Study Notes on Microbial Pathogenicity

Let us make an in-depth study of microbial pathogenicity. The below given article will help you to learn about the sources and spread of infection in community.

Pathogenicity is the ability of the microbes to initiate the infection. It requires three attributes:

1. Transmissibility or communicability from one host or reservoir to a fresh host;

2. Infectivity or the ability to breach the new host’s defences;

3. Virulence, a variable factor that may enhance or reduce the capacity of the pathogen to cause overt infection.

Pathogens (Pathogenic microorganisms) cause diseases and they may be:

(a) Opportunistic, or

(b) True pathogens.

Opportunistic Pathogens:

Many commensal or non-pathogenic microorganisms may be transmissible from person to person or derived from the environment and are present, in large numbers, on the skin, in the upper respiratory tract, in the intestine and lower urinogenital tract hence they are normal micro flora of the body and sometimes they may act against invading pathogenic microorganisms and are unable to invade the tissues as they cannot overcome the healthy body defences.

Sometimes, when the body defence mechanism is lowered and when these commensals leave their natural habitat and reach other parts of the body, e.g., coliform bacilli (Escherichia coli) are mostly harmless commensals in the intestine, but they may cause infection in the urinary tract; similarly Clostridium welchii, an intestinal commensal, can cause gangrene in locally damaged tissues; Streptococcus viridians is the commensal of the mouth; after tooth extraction they may invade the blood stream and settle on previously damaged heart valves as opportunistic pathogens.

True Pathogens:

They are those microorganisms which are able to overcome the normal body defence mechanism and initiate the infection.

Several properties are essential for pathogenicity of microorganisms:

(a) Transmissibility:

The ability of a pathogen to grow profusely in the body and to be shed in large numbers in body fluids or secretions which are capable of dissemination and reach new host after surviving in the adverse conditions, e.g., desiccation in the dry dust.

(b) Infectivity:

Pathogenic microbes are able to initiate the infection by penetrating the healthy body’s first line of defence, that is, skin, mucous membranes to which they readily gain access. To infect a person, only a few of the pathogens can cross the protective barriers in the respiratory and alimentary tracts. The pathogen may initiate a localised lesion at the site of infection, e.g., staphylococcal boil on the skin or streptococcal pharyngitis in the throat.

The capacity of the microbes to initiate the infection is mostly related to the dosage of the pathogen, its phase of growth and its virulence factors. In salmonella family, the infecting dose of Salmonella typhi is very small; whereas large number of S. typhimurium (food poisoning salmonellae) must be ingested to produce acute vomiting and diarrhoea.

Microorganisms which are in the logarithmic stage of growth are more likely to overcome host resistance than those in the latent phase: Streptococcus pyogenes is more infective when transferred directly from a person with a sore throat than when it is inhaled after drying in dust particles, because Strepto pyogenes has the capsular M protein (anti-phagocytic component) during the active phase of sore throat infection.

(c) Virulence:

The virulence of a pathogen is the ability to kill susceptible animals (mouse, guinea pig etc.). The tubercle bacillus isolated from Indian patients with tuberculosis are often less virulent to the guinea pigs than strains isolated in Britain. The assessment of virulence for animal is not necessarily applicable to virulence of man.

Shigella dysenteries causes much more severe infection than Sh.sonnei. Similarly, the gravis strain of Corynebacterium diphtheriae causes more deaths than the misstrain. Type 1 poliovirus is more likely to initiate epidemics of paralytic poliomyelitis than is type 2.

Pathogenesis:

Pathogenic bacteria produce diseases by virtue of one or both of the main attributes: Toxigenecity and invasiveness.

Toxigenecity:

Toxins may be (a) exotoxins or (b) endotoxins,

(a) Exotoxins:

German and French workers were first to prove that the products of the diphtheria bacilli, diffused from the local infection or injected as bacteria- free filtrates of cultured diphtheria bacilli, could produce widespread systemic damage in guinea pigs. The toxin produced by diphtheria bacilli in the throat is carried by the blood stream (toxaemia) throughout the body.

When the bacteria grow actively in broth culture, they secrete apparently the poison which is called as “exotoxin” Other bacteria which secrete highly potent toxins are tetanus bacilli and Clostridium botulinum. So 1.0 mg. of tetanus and botulinal toxin can kill more than one million guinea pigs and it is estimated that 3 kg of botulinal toxin can kill the world population.

Exotoxins are mainly produced by gram-positive bacilli (except Shigella bacillus neurotoxin and cholera enterotoxin) and have special affinity for specific tissues; for example, tetanus, botulinal and diphtheria toxins all affect different parts of the nervous system: tetanus toxin affects control mechanisms that govern motor cells in the anterior columns of the spinal cord; botulinal toxin paralyses cranial nerves by blocking the transmission of effector messages from their endings; and diphtheria toxin has affinity for peripheral nerve ending as well as for specialised tissues like heart muscle.

Exotoxins behave like enzymes: alpha toxin of CI. welchii is a phospholipase (lecithinase C) which acts on phospholipids of cell membrane; diphtheria toxins depress the formation and/or release of acetylcholine in different parts of the nervous system.

(b) Endotoxins:

They are complex phospholipid polysaccharide – protein macromolecules. Most of the endotoxins are lipopolysaccharides and additional endotoxin released by few gram-negative pathogenic bacteria (Yersinia pestisand Bordetella pertussis) is protein in nature and is present in the bacterial cytoplasm. They are released only after natural autolysis or artificial disruption of bacterial cells and therefore they are called endotoxins.

