Entry, exit and transmission

13 Entry, exit and transmission


Microorganisms must attach to, or penetrate, the host’s body surfaces

The mammalian host can be considered as a series of body surfaces (Fig. 13.1). To establish themselves on or in the host, microorganisms must either attach to, or penetrate, one of these body surfaces. The outer surface, covered by skin or fur, protects and isolates the body from the outside world, forming a dry, horny, relatively impermeable outer layer. Elsewhere, however, there has to be more intimate contact and exchange with the outside world. Therefore, in the alimentary, respiratory and urogenital tracts, where food is absorbed, gases exchanged and urine and sexual products released, respectively, the lining consists of one or more layers of living cells. In the eye, the skin is replaced by a transparent layer of living cells, the conjunctiva. Well-developed cleansing and defence mechanisms are present at all these body surfaces, and entry of microorganisms always has to occur in the face of these natural mechanisms. Successful microorganisms therefore possess efficient mechanisms for attaching to, and often traversing, these body surfaces.

Sites of entry


Microorganisms gaining entry via the skin may cause a skin infection or infection elsewhere

Microorganisms which infect or enter the body via the skin are listed in Table 13.1. On the skin, microorganisms other than residents of the normal flora (see Ch. 8) are soon inactivated, especially by fatty acids (skin pH is about 5.5), and probably by substances secreted by sebaceous and other glands, and certain peptides formed locally by keratinocytes protect against invasion by group A streptococci. Materials produced by the normal flora of the skin also protect against infection. Skin bacteria may enter hair follicles or sebaceous glands to cause styes and boils, or teat canals to cause staphylococcal mastitis.

Table 13.1 Microorganisms that infect via the skin

Microorganism Disease Comments
Arthropod-borne viruses Various fevers 150 distinct viruses, transmitted by bite of infected arthropod
Rabies virus Rabies Bite from infected animals
Human papillomaviruses Warts Infection restricted to epidermis
Staphylococci Boils Commonest skin invaders
Rickettsia Typhus, spotted fevers Infestation with infected arthropod
Leptospira Leptospirosis Contact with water containing infected animals’ urine
Streptococci Impetigo, erysipelas Concurrent pharyngeal infection in one-third of cases
Bacillus anthracis Cutaneous anthrax Systemic disease following local lesion at inoculation site
Treponema pallidum and T. pertenue Syphilis, yaws Warm, moist skin susceptible
Yersinia pestis, Plasmodia Plague, malaria Bite from infected rodent flea or mosquito
Trichophyton spp. and other fungi Ringworm, athlete’s foot Infection restricted to skin, nails, hair
Ancylostoma duodenale (or Necator americanus) Hookworm Silent entry of larvae through skin of, e.g. foot
Filarial nematodes Filariasis Bite from infected mosquito, midge, blood-sucking fly
Schistosoma spp. Schistosomiasis Larvae (cercariae) from infected snail penetrate skin during wading or bathing

Some remain restricted to the skin (papillomaviruses, ringworm), whereas others enter the body after growth in the skin (syphilis) or after mechanical transfer across the skin (arthropod-borne infections, schistosomiasis).

Several types of fungi (the dermatophytes) infect the non-living keratinous structures (stratum corneum, hair, nails) produced by the skin. Infection is established as long as the parasites’ rate of downward growth into the keratin exceeds the rate of shedding of the keratinous product. When the latter is very slow, as in the case of nails, the infection is more likely to become chronic.

Wounds, abrasions or burns are more common sites of infection. Even a small break in the skin can be a portal of entry if virulent microorganisms such as streptococci, water-borne leptospira or blood-borne hepatitis B virus are present at the site. A few microbes, such as leptospira or the larvae of Ancylostoma and Schistosoma, are able to traverse the unbroken skin by their own activity.

Biting arthropods

Biting arthropods such as mosquitoes, ticks, fleas and sandflies (see Ch. 27) penetrate the skin during feeding and can thus introduce infectious agents or parasites into the body. The arthropod transmits the infection and is an essential part of the life cycle of the microorganism. Sometimes the transmission is mechanical, the microorganism contaminating the mouth parts without multiplying in the arthropod. In most cases, however, the infectious agent multiplies in the arthropod and, as a result of millions of years of adaptation, causes little or no damage to that host. After an incubation period, it appears in the saliva or faeces and is transmitted during a blood feed. The mosquito, for instance, injects saliva directly into host tissues as an anticoagulant, whereas the human body louse defecates as it feeds, and Rickettsia rickettsii, which is present in the faeces, is introduced into the bite wound when the host scratches the affected area.

The conjunctiva

The conjunctiva can be regarded as a specialized area of skin. It is kept clean by the continuous flushing action of tears, aided every few seconds by the windscreen wiper action of the eyelids. Therefore, the microorganisms that infect the normal conjunctiva (chlamydia, gonococci) must have efficient attachment mechanisms (see Ch. 25). Interference with local defences due to decreased lacrimal gland secretion or conjunctival or eyelid damage allows even non-specialist microorganisms to establish themselves. Contaminated fingers, flies, or towels carry infectious material to the conjunctiva, examples including herpes simplex virus infections leading to keratoconjunctivitis or chlamydial infection resulting in trachoma. Antimicrobial substances in tears, including lysozyme, an enzyme, and certain peptides have a defensive role.

