Yuri Anthony D. Sucgang BMLS-2A Types of Symbiotic Associations 1. Mutualism. Both members of the association benefit.

For humans, one classic mutualistic association is that of the the lactic acid bacteria that live on the vaginal epithelium of a woman. The bacteria are provided habitat with a constant temperature and supply of nutrients (glycogen) in exchange for the production of lactic acid, which protects the vagina from colonization and disease. e.g Lactobacilli 2. Commensalism. There is no apparent benefit or harm to either member of the association. e.g Entamoeba coli- is a nonpathogenic species of Entamoeba (protozoan) that frequently exists as a commensal parasite in the human gastrointestinal tract. it is considered harmless. However 3. Parasitism. In biology, the term parasite refers to an organism that grows, feeds and is sheltered on or in a different organism while contributing nothing to the survival of its host. In microbiology, the mode of existence of a parasite implies that the parasite is capable of causing damage to the host. This type of a symbiotic association draws our attention because a parasite may become pathogenic if the damage to the host results in disease. Some parasitic bacteria live as normal flora of humans while waiting for an opportunity to cause disease. Bacterial Pathogenesis A pathogen is a microorganism (or virus) that is able to produce disease. Pathogenicity is the ability of a microorganism to cause disease in another organism, namely the host for the pathogen. As implied above, pathogenicity may be a manifestation of a host-parasite interaction.

In humans, some of the normal bacterial flora (e.g. Staphylococcus aureus,Streptococcus pneumoniae, Haemophilus influenzae) are potential pathogens that live in a commensal or parasitic relationship without producing disease. They do not cause disease in their host unless they have an opportunity brought on by some compromise or weakness in the host's anatomical barriers, tissue resistance or immunity. Opportunistic Pathogens Bacteria which cause a disease in a compromised host which typically would not occur in a healthy (noncompromised) host are acting as opportunistic pathogens. e.g Staphylococcus aureus or E. coli can cause an opportunistic infection, but so can an environmental organism such as Pseudomonas aeruginosa- one of the most common opportunistic pathogens of humans. The bacterium causes urinary tract infections, respiratory system infections, dermatitis, soft tissue infections, bacteremia and a variety of systemic infections, particularly in cancer and AIDS patients who are immunosuppressed. Infection The normal flora, as well as any "contaminating" bacteria from the environment, are all found on the body surfaces of the animal; the blood and internal tissues are sterile. If a bacterium, whether or not a component of the normal flora, breaches one of these surfaces, an infection is said to have occurred. Infection does not necessarily lead to infectious disease. Some bacteria rarely cause disease if they do infect; some bacteria will usually cause disease if they infect. But other factors, such as the route of entry, the number of infectious bacteria, and (most importantly) the status of the

host defenses, play a role in determining the outcome of infection.

Determinants of Virulence Pathogenic bacteria are able to produce disease because they possess certain structural or biochemical or genetic t raits that render them pathogenic or virulent. (The term virulence is best interpreted as referring to the degree of pathogenicity.) Properties of the Host The host in a host-parasite interaction is the animal that maintains the parasite. The bacterial parasite has its determinants of virulence that allow it to invade and damage the host and to resist the defenses of the host. The host has various degrees of resistance to the parasite in the form of the host defenses. Host Defenses A healthy animal can defend itself against pathogens at different stages in the infectious disease process. The host defenses may be of such a degree that infection can be prevented entirely. Or, if infection does occur, the defenses may stop the process before disease is apparent. At other times, the defenses that are necessary to defeat a pathogen may not be effective until infectious disease is well into progress. Host defense mechanisms are divided into two groups: Innate Defenses. The innate defenses have also been referred to as "natural" or "consitutive" resistance, since they are inherent to the host. Inducible Defenses. Defense mechanisms that must be induced or turned on by host exposure to a pathogen (as during an infection). Synonymous with acquired or adaptive immunity The Immune System

