PATHOGENICITY OF MICROORGANISMS Some microorganisms are : 1- Harmless microorganism, as normal flora 2- Harmfull microorganism, as pathogenic. A pathogenic microorganism is defined as one that causes or is capable of causing disease by production of toxic, or by colonization on the skin or mucous membrane, or by being introduced into a normally sterile body site, or by infection of an immunocompromised host. Microbial colonization may result in;- 1- elimination of the microorganisms without affecting the host. 2- infection in which the organisms multiply and causes the host to react by making an immune or other type of response. 3- Infectious diseases occurs when the organism causes tissue damage and impaired of the body function. BACTERIAL PATHOGENESIS The infectious process can be divided into several stages: 1- Entry into the host, with evasion of host primary defenses 2- Adhesion of the microorganism to host cells 3- Propagation of the organism 4- Damage to host cells by bacterial toxins or an inflammatory response of 'the host 5- Evasion of host secondary defenses Pathogenicity of a microorganism depends on its success in completing some or all of these stages. The characteristics of pathogenic microorganism are virulence factors, antigenic switching and infections in human populations. 1
A. Virulence factors Virulence factors are those characteristics of a bacterium that enhance its pathogenicity, that is, the ability to cause disease. The more important classes of virulence factors are: 1- Entry into the host 2- Adherence to host cells 3- Invasiveness 4- Bacterial toxins 1- Entry into the host: By one of several parts: the respiratory tract, gastrointestinal tract (GI), urogenital tract, or skin that has been cut, punctured, or burned. Once entry is achieved, the pathogen must overcome a diversity of host defenses before it can establish itself, include primary host defenses: 1- phagocytosis, 2- the acidic environments of the stomach and urogenital tract. 3- various hydrolytic and proteolytic enzymes found in the saliva, stomach, and small intestine. Bacteria that have an outer polysaccharide capsule ( for example Streptococcus pneumonia and Neisseria meningitidis) have a better chance of surviving these primary host defenses. 2- Adherence to host cells: This done by: pili like Escherichia coli, or fimbriae like group A Streptococcus, or by cell surface adhesion molecules or by particularly hydrophobia cell walls (Figure 2). In each case, adherence enhances virulence by preventing the bacteria from being carried away by mucus, or washed from organs with fluid flow (the urinary and the GI tracts) and allows each attached bacterial cell to form a microcolony. Neisseria gonorrhoea in which strains that lack pili are not pathogenic. 2
3- Invasiveness: Invasive bacteria are those that can enter host cells or penetrate mucosal surfaces, spreading from the initial site of infection, by several bacterial enzymes, like collagenase and hyaluronidase, which degrade components of the extracellular matrix, providing the bacteria with easier access to host cell surfaces. Invasion is followed by inflammation, depending on the organism, which can be either : - pyogenic (involving pus formation contains neutrophils). - granulomatous (having nodular lesions contain fibroblasts, lymphocytes, and macrophages). 4- Bacterial toxins: Some bacteria cause disease by producing toxins, the exotoxins and the endotoxins. a. Exotoxins: are proteins, are secreted by both G+ and G bacteria, are heat labile or heat stable, find in G+ or G- bacteria, caused septic shock syndrome but not severe,e.g. diphtheria, shigella, cholera,, tetanus exotoxin. one microgram of tetanus exotoxin (produced by Clostridium tetani) can kill an adult human. Exotoxin. proteins have two polypeptide components (Figure 3) ; one is responsible for binding to the host cell, and one is responsible for the toxic effect. Diphtheria toxin (produced by Corynebacterum diphtheria) is an enzyme that blocks protein synthesis. Most exotoxins are inactivated by heating (60 C), heat labile toxin (LT), Staphylococcal enterotoxin and E. coli are heat-stable toxin (ST). 3
Treatment with dilute formaldehyde destroys the toxic activity of most exotoxins but not their antigenicity. Formaldehyde-inactivated toxins, called toxoids, are useful in preparing vaccines. Exotoxin proteins are encoded by genes carried on plasmids or temperate bacteriophages. An example is the diphtheria exotoxin is encoded by the Tox gene of a bacteriophage. Strains of C. diphtheriae that carry this phage are pathogenic, whereas those that lack the phage are nonpathogenic. b. Endotoxins: are lipopolysaccharides, are not secreted, but are integral components in the outer membranes of the cell walls of G- bacteria released into the host's circulation following bacterial cell lysis, are heat-stable, find in of G- but not G+ bacteria, caused severe septic shock syndrome. The outer membranes consist of LPS: - Polysaccharide O (somatic antigen), which its from the exterior cell surface. - lipid A that faces the cell interior, responsible for the toxicity of this molecule. The main physiologic effects of LPS endotoxins are fever, shock, hypotension, and thrombosis, called as septic shock. These effects are produced indirectly by activation of macrophages,complement and coagulation cascade, with the release of cytokines. Death can result from multiple organ failure. In G+ bacteria their cell wall, peptidoglycan, can cause a shock syndrome similar to that caused by LPS, but usually not as severe. Because the peptidoglycan fragments of G+ bacteria are chemically so different from LPS, and are also less potent. B. Antigenic switching A successful pathogen must evade the host's immune system (that recognizes bacterial surface antigens) change its surface antigens by several mechanisms: 1- Phase Variation, is the ability of certain bacteria to turn off and turn on the expression of genes coding for surface antigens. 2- Antigenic Variation, is the modification of the gene for an expressed surface antigen, by genetic recombination with one of many variable unexpressed DNA sequences, so the expressed surface antigen can assume many different antigenic structures. 4
C. Which is the pathogen? If a particular microorganism is isolated from infected tissue, the organism could be a harmless member of the normal skin flora or an opportunistic pathogen (is an organism that is unable to cause disease in healthy, but cause disease in immunocompromised individuals ). A nineteenth century German microbiologist, Robert Koch, recognized this dilemma, and defined a series of criteria (Koch's postulates) by which the identity of the causative microbial agent of a disease can be confirmed (Figure 4) (this protocol fails if the causative organism cannot be cultured in vitro). D. Infections in human populations Bacterial diseases may be : - communicable from person to person (For example, cholera caused by Vibrio cholerae is easily spread) - noncommunicable not from person to person (For example botulism is caused by Clostridium botulinum because only those people who ingest the botulinum exotoxin are affected). Highly communicable diseases, such as cholera, are said to be contagious, and tend to occur as localized epidemics in which the disease frequency is higher than normal. When an epidemic becomes worldwide, it is called a pandemic, such as the 1918 influenza because the human population has never been exposed to, and, thus, has no immunity against, the specific strain of influenza virus. 5