires’ disease
o Aerosolized contaminated water is inhaled
Form biofilms in water towers, air conditioning systems, whirlpools, etc.
o Intracellular pathogen
Lives in amoebas in water
Lives inside macrophages by inhibiting phagosome-lysosome fusion
• Legionella pneumophila
o Can only survive by establishing residence inside animal cells
o Need host’s ATP as an energy source
Obligate intracellular bacteria
o Chlamydia
C. trachomatis – Eye infections, non-gonococcal urethritis, etc
C. pneumoniae – Atypical pneumonia
o Rickettsia
Tend to be zoonotic or vector borne, e.g. from animals or insects
Example: R. rickettsia – Rocky mountain spotted fever (Tick borne)
o Tiny gram-negative bacteria that look like corkscrews
Motile with axial filaments winding around organism
• Contraction causes spinning motion
• Spirochetes
Primary stage – Painless chancre (ulcer)
Secondary stage – Rash on palms and soles, painless wart like lesion, almost any organ can be infected
Tertiary stage – can develop over 6-40 years
• Slow inflammatory damage to organ tissue, small blood vessels or nerve cells
Latent – secondary syphilis has resolved but relapses can occur
Congenital – Acquired in utero with high mortality rate
o Treponema pallidum – syphilis (STD)
Lyme disease (tick-borne) • Rash, neurologic infections, cardiac infection, arthritis
Borrelia burgdorferi