The termimmune usually means the ability to resist infectious disease. Immunity refers to the relative state of resistance of the host to a specific pathogen brought on by the activities of the immunological system. Acquired or Adaptive Immunity, itself, is sometimes divided into two types, based on how it is acquired by the host. In active immunity, the host undergoes an immunological response and produces the cells and factors responsible for the immunity, i.e., the host produce its own antibodies and/or immuno-reactive lymphocytes. Active immunity can persist a long time in the host, up to many years in humans. In passive immunity there is acquisition by a host of immune factors which were produced in another animal, i.e., the host receives antibodies and/or immunoreactive lymphocytes originally produced in another animal. Passive immunity is typically short-lived and usually persists only a few weeks or months. Antimicrobial Agents One line of defense against bacterial infection is chemotherapy with antimicrobial agents such as antibiotics. The ecological relationships between animals and bacteria in the modern world are mediated by the omnipresence of antibiotics. Antibiotics are defined as substances produced by a microorganism that kill or inhibit other microorganisms. Originally, a group of soil bacteria, the Streptomyces, were the most innovative producers of antibiotics for clinical usage. They were the source of streptomycin, tetracycline, erythromycin and chloramphenicol, to name just a few antibiotics. Because bacteria evolve rapidly toward resistance, because bacteria

can exchange genes for antibiotic resistance, and because we have overused and misused antibiotics, many pathogens are emerging as resistant to antibiotics. There have already been reported infections by Enterococcus, Staphylococcus aureus and Pseudomonas aeruginosa that are refractory to all known antibiotics. Bacterial resistance to antimicrobial agents has become part of a pathogen's determinants of virulence. These are examples of genetic means by which bacteria exert their virulence. The body heals itself: most antibiotics just stop bacterial growth, and the host must rely entirely on its native defenses to accomplish the neutralization of bacterial toxins or the elimination of bacterial cells. The judicious use of antibiotics in the past five decades has saved millions of lives from infections caused by bacteria. Mechanisms of Bacterial Pathogenicity Introduction A pathogen is a microorganism that is able to cause disease in a plant, animal or insect. Pathogenicity is the ability to produce disease in a host organism. Microbes express their pathogenicity by means of their virulence, a term which refers to the degree of pathogenicity of the microbe. Hence, the determinants of virulence of a pathogen are any of its genetic or biochemical or structural features that enable it to produce disease in a host. The Underlying Mechanisms of Bacterial Pathogenicity Two broad qualities of pathogenic bacteria underlie the means by which they cause disease: 1. Invasiveness is the ability to invade tissues. It encompasses mechanisms for colonization (adherence and initial multiplication), production of extracellular substances which

facilitate invasion (invasins) and ability to bypass or overcome host defense mechanisms. 2. Toxigenesis is the ability to produce toxins. Bacteria may produce two types of toxins called exotoxins and endotoxins. Exo toxins are released from bacterial cells and may act at tissue sites removed from the site of bacterial growth. Endotoxins are cell-associated substance. (In a classic sense, the term endotoxin refers to the lipopolysaccharide component of the outer membrane of Gram-negative bacteria). However, endotoxins may be released from growing bacterial cells and cells that are lysed as a result of effective host defense (e.g. lysozyme) or the activities of certain antibiotics (e.g. penicillins and cephalosporins). Hence, bacterial toxins, both soluble and cell-associated, may be transported by blood and lymph and cause cytotoxic effects at tissue sites remote from the original point of invasion or growth. Some bacterial toxins may also act at the site of colonization and play a role in invasion.

