Humans encounter bacteria, viruses and parasites that do not cause disease. An infection occurs when an organism invades the body and causes ill‐health.
| Term | Definition |
|---|---|
| Pathogen | An organism capable of causing disease |
| Commensal | An organism that is part of the normal flora |
| Pathogenicity | The capacity to cause disease |
| Virulence | The capacity to cause severe disease |
The capsule of Streptococcus pneumoniae is a pathogenicity determinant because acapsulate strains do not usually cause disease, but some capsular types cause more serious disease, i.e. they are more virulent (Chapter 19). The term parasite is often used to describe protozoan and metazoan organisms (see Chapters 49–52), but this is confusing as these organisms may be either pathogens or commensals.
Types of pathogen
Obligate pathogens are always associated with disease (e.g. Treponema pallidum and HIV) i.e., their presence is diagnostic and usually requires action. Some pathogens may cause disease if the conditions are right. For example, Bacteroides fragilis is a gut commensal, but if it accesses the peritoneal cavity through perforation of the viscus it causes severe infection and peritonitis. Opportunistic pathogens usually cause infection when the host defences are compromised. For example, Pneumocystis jiroveci usually causes lung infection only in a host who has severely compromised T‐cell immunity.
Mechanisms of pathogenicity
The process of infection has several stages.
Access to the host: transmission
Organisms are transmitted by various means, but most are adapted to a particular route such as respiratory pathogens. Strains may develop epidemic potential by developing adaptation to an environment that either favours transmission or better survival, for example, most respiratory pathogens induce coughing that facilitates their spread, expelling aerosols of organisms in respiratory droplets. Vomiting and diarrhoea associated with organisms that are spread by the faecal–oral route increases environmental contamination and increases the risk of transmission.
Attachment to the host
Microorganisms attach themselves to host tissues to colonize them, and each species employs a different strategy. The distribution of the receptors to which a particular organism can bind will define the organs that it will infect (its tissue tropism) as in the following examples.
Neisseria gonorrhoeae adheres to the genital mucosa using fimbriae.
Influenza virus attaches to the respiratory mucosa by its haemagglutinin antigen accounting for its species‐specific pathogenesis (the ability of certain strains to cause disease in a particular species, such as avian or porcine strains) and intraspecies variation in affinity and susceptibility (Chapter 40).
Bacterial biofilms aid colonization of indwelling prosthetic devices, such as catheters and the respiratory tract. Some strains of staphylococci have genes that mediate attachment to plastics and to the biological molecules that coat intravascular devices.
Mucosal destruction by viruses may expose a variety of host molecules such as fibronectin, vibronectin and collagen to which invading organisms can bind.
Invasion
Some bacteria have mechanisms that help them get close to the mammalian epithelium. For example, Vibrio cholerae excretes a mucinase to help it reach the enterocyte. Microorganisms have a variety of strategies that allow them to cross mucosal barriers or different types of cell membrane.
Motility
The ability to move in order to locate new sources of food or in response to chemotactic signals enhances pathogenicity. V. cholerae is motile by virtue of its flagellum, and is more virulent than non‐motile strains.
Immune evasion
To survive in the human host, pathogens must overcome the host immune defences.
Respiratory bacteria secrete an IgA protease that degrades host immunoglobulin in the mucosa.
Staphylococcus aureus expresses protein A, which binds host immunoglobulin, preventing opsonization and complement activation.
S. pneumoniae has a polysaccharide capsule, which inhibits phagocytosis by polymorphonuclear neutrophils.
Toxoplasma gondii, Leishmania donovani and Mycobacterium tuberculosis are adapted to survive the killing mechanisms of macrophages by different mechanisms.
The lipopolysaccharide (LPS) of Gram‐negative organisms makes them resistant to the effect of complement.
Trypanosoma alter surface antigens to evade the adaptive humoral immune response.
Damaging the host
Toxins
Endotoxins
Endotoxins exert their effect through host mechanisms by, for example, stimulating macrophages to produce cytokines such as interleukin‐1 (IL‐1) and tumour necrosis factor (TNF) that lead to fever and shock (see Chapter 55).
Exotoxins
Bacterial exotoxins can cause local or distant damage. They are usually proteins and may have a subunit structure.
Cholera toxin B subunit binds to the epithelial cell and the A subunit activates adenyl cyclase, which results in sodium and chloride efflux from the cell, thus causing diarrhoea.
Staphylococcal enterotoxins act as superantigens, causing non‐specific activation of T‐cells that result in intense cytokine production leading to fever, shock, gastrointestinal disturbance and rash (toxic shock syndrome).
Diphtheria toxin and Pseudomonas aeruginosa exotoxin A stop protein synthesis by blocking peptide chain elongation.
Clostridial toxins interfere with host functions, e.g. neurological or neuromuscular signalling in botulism or tetanus.Neutralizing toxin with antibody may ameliorate the damaging effects, e.g. human‐tetanus immunoglobulin (see Chapter
