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Chapter: Pharmaceutical Microbiology : Principles Of Microbial Pathogenicity And Epidemiology

The part of the body that is most widely exposed to microorganisms is the skin. Intact skin is usually impervious to microorganisms, and its surface is of acid pH and contains relatively few nutrients that are favourable for microbial growth.





The part of the body that is most widely exposed to microorganisms is the skin. Intact skin is usually impervious to microorganisms, and its surface is of acid pH and contains relatively few nutrients that are favourable for microbial growth. The vast majority of organisms falling on to the skin surface will die, while the survivors must compete with the commensal microflora for nutrients in order to grow. These commensals, which include coryneform bacteria, staphylococci and yeasts, derive nutrients from compounds like urea, hormones (e.g. testosterone) and fatty acids found in the apocrine and epocrine secretions. Such organisms are highly adapted to growth in this environment and will normally prevent the establishment of chance contaminants of the skin. Infections of the skin itself, such as ringworm (Trichophyton mentagrophytes) and warts (human papillomavirus, HPV), rarely, if ever, involve penetration of the epidermis. Infection can, however, occur through the skin following trauma such as burns, cuts and abrasions and, in some instances, through insect or animal bites or the injection of contaminated medicines. In recent years extensive use of intravascular and extravascular medical devices and implants has led to an increase in the occurrence of hospital-acquired infection. Commonly, these infections involve the growth of skin commensals such as Staph. epidermidis when associated with devices that penetrate the skin barrier. The organism grows as an adhesive biofilm on the surfaces of the device, and infection arises either from contamination of the device during its implantation or by growth along it of the organism from the skin. In such instances the biofilm sheds bacterial cells to the body and may give rise to a bacteraemia (the presence of bacteria in the blood).


The weak spots, or Achilles heels, of the body occur where the skin ends and mucous epithelial tissues begin (mouth, anus, eyes, ears, nose and urinogenital tract).These mucous membranes present a much more favourable environment for microbial growth than the skin, in that they are warm, moist and rich in nutrients. Such membranes, nevertheless, possess certain characteristics that allow them to resist infection. Most of them, for example, possess their own highly adapted microbiotas which reduce the chances of infection by any invading organisms through a process termed colonization resistance. The resident flora varies greatly between different sites of the body, but is usually common to particular host species. Each site can be additionally protected by physicochemical barriers such as extreme acid pH in the stomach and bile salts in the large bowel, the presence of freely circulating non-specific antibodies and/or opsonins, and/or by macrophages and phagocyte. All infections start from contact between these tissues and the potential pathogen. Contact may be direct, from an infected individual to a healthy one; or indirect, and may involve inanimate vectors such as soil, food, drink, air and airborne particles. These may directly contact the body or be ingested or inhaled or enter wounds via infected bed linen and clothing. Indirect contact may also involve animal vector intermediates (carriers).




Air contains a large amount of suspended organic matter and, in enclosed occupied spaces, may hold up to 1000 microorganisms/m3. Almost all of these airborne organisms are non-pathogenic bacteria and fungi, of which the average person inhales approximately 10 000/day. The respiratory tract is protected against this assault by a mucociliary blanket that envelops the upper respiratory tract and nasal cavity. Both present a tortuous path down which microbial particles travel and impact on these surfaces to become trapped within an enveloping blanket of mucus. Beating cilia move the mucus coating to the back of the throat where it, together with adherent particles, is swallowed. The alveolar regions of the lower respiratory tract have additional protection in the form of alveolar macrophages. To be successful, a pathogen must avoid being trapped in the mucus and swallowed; if deposited in the alveolar sacs it must avoid phagocytosis by macrophages, or if phagocytosed it must resist subsequent digestion by them. The possession of surface adhesins, specific for epithelial receptors, aids attachment of the invading microorganism and avoidance of removal by the mucociliary blanket. Other strategies include the export of ciliostatic toxins (i.e. Corynebacterium diphtheriae) that paralyse the cilial bed. As the primary defence of the respiratory tract is the mucociliary blanket, it is easy to envisage how infection with respiratory viruses (i.e. influenza virus, which kills respiratory epithelia) or the chronic inhalation of tobacco smoke, which increases mucin production and decreases the proportion of ciliated epithelial cells, increases the susceptibility of individuals to infection.




The intestinal tract must contend with whatever it is given in terms of food and drink. The extreme acidity and presence of digestive enzymes in the stomach will kill many of the bacteria challenging it, and the gastrointestinal tract carries its own commensal flora of yeast and lactobacilli that afford protection by, for example, competing with potential pathogens like Helicobacter pylori. Bile salts are mixed with the semidigested solids exiting from the stomach into the small intestine. These salts not only neutralize the stomach acids but also represent biological detergents or surfactants that are able to solubilize the outer membrane of many Gram-negative bacteria. Consequently, the small intestine is normally colonized by lower numbers of bacteria than the colon. The lower gut on the other hand is highly populated by commensal microorganisms (10 12 g−1 gut tissue) that are often associated with the intestinal wall, either embedded in layers of protective mucus or attached directly to the epithelial cells or attached to particulate food residues. The pathogenicity of incoming bacteria and viruses depends on their ability to survive passage through the stomach and duodenum and their capacity for attachment to, or penetration of, the gut wall, despite competition from the commensal flora and the presence of secretory antibodies . 




In healthy individuals, the bladder, ureters and urethra are sterile, and sterile urine constantly flushes the urinary tract. Organisms invading the urinary tract must avoid being detached from the epithelial surfaces and washed out during urination. Because the male urethra is long (c.20 cm), bacteria must be introduced directly into the bladder, possibly through catheterization, in order to initiate an infection. The female urethra is much shorter (c.5 cm) and is more readily traversed by microorganisms that are normally resident within the vaginal vault. Bladder infections are therefore much more common in the female. Spread of the infection from the bladder to the kidneys can easily occur through reflux of urine into the ureter. As for the implantation of devices across the skin barrier (above), longterm catheterization of the bladder will promote the occurrence of bacteriuria (the presence of bacteria in the urine) with all of the associated complications.


Lactic acid in the vagina gives it an acidic pH (5.0); this, together with other products of metabolism, inhibits colonization by most bacteria, except some lactobacilli that constitute the commensal flora. Other types of bacteria are unable to establish themselves in the vagina unless they have become extremely specialized. These species of microorganism tend to be associated with sexually transmitted infections.




The conjunctiva is usually free of microorganisms and protected by the continuous flow of secretions from lachrymal and other glands, and by frequent mechanical cleansing of its surface by the eyelid periphery during blinking. Lachrymal fluids contain a number of inhibitory compounds, together with lysozyme, that can enzymically degrade the peptidoglycan of Gram-positive bacteria such as staphylococci. Damage to the conjunctiva, caused through mechanical abrasion or reductions in tear flow, will increase microbial adhesion and allow colonization by opportunist pathogens. The likelihood of infection is thus promoted by the use of soft and hard contact lenses, physical damage, exposure to chemicals, or damage and infection of the eyelid border (blepharitis).


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