VIRULENCE FACTORS
COLONIZATION The first stage of microbial infection is colonization: the establishment of the pathogen at the appropriate portal of entry. Pathogens usually colonize host tissues that are in contact with the external environment. Sites of entry in human hosts include the urogenital tract, the digestive tract, the respiratory tract and the conjunctiva. Bacterial Adherence to Mucosal Surfaces. In its simplest form, bacterial adherence or attachment to a eucaryotic cell or tissue surface requires the participation of two factors:

TABLE 3. SOME EXTRACELLULAR BACTERIAL PROTEINS THAT ARE CONSIDERED INVASINS

Invasin

r e Hyaluronidase c e Collagenase p t o Neuraminidase r

Coagulase a Kinases d

Bacteria Involved Streptococci, staphylococci and clostridia Clostridiumspecies Vibrio choleraeand Shigella dysenteriae Staphylococcus aureus Staphylococci and streptococci Staphylococcus aureus

Activity Degrades hyaluronic of connective tissue Dissolves collagen framework of muscles Degrades neuraminic acid of intestinal mucosa Converts fibrinogen to fibrin which causes clotting Converts plasminogen to plasmin which digests fibrin Disrupts neutrophil membranes and causes discharge of lysosomal granules Repels phagocytes and disrupts phagocyte membrane and causes discharge of lysosomal granules Phospholipases or lecithinases that destroy red blood cells (and other cells) by lysis Destroy lecithin in cell membranes Destroy phospholipids in cell membrane

a Leukocidin n
Streptolysin l

Streptococcus pyogenes Streptococci, staphylococci and clostridia Clostridium perfringens Clostridium perfringens

i g Hemolysins a n Lecithinases d . Phospholipases

The receptors so far defined are usually specific carbohydrate or peptide residues on the eucaryotic cell surface. The bacterial ligand, called an adhesin, is typically a macromolecular component of the bacterial cell surface which interacts with the host cell receptor. INVASION The invasion of a host by a pathogen may be aided by the production of bacterial extracellular substances which act against the host by breaking down primary or secondary defenses of the body. Medical microbiologists have long referred to these substances as invasins. Most invasins are proteins (enzymes) that act locally to damage host cells and/or have the immediate effect of facilitating the growth and spread of the pathogen. The damage to the host as a result of this invasive activity may become part of the pathology of an infectious disease.

negative bacteria, and proteins, which are released from bacterial cells and may act at tissue sites removed from the site of bacterial growth. The cellassociated toxins are referred to as endotoxinsand the extracellular diffusible toxins are referred to as exotoxins. Endotoxins are cell-associated substances that are structural components of bacteria. Most endotoxins are located in the cell envelope. In the context of this article, endotoxin refers specifically to the lipopolysaccharide (LPS) or lipooligosaccharide (LOS) located in the outer membrane of Gram-negative bacteria. Although structural components of cells, soluble endotoxins may be released from growing bacteria or from cells that are lysed as a result of effective host defense mechanisms or by the activities of certain antibiotics. Endotoxins generally act in the vicinity of bacterial growth or presence. Exotoxins are usually secreted by bacteria and act at a site removed from bacterial growth. However, in some cases, exotoxins are only released by lysis of the bacterial cell. Exotoxins are usually proteins, minimally polypeptides, that act enzymatically or through direct action with host cells and stimulate a variety of host responses. Most exotoxins act at tissue sites remote from the original point of bacterial invasion or growth. However, some bacterial exotoxins act at the site of pathogen colonization and may play a role in invasion.

EVASION OF HOST DEFENSES Most successful pathogens, however, possess additional structural or biochemical features which allow them to resist the main lines of host internal defense against them, i.e., the phagocytic and immune responses of the host. Bacterial Toxigenesis Toxigenesis, or the ability to produce toxins, is an underlying mechanism by which many bacterial pathogens produce disease. At a chemical level, there are two main types of bacterial toxins, lipopolysaccharides, which are associated with the cell wall of Gram-

Spread of Infection A source of infecting microorganism or other infectious agent in a reservoir in sufficient numbers to cause infection. A susceptible host; and A path for transmission (exit, transmission route and place of entry) to the susceptible host. CONTACT TRANSMISSION DROPLET TRANSMISSION AIRBORNE TRANSMISSION COMMON VEHICLE TRANSMISSION (Fomites)- microorganisms transmitted by contaminated items such as food, water, medications, devices and equipment. These items are referred to as fomites. VECTOR-BORNE TRANSMISSION