Bacteria

Aka: Bacteria, Bacterial Infection, Bacterial Function, Bacterial Toxin, Endotoxin, Enterotoxin, Bacterial Exotoxin, Encapsulated Bacteria, Microbial Biofilm, Bacterial Genetics, Transposon, Plasmid, F-Plasmid, Bacteriophage, A-B Toxin

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II. Pathophysiology: Bacterial Structure

  1. Bacterial cell wall is multi-layered
    1. Outer cell membrane (only present in Gram Negative Bacteria)
    2. Peptidoglycan layer
      1. Thicker layer in Gram Positive Bacteria (allows for blue, crystal violet stain uptake)
      2. Thin and more simple layer in Gram Negative Bacteria
    3. Inner cytoplasmic membrane
      1. Phospholipid bilayer with embedded Proteins
  2. Bacterial Shapes
    1. Cocci
    2. Bacilli (rods)
    3. Spiral, comma or S-Shaped
    4. Pleomorphic (no distinct shape)
  3. Grouping
    1. Pairs (dipolococci)
    2. Chains (e.g. Streptococcus)
    3. Clusters (e.g. Staphylococcus)
  4. Flagella
    1. Long Protein filaments extending from Bacterial cells
    2. Flagella allow for Bacterial motility, typically toward or away from concentrated chemicals (chemotaxis)
    3. Basal bodies attach flagella to Bacterial cell walls
      1. Basal bodies extend through the entire Bacterial cell wall, bound to cell membranes
      2. Basal body spins freely in the cell membranes and in turn rotates the attached flagellum
    4. Types
      1. Single Polar flagellum or Monotrichous (e.g. Vibrio Cholera)
      2. Many, circumferential peritrichous flagella (e.g. Escherichia. coli, Proteus mirabilus)
      3. Periplasmic flagella (course beneath the outer membrane of Spirochetes)
      4. Dual amphitrichous flagella on opposite sides of the Bacterial cell (e.g. Campylobacter jejuni)
      5. Lophotrichous flagella with multiple flagella eminating from a single part of Bacterial cells (e.g. Helicobacter Pylori)
  5. Fimbraiae (Pili)
    1. Bacteria covered in hair-like fashion, with short filaments, composed of repeated pilin Protein, and eminating from the cell wall
    2. Pili functions
      1. Adherence (Adhesins)
        1. Neisseria gonorrhoeae (pili adhere to cervical, Urethral and buccal cells)
        2. Escherichia coli (Bladder or intestinal epithelium)
        3. Bordetella Pertussis (ciliated respiratory epithelium)
      2. Defense (e.g. against Phagocytosis)
      3. Genetic Material exchange (F Pili)
  6. Encapsulated organisms (Polyosides)
    1. Some Bacteria secrete protective coatings or capsules, composed of sugar residues (Polysaccharides), over the outer cell wall
      1. Streptococcus Pneumoniae
      2. Haemophilus Influenzae
      3. Salmonella typhi
      4. Klebsiella
      5. Bacillus anthracis (uniquely composed capsule of Amino Acids)
      6. Neisseria Meningitidis
      7. Pseudomonas Aeruginosa
    2. Capsules prevent Phagocytosis of Bacterial organisms by immune cells (e.g. Macrophages)
    3. Detection
      1. Colonies of encapsulated organisms are known as "smooth" due to their appearance on culture media
      2. Some stains have been developed to identify specific encapsulated organisms
    4. Protection
      1. Spleen is key to filtering encapsulated organisms (and Asplenic patients are at high risk for overwhelming infections)
      2. Some Immunizations are directed against capsule sugar residues (e.g. Pneumococcal Vaccine)
  7. Biofilms
    1. Polysaccharide scaffolding secreted by Bacteria on their surface
    2. Biofilms allow for Bacterial adherence to tubes and catheters
    3. Biofilms protect Bacteria from immune cells and Antibiotics
  8. Endospores
    1. Endospores are dormant Bacterial spores, highly resistant to antiseptic measures (chemicals, heat, boiling)
      1. Two outer layers of exosporium surrounding a keratin-like Protein layer
      2. Three inner layers of a peptidoglycan layer sandwiched between two cell membranes
    2. Endospores are dormant forms of Bacilus and Clostridium Bacteria
      1. May be activated after many years dormant (e.g. in soil) under favorable growth conditions
      2. On activation, they become human pathogens (e.g. Tetanus, Anthrax)
    3. Effective disinfection methods to destroy endospores
      1. Autoclave (115 C) for 15 minutes
      2. Burning