Respiratory tract

Some microorganisms can overcome the respiratory tract’s cleansing mechanisms

Air normally contains suspended particles, including smoke, dust and microorganisms. Efficient cleansing mechanisms (see Chs 18 and 19) deal with these constantly inhaled particles. With about 500–1000 microorganisms/m3 inside buildings, and a ventilation rate of 6    l/min at rest, as many as 10 000 microorganisms/day are introduced into the lungs. In the upper or lower respiratory tract, inhaled microorganisms, like other particles, will be trapped in mucus, carried to the back of the throat by ciliary action, and swallowed. Those that invade the normal healthy respiratory tract have developed specific mechanisms to avoid this fate.

Interfering with cleansing mechanisms

The ideal strategy is to attach firmly to the surfaces of cells forming the mucociliary sheet. Specific molecules on the organism (often called adhesins) bind to receptor molecules on the susceptible cell (Fig. 13.2). Examples of such respiratory infections are given in Table 13.2.

Inhibiting ciliary activity is another way of interfering with cleansing mechanisms. This helps invading microorganisms establish themselves in the respiratory tract. B. pertussis, for instance, not only attaches to respiratory epithelial cells, but also interferes with ciliary activity, while other bacteria (Table 13.3) produce various ciliostatic substances of generally unknown nature.

Table 13.3 Interference with ciliary activity in respiratory infections

Cause Mechanisms Importance
Infecting bacteria interfere with ciliary activity (B. pertussis, H. influenzae, P. aeruginosa, M. pneumoniae) Production of ciliostatic substances (tracheal cytotoxin from B. pertussis, at least two substances from H. influenzae, at least seven from P. aeruginosa) + +
Viral infection Ciliated cell dysfunction or destruction by influenza, measles + + +
Atmospheric pollution (automobiles, cigarette smoking) Acutely impaired mucociliary function ? +
Inhalation of unhumidified air (indwelling tracheal tubes, general anaesthesia) Acutely impaired mucociliary function +
Chronic bronchitis, cystic fibrosis Chronically impaired mucociliary function + + +

Although microbes can actively interfere with ciliary activity (first item), a more general impairment of mucociliary function also acts as a predisposing cause of respiratory infection.

Gastrointestinal tract

Some microorganisms can survive the intestine’s defences of acid, mucus and enzymes

Apart from the general flow of intestinal contents, there are no particular cleansing mechanisms in the intestinal tract, except insofar as diarrhea and vomiting can be included in this category. Under normal circumstances, multiplication of resident bacteria is counterbalanced by their continuous passage to the exterior with the rest of the intestinal contents. Ingestion of a small number of non-pathogenic bacteria, followed by growth in the lumen of the alimentary canal, produces only relatively small numbers within 12–18    h, the normal intestinal transit time.

Infecting bacteria must attach themselves to the intestinal epithelium (Table 13.4) if they are to establish themselves and multiply in large numbers. They will then avoid being carried straight down the alimentary canal to be excreted with the rest of the intestinal contents. The concentration of microorganisms in faeces depends on the balance between the production and removal of bacteria in the intestine. Vibrio cholerae (Figs 13.3, 13.4) and rotaviruses both establish specific binding to receptors on the surface of intestinal epithelial cells. For V. cholerae, establishment in surface mucus may be sufficient for infection and pathogenicity. The fact that certain microbes infect mainly the large bowel (Shigella spp.) or small intestine (most salmonellae, rotaviruses) indicates the presence of specific receptor molecules on mucosal cells in these sections of the alimentary canal.

Infection sometimes involves more than mere adhesion to the luminal surface of intestinal epithelial cells. Shigella flexneri, for example, can only enter these cells from the basal surface. Initial entry occurs after uptake by M cells, and the bacteria then invade local macrophages. This gives rise to an inflammatory response with an influx of polymorphs, which in turn causes some disruption of the epithelial barrier. Bacteria can now enter on a larger scale from the intestinal lumen and invade epithelial cells from below. The bacteria enhance their entry by exploiting the host’s inflammatory response.

Mechanisms to counteract mucus, acids, enzymes and bile

Successful intestinal microbes must counteract or resist mucus, acids, enzymes and bile

Mucus protects epithelial cells, perhaps acting as a mechanical barrier to infection. It may contain molecules that bind to microbial adhesins, therefore blocking attachment to host cells. It also contains microbe-specific secretory IgA antibodies, which protect the immune individual against infection. Motile microorganisms (V. cholerae, salmonellae and certain strains of E. coli) can propel themselves through the mucus layer and are therefore more likely to reach epithelial cells to make specific attachments; V. cholerae also produces a mucinase, which probably helps its passage through the mucus. Non-motile microorganisms, in contrast, rely on random and passive transport in the mucus layer.

As might be expected, microorganisms that infect by the intestinal route are often capable of surviving in the presence of acid, proteolytic enzymes and bile. This also applies to microorganisms shed from the body by this route (Table 13.5).

