Bacteria, Toxins, & Virulence Flashcards
Koch’s Postulates
- Specific microbe is present regularly in characteristic lesions of the disease
- This microbe can be isolated and grown in vitro
- Injection of the cultured microbe into animals reproduces the disease in animals
- The specific microbe can be re-isolated from lesions of the disease in animals
Pathogen
A microbe capable of causing host or damage; includes classical and opportunistic pathogens; damage can result from direct microbial action or host immune response
Pathogenicity
The capacity of a microbe to damage a host
Virulence
Relative capacity of a microbe to damage a host
Compared by ID50 (minimally infective dose in 50%), DD50 (disease producing dose in 50%), and LD50 (lethal dose in 50%)
Peptidoglycan
Forms a rigid mesh surrounding the cytoplasmic membrane of bacteria
Basic subunit consists of two alternating sugars (GlcNAc and MurNAc) and a 5 amino acid tail hanging off of MurNAc terminating in D-ala-D-ala
Transglycosylation joins the MurNAc and GlcNAc residues of adjacent subunits
Transpeptidation cleaves the terminal D-ala and joins the amino acid tails, allowing cross-linking
Lysozyme
Enzyme present in many body secretions; contributes to innate host defenses against bacteria by hydrolyzing peptidoglycan at the glycosidic bond between MurNAc and GlcNAc
Gram Negative
Has an outer membrane containing LPS, lipoproteins, and porins; LPS is located exclusively in the outer leaflet of the OM and phospholipids are located in the inner leaflet
Gram Positive
Contains a single cytoplasmic membrane; cell wall contains greater degree of peptidoglycan cross-linking; cell wall also contains Teichoic acids, which form a repeating polyglycerol-P or polyribitol-P backbone; lipoteichoic acids help anchor the cell wall to the membrane
Lipopolysaccharide (LPS)
Contains lipid A, the toxic component of endotixin, a core polysaccharide, and an oligosaccharide that functions as an antigen (O antigen)
Bacterial ribosomes
30S + 50S = 70S
DNA is located in the cytoplasm so transcription and translation are coupled; polyribosomes transcribe on one mRNA molecule simultaneously and mRNA may be “polycistronic,” coding for multiple proteins
Bacterial cytoplasmic membrane
AKA “inner membrane” in gram-negative bacteria; lipid bilayer made up of phospholipids and proteins but no sterols; exhibits selective permeability, essentially impermeable to all charged substances including protons; only hydrophobic molecules smaller than glycerol can diffuse
Phases of the Bacterial growth curve
- Lag phase - physiological adjustment to new medium
- Exponential (logarithmic) phase of growth - rate of increase in cell mass is proportional to the cell mass already present; a constant interval of time is required for doubling cell mass (generation time)
- Stationary phase - growth plateaus as essential nutrients are consumed and toxic metabolites accumulate
- The number of viable bacteria decreases as autolysis occurs
Heterotrophic Bacteria
Bacteria that require an organic carbon source, includes most bacterial pathogens
Autotrophic Bacteria
Bacteria that obtain their carbon exclusively from CO2
Fastidious Bacteria
Bacteria that are deficient in one or more biosynthetic pathways and require, in addition to sources of carbon and energy, a number of essential growth factors (AAs, purines/pyrimidines, and inorganic ions)
Obligate Intracellular Bacteria
Bacteria that can only live within eukaryotic cells
Strict Aerobe
Requires oxygen, cannot ferment
Ex: Mycobacterium tuberculosis
Strict Anaerobe
Killed by oxygen; fermentative metabolism
Ex: Clostridium
Indifferent (Aerotolerant anaerobe)
Ferments in presence or absence of O2
Ex: Strptococcus pyogenes
Facultative
Respires with O2, ferments in absence of O2
Ex: E. coli, Staph aureus
Microaerophilic
Grows best at low O2 but can also grow without O2
Fermentation
Organic compounds serve as both electron donors and electron acceptors; no net oxidation of substrates occurs; undertaken by:
Strict anaerobes
Facultative & indifferent bacteria - grown under anaerobic conditions
Indifferent organisms (aerotolerant anaerobes)
Ex: Glucose –> Ethanol
Bacterial respiration
Carbon compounds are oxidized by passage through the respiratory chain located in the cytoplasmic membrane; molecular oxygen (aerobic) or inorganic substrates (anaerobic) are final electron acceptor
Glucose –> CO2
Sporulation
A response to adverse nutritional conditions; spores are highly resistant, dehydrated, and have no metabolic activity; they can survive for long periods of time under adverse conditions and germinate when conditions improve to convert back to vegetative cells
Gram positive cocci
Streptococci (pneumoniae, pyogenes)
Staphylococci (aureus - MSSA, MRSA)
Enterococci (faecium)
Gram negative cocci
Neisseria (meningitidis, gonorrheae)
Atypical bacterial pathogens
Chlamydia, Mycoplasma
Gram positive rods - anaerobic
Clostridium (difficile, tetani, botulinum)
H. pylori
Gram negative rod - anaerobic
Bacteroides fragilis
Toxin Class - Spreading factors
Toxic enzymes secreted by microbial pathogens that break down the ECM, allowing the microbe to spread through tissues and cause disseminated infection
Ex: Collagenase, elastase, hyaluronidase
Toxin Class - Cytotoxins
Generally, toxins that act on the plasma membrane to cause cellular damage
Often toxins that insert into membranes and assemble into multimeric complexes that form pores, causing lysis of target cells
Ex: a-Hemolysin of Staph aureus
Toxin Class - Superantigens
Potent T-cell activators; bi-functional molecules that bind simultaneously to conserved region of MHC-II on antigen presenting cells AND to a conserved region of the TCR, generating a cytokine response that is independent of specific antigenic effects
Ex: Toxic Shock Syndrome Toxin (TSST-1) of Staph. aureus
Pyrogenic exotoxins of Strep. pyogenes
Cholera Toxin
Toxin Class: Intracellular signal disruption; produced by Vibrio Cholerae
B subunit binds the GM-1 receptor initiating endocytosis of the A subunit; in the cytosol, subunit A ADP-ribosylates the alpha subunit of the Gs protein, leading to its constitutive activation; Gs activates Adenylate Cyclase, which increases production of cAMP; cAMP binds the CFTR channel causing efflux of Cl- and water into the gut
Pertussis Toxin
Toxin Class: Intracellular signal disruption
ADP-ribosylates and inactivates the alpha subunit of inhibitory Gi protein; decreased inactivation of Gi leads to increased activity of Adenylate Cyclase and increased production of cAMP