III. Pathophysiology: Bacterial Genetics

  1. DNA, RNA and Proteins
    1. Double stranded DNA
      1. A single loop of double stranded DNA is the typical genetic makeup of Bacteria
      2. Bacterial DNA is haploid (single copy per cell) and is NOT encased in a nuclear membrane
      3. Bacteria may also acquire small DNA loops (Plasmids) from other Bacteria, conferring resistance
    2. Ribosomes
      1. As in higher organisms, ribosomes translate RNA to Protein synthesis
      2. Bacterial ribosomes are 70S, smaller than multi-cellular organisms (80S)
      3. Bacterial ribosomes have 2 subunits
        1. Subunit 50S (targeted by Erythromycin)
        2. Subunit 30S (targeted by Tetracycline)
  2. Exchange of genetic material
    1. General
      1. When Bacterial cells reproduce, they pass along an exact copy or clone of their DNA
      2. Bacterial cells rely on 4 key mechanisms to introduce genetic variability beyond point mutations
    2. Transformation
      1. Lysed Bacteria will release free floating DNA which can be taken up by competent receiving cells
      2. Competent receiving Bacterial cells are able to bring intracellularly free DNA from related Bacteria
      3. Once intracellular, the free DNA is incorporated into the recipient if similar to the hosts DNA
    3. Transduction
      1. Bacteriophages (Phages)
        1. Bacteriophages are viruses which infect Bacterial cells
        2. Bacteriophages contain either DNA or RNA encased within a Protein coat (capsid)
        3. Phages bind Bacterial cell surfaces (via fibrous tails) and transfer DNA into target Bacteria
          1. Phages coopt Bacterial RNA Polymerase to transcribe phage DNA into mRNA
          2. Resulting mRNA translates into Proteins and enzymes that generate new phages
          3. Bacterial cells swell with new phages, which are released when the cells lyse
        4. Phages are of 2 types
          1. Virulent phages have more immediate effects on phage production and Bacterial cell lysis
          2. Temperate phages incorporate their DNA (prophage) into Bacterial DNA
            1. Resulting lysogenic Bacteria are initially unaffected, as the prophage DNA is inactive
            2. Prophage produces repressor Proteins preventing another phage from infecting same cell
            3. Later, once activated
              1. Prophage DNA is spliced out of Bacterial DNA to be encased in new phages
              2. Prophage DNA is transcribed with new phages formed and cell lysis
      2. Generalized Transduction (Virulent phage mediated)
        1. Newly formed phages may accidentally encase Bacterial DNA instead of phage DNA
        2. When resulting phage infects a new Bacterial cell, it will transmit Bacterial DNA
        3. Since the infecting phage does not contain phage DNA, the Bacterial cell is unharmed
        4. Target Bacterial cell may incorporate the new DNA (as in Transformation)
          1. Acquired DNA may code for new functionality (e.g. Antibiotic Resistance)
      3. Specialized Transduction (Temperate phage mediated)
        1. Temperate phages, when activated, splice prophage DNA out of Bacterial DNA
        2. If splicing error occurs, Bacterial DNA may also be spliced out with prophage DNA
          1. In this way, Bacterial DNA may be included in newly generated phages
          2. When phages infect new Bacterial cells, they may transmit Bacterial DNA
    4. Conjunction
      1. Self Transmissible Plasmid (F-Plasmid or Fertility Plasmid)
        1. Circular dsDNA separate from a Bacteria's main Chromosome
        2. Plasmids are polygenic, coding for various functionality (e.g. Antibiotic Resistance)
        3. Plasmids also encode their own transmission mechanism (formation of a sex pilus)
      2. Conjunction Mechanism
        1. DNA is passed via adjacent Bacterial cells from cells with F-Plasmids (F+ cells)
        2. F+ cells form a long Protein tube (sex pilus) that penetrates an adjacent Bacterial cell
        3. F-Plasmid dsDNA (double stranded) is divided into 2 ssDNA (single stranded) by a nuclease
          1. One ssDNA enters the adacent cell, and then pairs with Nucleotides to form dsDNA
          2. Source F-Plasmid pairs with Nucleotides to again form dsDNA
        4. Recipient Bacterial cell, now contains an F-Plasmid and is F+
        5. Uncommonly, Plasmid DNA may be incorporated into Bacterial DNA (Hfr Cell)
          1. Future transmission to an F- cell may transmit DNA from both Chromosome and Plasmid
          2. F-Prime-Plasmid (F'-Plasmid) may also be formed (similar to specialized transduction)
            1. F'-Plasmid is formed when some Bacterial DNA is excised with Plasmid DNA
    5. Transposons
      1. DNA Transposable Elements that can excise and reintegrate into another genome site
      2. Transposons may insert into the DNA of phages, Plasmids and Bacterial Chromosomes
      3. Transposons often contain incomplete, nonfunctional genes or may inactivate other genes when they insert
        1. However, Transposons may also contain full genes that encode new functionality (e.g. Antibiotic Resistance)

