Bacterial Pathogenesis

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Understand co-existence with microorganisms from an evolutionary and medical perspective

  • Mutualism - Such as a person and a dog
  • Commensalism - OMD Definition
  • Parasitism - One organism benefits and the other is hurt; aka infection

Entry points for microbes of the four virulence levels

Group 1

  • Specific mechanisms for attaching and sometimes penetrating the healthy host
  • Mediated by adhesins
  • e.g., Common cold

Group 2

Group 3

  • Requirement for breach of skin or mucosa to gain entry, including large bites
  • e.g., Rabies, oropharyngeal anaerobes

Group 4

  • Requirement for local or general defect in body defenses
  • e.g., Opportunistic infections such as Pneumocystis carinii

Defense mechanisms by system

Skin

  • Largest organ (5 Kg)
  • Covered in hairs and an outer layer of dead cells (shed at a rate of approximately 5000 squames/second)
  • Most infections transmitted where there are living cells (except the dermatophytes)
    • A layer of mucin gel protects these interfaces
  • Commensal organisms metabolize sebum to fatty acids of pH5.5, which inhibits most microorganisms
  • Skin trauma may be microscopic or macroscopic (needlesticks, shaving, cuts and scrapes, insect bites, reptile/mammalian bites.)

Oropharynx

  • Is cleaned by saliva and drinking
  • Oral mucosa and teeth are resistant to some infections, such as Neisseria gonorrhoea
  • Streptococcus mutans has enzyme glycosyl transferase, which synthesizes glucan (an adhesive for bacteria to teeth) from sucrose
  • Plaque contains 109 bacteria/g, pH about
  • Bacteria at the gingival margins (largely anaerobic) are at the highest concentration in the body (1012/litre)
  • Caries, periodontal disease, halitosis
  • Submucosal lymphoid tissue: laryngeal/pharyngeal tonsils and at back of throat.

Respiratory Tract

  • Air contains ~400-900 microbes per m3, most of which is exhaled
  • Chickenpox and tuberculosis are the main airborne pathogens
  • Most infections are caused by respiratory viruses transmitted by direct contact and by upper respiratory bacterial commensal flora
  • Protective features consist of the mucociliary blanket and escalator
  • The lower respiratory tract is equipped with alveolar macrophages
  • Special problems: cigarette smoking, COPD, asbestosis, cystic fibrosis.

Gastrointestinal Tract

  • No cleansing mechanisms except for enhanced peristalsis ? secretion (diarrhoea and vomiting)
  • Protected by mucus layer and acid conditions in stomach, bile, Peyer's patches and possibly anal glands
  • Gastrointestinal pathogens (Salmonella, Shigella, Campylobacter species, and Yersinia enterocolitica) may be buffered by food
  • Profuse flora, particularly at distal end, are largely anaerobic and bile resistant

Urogenital Tract

  • Urine is normally sterile
  • Skin flora in the distal urethra is regularly flushed by micturition
  • Males are protected by longer urethra and by antibacterial substances in prostatic secretions
  • Urethral pathogens (uropathogenic Escherichia coli, Neisseria gonorrhoea) must be capable of firm attachment, usually via pili
  • Transitional epithelium of bladder can respond to infection with inflammation and secretory antibody production
  • Ureters close under pressure at the bladder trigone to prevent reflux which can cause renal infection (pyelonephritis)
  • Infection of the urinary tract is often associated with pregnancy, stones or tumors
  • During the reproductive years, vaginal epithelium contains glycogen as a result of estrogens
  • Lactobacilli in the vagina (108/ml) ferment the glycogen to lactic acid, which maintains vaginal pH at about 5
  • This is only optimal for lactobacilli
  • Semen contains alakalizing substances to preserve sperm motility
  • This decreases the vagina's natural acidic state and lowers its resistance to infections
  • sexually transmitted infections are usually introduced at the same time
  • Mucus in the cervix presents a barrier to the uterus, which is itself equipped with ciliated endometrium
    • Aside from occasional accidents such as water skier's douche, access of infection to the uterine (Fallopian) tubes is theorized to occur via adherence to spermatozoa

Microbial spread within the body

Methods of infection containment

  • a requirement for a specific cell type (e.g., Rhinoviruses)
  • temperature specificity (e.g., Mycobacterium leprae)
  • by anatomical barriers (e.g., basement membranes, endothelium, fascial planes, tendon sheaths, the omentum)
  • by the inflammatory and immune systems of the body
  • Highly vascular tissues are much more resistant to infection than tissues with a poor blood supply

Methods of microorganism spread

  • direct invasion of adjacent tissues
  • via lymphatic channels
  • the bloodstream and along the nerves

Determinants of spread throughout the body

  • intrinsic invasiveness of the infecting organism
  • the organism's multiplication rate
  • ability to evade or engage the defense mechanisms of the host

Exit of microbes from the body

  • Sewage has eliminated (for many people) what was the most potent means of dissemination
  • Fecal-oral spread remains of major importance
  • Respiratory spread is responsible for a huge number of infections
  • Sexual transmission
  • Dissemination via contamination of the environment from the corpses of infected hosts (e.g., Anthrax, African haemorrhagic fevers, Ebola and Marburg)
  • Medical advances have created new opportunities for microbes to disseminate (e.g., blood transfusions and organ transplants)