Table 13.5 Microbial properties that aid success in the gastrointestinal tract

Property Examples Consequence
Specific attachment to intestinal epithelium Poliovirus, rotavirus, Vibrio cholerae Microorganism avoids expulsion with other gut contents and can establish infection
Motility V. cholerae, certain E. coli strains Bacteria travel through mucus and are more likely to reach susceptible cell
Production of mucinase V. cholerae May assist transit through mucus (neuraminidase)
Acid resistance Mycobacterium tuberculosis Encourages intestinal tuberculosis (acid labile microorganisms depend on protection in food bolus or in diluting fluid) increased susceptibility in individuals with achlorhydria
  Helicobacter pylori Establish residence in stomach
  Enteroviruses (hepatitis A, poliovirus, coxsackieviruses, echoviruses) Infection and shedding from gastrointestinal tract
Bile resistance Salmonella, Shigella, enteroviruses Intestinal pathogens
  Enterococcus faecalis, E. coli, Proteus, Pseudomonas Establish residence
Resistance to proteolytic enzymes Reoviruses in mice Permits oral infection
Anaerobic growth Bacteroides fragilis Most common resident bacteria in anaerobic environment of colon

All organisms infecting by the intestinal route must run the gauntlet of acid in the stomach. Helicobacter pylori has evolved a specific defence (Box 13.1). The fact that tubercle bacilli resist acid conditions favours the establishment of intestinal tuberculosis, but most bacteria are acid sensitive and prefer slightly alkaline conditions. For instance, volunteers who drank different doses of V. cholerae contained in 60    mL saline showed a 10 000-fold increase in susceptibility to cholera when 2    g of sodium bicarbonate was given with the bacteria. The minimum disease-producing dose was 108 bacteria without bicarbonate and 104 bacteria with bicarbonate. Similar experiments have been carried out in volunteers with Salmonella typhi, and the minimum infectious dose of 1000–10 000 bacteria was again significantly reduced by the ingestion of sodium bicarbonate. Infective stages of protozoa and worms resist stomach acid because they are protected within cysts or eggs.

imageBox 13.1 Lessons in microbiology

How to survive stomach acid: the neutralization strategy of Helicobacter pylori.

This bacterium was discovered in 1983, and was shown to be a human pathogen when two courageous doctors, Warren and Marshall in Perth, Western Australia, drank a potion containing the bacteria and developed gastritis. The infection spreads from person to person by the gastro–oral or fecal–oral route, and 150    years ago, nearly all humans were infected as children. Today, in countries with improved hygiene, this is put off until later in life, until at the age of 50 more than half of the population have been infected. The clinical outcome includes peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma and host, bacterial and environmental factors are thought to be involved. Genetic susceptibility is implicated in both acquiring and clearing H. pylori (HP) infection. After being eaten, the bacteria have a number of strategies resulting in adaptation to the host gastric mucosa having attached by special adhesins to the stomach wall. These include host mimicry leading to evasion of the host response and genetic variation. Most microbes (e.g. V. cholerae) are soon killed at the low pH encountered in the stomach. H. pylori, however, protects itself by releasing large amounts of urease, which acts on local urea to form a tiny cloud of ammonia round the invader. The attached bacteria induce apoptosis in gastric epithelial cells, as well as inflammation, dyspepsia and occasionally a duodenal or gastric ulcer, so that treatment of these ulcers is by antibiotics rather than merely antacids. Some 90% of duodenal ulcers are due to HP infection, and the rest to aspirin or NSAIDs. The bacteria do not invade tissues, and they stay in the stomach for years, causing asymptomatic chronic gastritis. Up to 3% of infected individuals develop chronic active gastritis and progress to intestinal metaplasia which can lead to stomach cancer. H. pylori was the third bacterium for which the entire genome was sequenced; several gene products have been characterized and key developments include understanding the genetic variation of genes encoding the outer membrane proteins and host adaptation.

When the infecting microorganism penetrates the intestinal epithelium (Shigella, S. typhi, hepatitis A and other enteroviruses) the final pathogenicity depends upon:

Urogenital tract

Vaginal defences

The vagina has no particular cleansing mechanisms, and repeated introductions of a contaminated, sometimes pathogen-bearing foreign object (the penis), makes the vagina particularly vulnerable to infection, forming the basis for sexually transmitted diseases (see Ch. 21). Nature has responded by providing additional defences. During reproductive life, the vaginal epithelium contains glycogen due to the action of circulating estrogens, and certain lactobacilli colonize the vagina, metabolizing the glycogen to produce lactic acid. As a result, the normal vaginal pH is about 5.0, which inhibits colonization by all except the lactobacilli and certain other streptococci and diphtheroids. Normal vaginal secretions contain up to 108/mL of these commensal bacteria. If other microorganisms are to colonize and invade they must either have specific mechanisms for attaching to vaginal or cervical mucosa or take advantage of minute local injuries during coitus (genital warts, syphilis) or impaired defences (presence of tampons, estrogen imbalance). These are the microorganisms responsible for sexually transmitted diseases.

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Jul 9, 2017 | Posted by in MICROBIOLOGY | Comments Off on Entry, exit and transmission

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