IV. Pathophysiology: Bacterial Function

  1. Oxygen Toxicity Counter Mechanisms and Oxygen Utilization
    1. Oxygen is toxic to Bacteria (forming Hydrogen Peroxide and other radicals) without counter mechanisms
      1. Both catalase and peroxidase break down hydorgen peroxide
      2. Superoxide dismutase breaks down superoxide radicals
    2. Oxygen utilization
      1. Obligate aerobes
        1. Require oxygen for TCA Cycle (Kreb Cycle) or energy synthesis
        2. Have all 3 enzymes to prevent against Oxygen Toxicity (catalase, peroxidase, superoxide dismutase)
      2. Facultative Anaerobes
        1. Aerobic Bacteria that can survive in anaerobic environments (but prefer aerobic conditions)
        2. Have 2 enzymes to prevent against Oxygen Toxicity (catalase, superoxide dismutase)
        3. Energy production is by either TCA Cycle or by fermentation (Glycolysis)
      3. Microaerophilic Bacteria (aerotolerant Anaerobes)
        1. Anaerobic Bacteria that can survive in aerobic environments (but prefer anaerobic conditions)
        2. Have superoxide dismutase to prevent against Oxygen Toxicity
        3. Energy production is by fermentation (Glycolysis), not by TCA Cycle (so no benefit to oxygen)
      4. Obligate Anaerobic Bacteria
        1. Obligate Anaerobes cannot survive in oxygenated environments
        2. No enzymes to protect against Oxygen Toxicity
        3. Energy production is by fermentation (Glycolysis), not by TCA Cycle (so no benefit to oxygen)
      5. Obligate Intracellular Bacteria
        1. These Bacteria (e.g. Chlamydia, Rickettsia) do not have the mechanisms to produce their own energy
        2. Rely on host cells to produce ATP, which then crosses the Intracellular Bacterial cell membranes
  2. Energy Utilization
    1. Light utilization (phototrophs)
    2. Chemical utilization (chemotrophs)
      1. Inorganic chemical use such as ammonium (autotrophs)
      2. Ogranic chemical use such as Glucose (heterotrophs, includes most human pathogens)
    3. Glucose utilization (Glycolysis)
      1. Anaerobic conditions (fermentation)
        1. Glucose is broken down via Glycolysis and then pyruvate is converted to one of many acids (e.g. Lactic Acid)
      2. Aerobic conditions (cellular respiration)
        1. Glucose is broken down via Glycolysis and then pyruvate enters the TCA Cycle (Kreb Cycle)

V. Pathophysiology: Toxins and Inflammatory Mediators

  1. Immune Cell Released Mediators in Sepsis (endogenous host response)
    1. Tumor Necrosis Factor (TNF, Cachectin)
      1. Macrophage and Neutrophil released highly inflammatory factor
      2. Triggers inflammatory cascade including Interleukin-1 release
    2. Interleukin-1
      1. Cytokine released from Macrophages and endothelium
      2. Triggers release of various other inflammatory mediators
  2. Bacterial Endotoxins (Gram Negative Bacterial cell wall toxin)
    1. Lipid A, a highly potent toxin, and part of the Gram Negative Bacterial outer membrane
    2. Lipid A is released at low steady levels by live Bacteria, and in large release on Bacterial cell destruction
  3. Bacterial Exotoxins (Bacterial secreted toxins)
    1. Neurotoxins
      1. Toxins active a nerves and neuromuscular endplates
      2. Examples: Botulinum Toxin, Tetanus toxin
    2. Tissue Invasive Exotoxin (invasive Bacterial Infection with tissue destruction)
      1. Streptococcus Pyogenes (e.g. hemolysin O and S, Streptokinase, hyaluronidase, DNAase, NADase)
      2. Staphylococcus Aureus (e.g. staphylokinase, Penicillinase, Lipase, exfollatin, leukocidin)
      3. Clostridium perfringens (many toxins, including Alpha/lecithinase)
    3. Pyrogenic Exotoxin (erythrogenic toxins)
      1. Superantigens (esp. with Streptococcus) trigger inflammatory Cytokine release from T Cells
      2. Associated with Toxic Shock Syndrome, Scarlet Fever
    4. Enterotoxins
      1. Preformed Toxins (Food Poisoning)
      2. Bacterial colonization (Infectious Diarrhea)
    5. A-B Toxins
      1. Two toxin polypeptide subunits bound together by disulfide bonds
        1. B-Binding (or H-HoldingOn) Subunit
        2. A-Action (or L-Laser) Subunit
      2. Mechanism
        1. B-Subunit binds specific host Target Cell receptors
        2. A-Subunit enters Target Cells and initiates anti-host cell activity

