Antimicrobial Chemotherapy and Virulence Factors Lecture Notes PDF

Antimicrobial Chemotherapy and Virulence Factors By Dr Sahar Ali Mohamed Profssor of Medical Microbiology & Immunology Department-Faculty of Medicine-Menoufia University  OBJECTIVES Definitions Ideal antimicrobial agent Mechanisms of actions of differe...

Antimicrobial Chemotherapy and Virulence Factors By Dr Sahar Ali Mohamed Profssor of Medical Microbiology & Immunology Department-Faculty of Medicine-Menoufia University  OBJECTIVES Definitions Ideal antimicrobial agent Mechanisms of actions of different groups of antibiotics Complications of antimicrobial agents Mechanisms of antimicrobial resistance Chemoprophylaxis Virulance factors of bacteria Bactericidal drugs: drugs have the ability to kill the bacteria. Bacteriostatic agents: drugs that can only inhibit bacterial multiplication without killing them.  Broad-spectrum antibiotics: They are active against several types of microorganisms Narrow-spectrum antibiotics: They are active against one or very few types of bacteria. Selective toxicity: achieved by difference between metabolism and structure of bacteria and the corresponding in the human cell.  Ideal antimicrobial agent  has high Selective toxicity: harmful to the bacteria and non toxic to the host cells. Broad spectrum:rather than narrow spectrum.  Bactericidal better than bacteriostatic.  Diffusible to distant body areas with slow rate of excretion.  Bacteria do not develop resistance to it. Not associated with complication. Mechanisms of action of antimicrobial agents  Mechanisms of action of antimicrobial agents 1-Inhibition of bacterial cell wall synthesis. 2-Inhibition of bacterial cell membrane function. 3-Inhibition of bacterial protein synthesis. 4-Inhibition of bacterial nucleic acid synthesis. 5-Competitive inhibition. The drug compete with essential metabolite in the bacteria. Mechanism of action Drugs 1-Inhibition of cell wall synthesis B-Lactam drugs as Inhibition of Peptidoglycan synthesis penicillin- Non-B-Lactam drugs as: vancomycin- 2-Inhibition of protein synthesis Chloramphenicol- Aminoglycosides 3-Inhibition of nucleic acid synthesis Cipro Inhibition of DNA syntheses enzyme 4-Alteration of cell membrane function 5-Competitive inhibition : Drugs Sulfonamides compete for enzymes needed for compete with PABA  Mechanisms of resistance to antimicrobial agents 1- Bacteria produce enzymes that inactivate the drug. 2- Bacteria block entry and decrease permeability to the drug. 3- Bacteria alter the target site for drug action. 4- Bacteria actively pump the drug out= efflux pump Resistance to Antibiotics  Classification of bacteria Saprophytic bacteria: They live freely in nature – pathogenic bacteria: - causing tissue damage leading to diseases. Commensals: FLORA live in the external or internal surface of the body without causing disease. (normal body flora).may be beneficial to the host  Opportunistic pathogen: Some commensal bacteria capable of causing disease only under certain conditions such as: 1- Lowered host immune mechanisms e.g. immunosuppressed patients. 2- Change in the natural habitat of the organism.  Bacterial Virulence Factors definition: Certain structures or product that helps bacteria to cause disease Virulence Factors are 1-Adherence factors 2-Antiphagocytic factors 3--Antigenic variation 4- Toxin production Bacterial Virulence Factors  1. Adherence Factors Bacterial attachment to host cell by 1-Ordinary pili : Pili of Neisseria gonorrhoeae and E. coli help the attachment to – urinary tract epithelium. –  2-Antiphagocytic Factors Capsule: prevents phagocytosis e.g. S. pneumoniae. Cell wall proteins -Protein A of S. aureus  3-Antigenic Heterogenicity (variation) Bacteria change antigenicity of their surface as in (N. gonorrhea -Borrelia) to escape immune response N.gonorrhea Altering the Adhesive Tips of Their Pili  Exotoxins and Endotoxins Character 1-Exotoxins 2-Endotoxins The gene Plasmid Bacterial chromosome location Chemical nature Proteins Lipopolysaccharides Action Specific Non-specific Production Secreted by living cells Integral part of the cell wall (released after cell death) Bacteria type Gram Positive or Gram Negative negative