Bacterial Pathogenesis Flashcards
Normal microbiota
o Organisms that proliferate harmlessly in a particular site in healthy individuals
• 10% are microbial
o Composition depends on age, gender, stress, diet, disease states, and drug effects
Define and discuss the terms commensal, mutualistic, opportunist, and pathogen
Commensal
o Microorganism deriving benefits from a host that neither suffers nor gains benefit from relationship
o Long have considered this to be normal microbiota
Mutualistic
o Benefits for both
o More recently: relationship between microbiota and human host
Opportunist
o Infections occurring when host defenses are weakened to such an extent that organisms not normally causing infection now are able to
o Ex.
• Bowel microbiota: causing peritonitis and sepsis after breach of bowl wall (escapes normal niche)
• Oropharyngeal microbiota: causing pneumonia after aspiration into lungs (escapes normal niche)
• Toxigenic Clostridium difficile: causing pseudomembranous colitis after antibacterial antibiotic treatment disrupts bowl microbiota (allowing opportunistic outgrowth)
• Candida albicans: causing vulvovaginal candidiasis after antibacterial antibiotic treatment disrupts vaginal microbiota (allowing opportunistic outgrowth)
Pathogen
o Organism causing damage and disease (symptoms/signs of illness) via interaction with host
o May be endogenous (part of normal microbiota) or exogenous
Describe the carrier state
o Person harboring a pathogen but not exhibiting clinical disease
o Possible source of infection to others
o May be transient or persistent
Ex.
• Streptococcus pneumoniae: may colonize nasopharynx of asymptomatic carrier followed by aerosol transmission to another person who gets pneumococcal URI (AOM or sinusitis) or pneumonia
• Salmonella typhi: may establish a reservoir site in gallbladder of asymptomatic carrier, followed by fecal shedding and fecal-oral transmission to another person who contracts typhoid fever
Discuss the benefits derived from normal microbiota as well as the disadvantages
Benefits:
o Host defense against pathogens
• Physical/chemical barriers, filling niches
• Competition for nutrients
• Production of antimicrobial factors (fatty acids, bacteriocins)
• Environmental modulation (acid pH, oxidative compounds)
o Vitamin synthesis (K, B vitamins)
Disadvantages:
o Becoming an “occasional pathogen” (normal microbiota in absence of symptoms/signs of disease, but can be responsible for disease)
o Become pathogenic by escaping normal niche
o Become pathogenic via opportunistic outgrowth after disruption by antibiotics, environmental changes, etc.
Describe the innate properties of the body and how non-specific immunity defends against infection
Innate immunity
o Normal microbiota (competes for niches; keeps immune system stimulated)
o Epithelial barriers, skin, mucous membranes
o Mucus, mucosal secretions, lysozyme, defensins, fatty acids, acidic pH
• Lysozyme: enzyme in tears, saliva, and nasal secretions; hydrolyzes Gram-positive cell wall
• Secretory IgA: in mucus layers and glandular secretions like breast milk; prevents attachment of organisms to epithelium
o In → outward movement (upper respiratory mucociliary excalator, urine flow, gut peristalsis)
o Phagocytes (macrophages, neutrophils) NK cells
o Complement
o Iron sequestration, nutritional immunity
o Elevated temperature (37°C or higher)
Specific immunity
o Cell mediated
o Antibody mediated
Discuss how bacteria gain entry into the body and attach to target cells.
Entry o Ingestion o Inhalation o Trauma o Needle stick, indwelling catheters o Arthropod bite o Sexual transmission
Attachment (to avoid being swept away by peristalsis or mucus escalator or flushing action)
o Adhesions bind to specific receptors on host cell surface
Ex.
• Staphylococcus areus uses lipoteichoic acid
• E. coli use pili
Discuss the role of virulence factors.
- Virulence factors = phenotypic traits allowing microbe to enter, survive, grow and cause damage in host
- May be encoded on chromosome, plasmids, or phage
Include: o Adhesions o Biofilm formation o Quorum sensing o Toxins o Degradative enzymes o Superantigens o Induction of excess inflammation o Evasion of phagocytic and immune clearance o Capsule production o Resistance to antibiotics o Intracellular growth
Describe the effects (both local and distant) of bacteria on host cells
Local effects
o Enzymes that break down cells and ECM of host tissues (then able to quickly spread through host CT)
• Hyaluronidase: streptococci, staphylococci, clostridia
• Collagenase: some clostridia
o Enzymes that attack cell membranes → lysis
• Hemolysins: lyse RBCs
• Coagulase: enzyme from staphylococcus aureus; converts fibrinogen → fibrin = clot (difficult for phagocytes and/or antibiotics to reach bacteria)
Distant effects
o Endotoxins: microbial cell associated
• Ex. Lipopolysaccharide (LPS) of Gram-negative microbes
• Due to core lipid A portion = activates complement and stimulates IL-1 and TNF production
• Result: fever, shock, possible death
o Exotoxins: proteins secreted by Gram-negative and –positive microbes
• Different mechanism: can lyse cells, interfere with neural transmission, affect lining of GI tract
• Superantigens (of streptococcus pyogens and staphylococcus aureus) nonspecifically bind T cell receptors → massive cytokine release → toxic shock syndrome
Explain why biofilms form and their role in disease
- Mats of immobile organisms stuck to a solid surface
- Use quorum sensing = turn on biofilm formation genes and modulate expression of other virulence factors
- When bacteria aggregate = communicate with neighboring microbes via autoinducers (signaling molecules) → able to measure population density
- Make LOTS of extracellular polysaccharides → impermeable 3D structure
- Immune system has trouble reaching bacteria in biofilm
- Often need to remove colonized catheter or prosthetic joint
Discuss how bacteria are able to evade the immune system.
Polysaccharide capsules o Prevent attachment or protect against complement-mediated lysis IgA protease secretion Antigenic variation o Genetic recombination so expressed surface antigen can assume many different antigenic structures (ex. Gonococcus has many different genes for pili) Inhibition of chemotaxis Inhibition of phagocytosis Inhibition of phagolysosome fusion Resistance to lysosomal enzymes Intracellular replication
Discuss how transmission occurs between hosts.
Vertical
o Mother → child
o Transplacental or perinatal (during birth)
Horizantal (person to person)
o Close contact
o Vectors (via animate transmission vehicle, commonly an arthropod)
o Fomites (inanimate transmission vehicle)
List the 8 antibiotics or antibiotic classes
- Penicillins
- Cephalosporins
- Vancomycin
- Tetracyclines
- Aminoglycosides
- Macrolides
- Fluoroquinolones
- Trimethoprim-sulfamethoxazole (TMP-sulfa)
Penicillins
o β-lactam antibiotics (named after structure)
o Interfere with synthesis of bacterial petidoglycan cell wall
o Ex.
• Pen G
• Dicloxacillin
• Ampicillin
• Pipercillin
Cephalosporins
o β-lactam antibiotics o Cell wall synthesis inhibitor (but more resistant to inactivation by β-lactamases) o Examples • 1st generation: Cephalexin • 2nd: Cefoxitin • 3rd: Ceftriaxone • 4th: Cefepime • 5th: Ceftaroline
Vancomycin
o Inhibits cell wall synthesis
o Useful for β-lactam allergic persons
o Should be reserved for serious β-lactam resistant infections