VI. Types: Gram Positive Bacteria

  1. Cocci
    1. Facultative Anaerobes
      1. Staphylococcus (cocci in clusters)
    2. Microaerophilic
      1. Streptococcus (cocci in chains, except Pneumococcus which is in pairs)
      2. Enterococcus (cocci in chains)
  2. Rods
    1. Obligate Anaerobes
      1. Clostridium (spore forming)
    2. Facultative Anaerobes
      1. Corynebacterium
      2. Listeria
      3. Bacillus anthracis (spore forming)
    3. Obligate aerobes
      1. Bacillus Cereus (spore forming)
      2. Mycobacterium (weakly Gram Positive but strongly acid-fast)
  3. Branching
    1. Facultative Anaerobes
      1. Actinomyces
    2. Obligate aerobes
      1. Nocardia (also weakly acid fast)

VII. Types: Gram Negative Bacteria

  1. Cocci
    1. Obligate aerobes (all are cocci in pairs)
      1. Neisseria
      2. Moraxella catarrhalis
      3. Haemophilus Influenzae (also considered pleiomorphic or coccobacillus)
  2. Rods (in general)
    1. Facultative Anaerobes
      1. Francisella
      2. Pasteurella
      3. Gardnerella
    2. Obligate aerobes
      1. Bordatella
      2. Legionella
      3. Brucella
  3. Rods (gastrointestinal or Enteric Bacteria)
    1. Obligate Anaerobes
      1. Bacteroides
    2. Facultative Anaerobes
      1. Escherichia coli (has flagella)
      2. Shigella
      3. Salmonella
      4. Yersinia
      5. Klebsiella
      6. Proteus
      7. Enterobacter
      8. Serratia
      9. Vibrio (has flagella)
      10. Helicobacter
    3. Microaerophilic
      1. Campylobacter
    4. Obligate aerobes
      1. Pseudomonas
  4. Spirochetes (spiral-shaped, in thin tight coils and periplasmic flagella)
    1. Although Gram Negative, too small to see on standard light microscopy
      1. Require Dark-field Microscopy
      2. Also immunologically silent with an extra outer membrane with few protein Antigens (cloaks the organism)
    2. Microaerophilic
      1. Treponema
      2. Borrelia
      3. Leptospira
  5. Pleomorphs
    1. Obligate aerobes
      1. Bartonella (facultative intracellular)
    2. Obligate Anaerobes (also obligate intracellular)
      1. Chlamydia
      2. Rickettsiae

VIII. Types: Miscellaneous Bacteria

  1. Gram Neutral Coccus (no cell wall)
    1. Facultative Anaerobe
      1. Mycoplasma
  2. Facultative Intracellular Organisms
    1. Bacteria that survive and propogate within Phagocytes (e.g. Neutrophils, Macrophages)
    2. These Bacteria survive by suppressing Lysosome-induced destruction within Phagocytes
    3. Examples
      1. Bartonella Henselae
      2. Brucella
      3. Francisella Tularensis
      4. Legionella
      5. Listeria monocytogenes
      6. Mycobacterium
      7. Nocardia
      8. Salmonella typhi
      9. Yersinia
  3. Acid Fast Bacteria and weakly Gram Positive (Mycobacterium)
    1. Mycobacterium tuberculosis
    2. Mycobacterium marinum
    3. Mycobacterium Avium Complex
    4. Mycobacterium bovis
    5. Mycobacterium scrofulaceum
    6. Mycobacterium ulcerans
    7. Mycobacterium leprae (Leprosy, Hansen's Bacillus)

IX. Complications

  1. Bacteremia
  2. Sepsis
  3. Septic Shock (endotoxic shock)
  4. Toxic Shock Syndrome

X. References

  1. Davis (1990) Microbiology, Lippincott, p. 21-50
  2. Gladwin (2014) Clinical Microbiology, Medmaster, Miami, p. 1 to 26

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