Typical endotoxins are particularly associated with gram-negative bacteria (salmonella, shigella, Escherichia, Neisseria) and are distinguishable from exotoxins by the following properties:

1. They are present in the outer layer of the bacterial cell wall;

2. They are heat stable;

3. They are much less toxic and specific in their cytotoxic effects than exotoxins;

4. They cannot be converted into toxoids;

5 Homologous antibodies cannot render them non-toxic, if combined.

The complex phospholipid-polysaccharide- protein molecule can be separated by phenol extraction into:

(a) Lipopolysaccharide moiety,

(b) Protein fraction,

(c) Phospholipid fraction.

The lipopolysaccharide moiety can be split further into different sugars including those that determine the antigenic specificity of the endotoxin and lipid which is mainly responsible for the toxicity. Pyrogenic effect (fever) is the toxic effect produced by the smallest amount of endotoxin. If 0.002 μ g endotoxin per kg body weight is injected intravenously into rabbit or man, it causes within 15 minutes an elevation of body temperature which lasts for several hours.

Invasiveness:

It is the other main attribute of pathogenic bacteria. It is its capacity to invade and multiply in the healthy tissues, e.g., pneumococcus produces the disease depending entirely upon the quality of invasiveness just as botulinus bacillus depends entirely on its toxigenicity. Thus, the diphtheria bacillus must be initially invasive in order to establish itself in the tissues of the oropharynx, where it manufactures its toxin; the gravis strain of diphtheria bacillus has the greater capacity to invade and multiply in the tissues with a consequent greater production of toxin than mitis strain. Strepto. pyogenes is mainly an invasive pathogen.

It also produces an erythrogenic toxin which is responsible for the rash of the scarlet fever. The invasiveness of Staph, aureus, Strepto. pyogenes and CI. welchii is due to their production of cytolytic and leucocidal toxins which enable them to breach tissue barriers and protect themselves against phagocytosis.

Pathogenic bacteria which are predominantly invasive are:

1. The First Category—:

The pathogenic gram positive cocci initially attract phagocytes by chemotactic mechanisms, resist phagocytosis; but ultimately they may be engulfed and destroyed by phagocytes.

2. The Second Category —:

Tubercle bacilli, typhoid, brucella bacilli, though they are readily phagocytosed are more resistant to destruction when within phagocytes and become intracellular parasites which are disseminated by phagocytes throughout the body.

There is fight between phagocytes and anti-phagocytic bacteria; when specific antibody acting as opsonins come to the aid of the phagocytes in destroying the anti-phagocytic bacteria, then these bacteria are destroyed by phagocytes and there is a dramatic fall in temperature — the crisis — as observed in pneumococcal pneumonia. In infection with intracellular parasites there is clinical illness that persists for some weeks with low fever.

Capsules and Pathogenicity:

The bacterial capsule plays an important role in conferring the virulence on bacteria by enabling them to resist phagocytosis and bactericidal substances in body fluids, therefore the capsulation is important for the virulence of pneumococci, streptococci of Group A and Group C, the anthrax bacillus, the plague bacillus, Kbesiella pneumonia and Haemophilus influenza.

It has been observed that the non-capsulate bacteria are rapidly phagocytosed and, within a few hours, are mostly destroyed, whereas the capsulate bacteria remain free and soon multiply to large numbers. The mechanism of the anti-phagocytic property of capsulate bacteria is not known, but it may be that the lipid containing cell membrane of the phagocyte’s pseudopodia is inhibited from making contact with the hydrated capsule gel because of the surface charge. However, heavily capsulate harmless saprophytic bacteria and some non-virulent strains of bacillus anthracis and plague bacilli are fairly susceptible to phagocytosis.

Aggressins —:

Other non-toxic protective or aggressive factors that may contribute to the ability of capsulate and non-capsulate pathogens to invade and multiply in the host tissues are:

1. Hyaluronidase or spreading factor, is an enzyme that dissolves the hyaluronic acid or cement like substances that binds cells together and so allows pathogens (Strepto. pyogenes, Staph, aureus) to permeate through the tissues.

2. Coagulase Prothrombin —:

Like enzyme produced by all pathogenic staphylococci may help to protect the pathogen from phagocytosis into two ways:

(a) by forming fibrin barriers around staphylococci and staphylococcal lesions, and

(b) by inactivating the bactericidal substance present in the normal blood serum.

3. Streptokinase Secreted by Strepto:

Pyogenes may promote the spreading of streptococcal lesions.

4. Collagenase, produced by CI. welchii, may play some part in the pathogenesis of gas gangrene.

5. Neuraminidase produced by some bacteria and viruses acts on mucoproteins of cell surface and may facilitate attacks on the cell.

Organotropism:

The affinity of many pathogenic microbes for specific tissues or organs is known as organotropism. Pneumococcus and meningococcus both have the natural habitat in the nasopharynx, but the virulent pneumococcus has a predilection for lung tissues and the meningococcus for the meninges of the brain, whereas gonococcus mainly affects the mucosa of urethra.

Brucella abortus localizes in the uterus of cows because of the presence of erythritol, a growth factor for Br.abortus, in the bovine placenta. However, Coxiella burnetti and chlamydiae localise in the uterus but they do not use erythritol.