General pathology of bacterial infections

GENERAL PATHOLOGY OF BACTERIAL INFECTION

  • Bacteria may be extracellular or intracellular (Mycobacterium, Brucella)
  • Contain both RNA and DNA
  • Lack nucleus
  • Lack few cytoplasmic organelles
  • Reproduce by binary fission

Classification of bacteria

Based on morphological, cultural, biochemical, antigenic and nucleic acid parameters 

Morphological appearance

  • Round (micrococci) ; Chains of cocci (streptococci); Rods (bacilli); Filamentous with branching (Actinomyces)
  • Some bacteria have cilia and flagella
  • Staining characteristics– Based on Gram's staining classified as Gram’s positive & Gram’s negative
  • Virulence or pathogenecity – Staphylococci & Streptococci live in the nasopharynx & skin of normal animals and cause disease through wounds or immunosuppressed animals; Other streptococci are not normal inhabitants and produce disease
  • Some bacteria are highly invasive multiply and spread rapidly producing bacteraemia and septicaemia like Bacillus anthracis
  • Localised infection develops either at the portal of entry or at different sites after systemic spread. Example - Clostridium tetani – at site of entry; Mycobacterium sp – spreads throughout the body and later becomes localized
  • Ingestion of toxins found outside the body example Botulism and Staphylococcal food poisoning

Mechanism of bacteria causing disease

  • Many bacteria produce toxins. Toxins are classified into Exotoxins and Endotoxins /Other bacterial products

S.No.

          Exotoxins

            Endotoxins

 Other   bacterial                     products

1.

  • Harmful
  • Complex lipopolysaccharides (LPS)
  • Components of cell wall of Gram-ve bacteria
  • Released on disintegration
  • LPS is a long chain toxic fatty acid (lipid A)connected to a core sugar chain
  • A carbohydrate chain is attached core sugar called O antigen which is used to serotype and differentiate bacteria
  • Hemolysins
  • Fibrinolysins
  • Coagulases
  • Hyaluronidases
  • End produts of septicaemia interferes with host metabolism
  • Cellular immune responses (hypersensitivity) leads to development of tuberculosis
  • Immune complex and immune mediated arthritis are caused by bacteria

2.

  • Enzymes produced by bacteria that interfere with host mechanism



3.

  • Produced within bacterial cytoplasm
  • Some are secreted through cell wall and are called “extracellular toxins

LPS causes severe systemic effects

  • Fever
  • Hypotension
  • Hemorrhage
  • Intravascular coagulation
  • Destruction of neutrophils
  • Release of enzymes


4.

  • Some are released only by lysis of cell wall called “Protoplasmic toxins or Prototoxins

  • LPS → Activate macrophages→ Produces cytokines like interleukin–1 (IL-1); tumour necrosis factor (TNF)


5.

  • Those that attack cells are called “Cytotoxins”
  • In circulating blood , LPS along with protein binds to CD14 molecules (present on the surface of macrophages and monocytes and acts as binding for LPS protein complex) on leukocytes, endothelial cells etc
  • LPS -protein complex acts on leucocytes
  • Produce cytokines → Pathological changes


6.

  • That attack neurons are called “Neurotoxic”

Example of specific neurotoxins are :

  • Tetanospasmin (Clostridium tetani)- blocks inhibitary transmitter substance
  • Botulinum (Cl. botulinum)-blocks cholinergic neurotransmitters
  • Alpha toxin (Cl. perfringens) -causes hemolysis and damages cell membrane -helps in spread of bacteria
  • Lethal toxin (Anthrax)-stimulates macrophages to produce free radicals and cytokines like interleukin and tumour necrosis factor which induce systemic shock and death
  • Exotoxins of anthrax bacilli and Escherichia coli causes ribosomal dysfunction leading to increase in cyclic AMP
  • In low doses LPS activates macrophages which eliminate bacteria
  • Activate complement- removal of bacteria
  • LPS also enhances release of TNF and interleukins in large amounts which sets up a local inflammatory response and eliminate infection
  • At higher levels of LPS, cytokine induces release of nitric oxide, platelet activating factor
  • Systemic effects like fever occurs
  • At still higher levels - septic shock or endotoxic shock due to systemic vasodilation, reduced cardiac output and activation of coagulation system resulting in Disseminated intravascular coagulation (DIC)


Attachment and entry of bacteria

  • Attachment of bacteria to the cell surfaces requires bacterial adhesins and cell receptors. Examples of bacterial adhesins are
    • Fimbrial proteins (Escherichia coli, Salmonella sp.)
    • Lipoteichoic acid (streptococci)
    • M protein and lipoteichoic acid (Fimbriae of streptoccoci)

Bacteria tropism

  • Fimbriae or pili in Gram negative bacteria are non flagellar filamentous structures
  • At the tips of the pili are minor protein components that determine to which host cells the bacteria will attach Example: Escherichia coli
  • Type L protein bind mannose (host receptor) causes urinary infection
  • Type P proteins bind galactose and causes pyelonephritis
  • Type S proteins bind sialic acid and causes meningitis
  • A single bacterium can express more than one pili or many pilar adhesins

Host receptor substances

  • Fibrinonectin (streptococci)
  • Mannose ( Escherichia coli )

Colonisation resistance

  • It is an important defence mechanism wherein attachment of bacterial adhesins is inhibited by normal microflora which occupy or block receptor sites by producing toxic metabolites and bacteriocins

Penetration

  • Some bacteria, reach the target cells and do not penetrate further (E.coli,Vibrio cholerae)
  • Others cross surface membranes after endocytosis by epithelial cells or go between cells (Salmonella, Brucella)
  • Inhaled facultative bacteria are taken up by macrophages and pass through lymphatics to lymphnodes and other tissues (Mycobacterium tuberculosis)
  • Cutaneous penetration occurs in skin injury or insect bites

Dissemination

  • It is helped by bacterial enzyme → collagenase, hyaluronidase and others

Growth

  • It is very important for all bacteria except that grows on food stuffs and produce toxins
  • Iron is a limiting nutrient
  • Bacterial ability to take away iron binding protein lactoferrin is a factor for virulence of bacteria
  • Gastric acidity is restricting factor for bacterial growth
  • Very high body temperature as in birds also limits bacterial growth (anthrax)
Last modified: Tuesday, 20 March 2012, 6:18 AM