Question

1. List a bacterial pathogen which causes disease by the production of toxins and provide a therapeutic strategy to treat the disease.

2. List a bacterial pathogen which can be directly acquired from an animal (alive or dead), describe the disease and explain why it would be difficult to eradicate the disease.

Answer 1

1.

Resistance to bacterial infections is enhanced by phagocytic cells and an intact immune system. Initial resistance is due to nonspecific mechanisms. Specific immunity develops over time. Susceptibility to some infections is higher in the very young and the very old and in immunosuppressed patients.

Bacterial Infectivity

Bacterial infectivity results from a disturbance in the balance between bacterial virulence and host resistance. The “objective” of bacteria is to multiply rather than to cause disease; it is in the best interest of the bacteria not to kill the host.

Host Resistance

Numerous physical and chemical attributes of the host protect against bacterial infection. These defenses include the antibacterial factors in secretions covering mucosal surfaces and rapid rate of replacement of skin and mucosal epithelial cells. Once the surface of the body is penetrated, bacteria encounter an environment virtually devoid of free iron needed for growth, which requires many of them to scavenge for this essential element. Bacteria invading tissues encounter phagocytic cells that recognize them as foreign, and through a complex signaling mechanism involving interleukins, eicosanoids, and complement, mediate an inflammatory response in which many lymphoid cells participate.

Genetic and Molecular Basis for Virulence

Bacterial virulence factors may be encoded on chromosomal, plasmid, transposon, or temperate bacteriophage DNA; virulence factor genes on transposons or temperate bacteriophage DNA may integrate into the bacterial chromosome.

Host-mediated Pathogenesis

In certain infections (e.g., tuberculosis), tissue damage results from the toxic mediators released by lymphoid cells rather than from bacterial toxins.

Intracellular Growth

Some bacteria (e.g., Rickettsia species) can grow only within eukaryotic cells, whereas others (e.g., Salmonella species) invade cells but do not require them for growth. Most pathogenic bacteria multiply in tissue fluids and not in host cells.

Virulence Factors

Virulence factors help bacteria to (1) invade the host, (2) cause disease, and (3) evade host defenses. The following are types of virulence factors:

Adherence Factors: Many pathogenic bacteria colonize mucosal sites by using pili (fimbriae) to adhere to cells.

Invasion Factors: Surface components that allow the bacterium to invade host cells can be encoded on plasmids, but more often are on the chromosome.

Capsules: Many bacteria are surrounded by capsules that protect them from opsonization and phagocytosis.

Endotoxins: The lipopolysaccharide endotoxins on Gram-negative bacteria cause fever, changes in blood pressure, inflammation, lethal shock, and many other toxic events.

Exotoxins: Exotoxins include several types of protein toxins and enzymes produced and/or secreted from pathogenic bacteria. Major categories include cytotoxins, neurotoxins, and enterotoxins.

Siderophores: Siderophores are iron-binding factors that allow some bacteria to compete with the host for iron, which is bound to hemoglobin, transferrin, and lactoferrin.

Introduction

Infection is the invasion of the host by microorganisms, which then multiply in close association with the host's tissues. Infection is distinguished from disease, a morbid process that does not necessarily involve infection (diabetes, for example, is a disease with no known causative agent). Bacteria can cause a multitude of different infections, ranging in severity from inapparent to fulminating. Table 7-1 lists these types of infections.

Table 7-1

Types of Bacterial Infections.

The capacity of a bacterium to cause disease reflects its relative pathogenicity. On this basis, bacteria can be organized into three major groups. When isolated from a patient, frank or primary pathogens are considered to be probable agents of disease (e.g., when the cause of diarrheal disease is identified by the laboratory isolation of Salmonella spp. from feces). Opportunistic pathogens are those isolated from patients whose host defense mechanisms have been compromised. They may be the agents of disease (e.g., in patients who have been predisposed to urinary tract infections with Escherichia coli by catheterization). Finally, some bacteria, such as Lactobacillus acidophilus, are considered to be nonpathogens, because they rarely or never cause human disease. Their categorization as nonpathogens may change, however, because of the adaptability of bacteria and the detrimental effect of modern radiation therapy, chemotherapy, and immunotherapy on resistance mechanisms. In fact, some bacteria previously considered to be nonpathogens are now known to cause disease. Serratia marcescens, for example, is a common soil bacterium that causes pneumonia, urinary tract infections, and bacteremia in compromised hosts.

Virulence is the measure of the pathogenicity of an organism. The degree of virulence is related directly to the ability of the organism to cause disease despite host resistance mechanisms; it is affected by numerous variables such as the number of infecting bacteria, route of entry into the body, specific and nonspecific host defense mechanisms, and virulence factors of the bacterium. Virulence can be measured experimentally by determining the number of bacteria required to cause animal death, illness, or lesions in a defined period after the bacteria are administered by a designated route. Consequently, calculations of a lethal dose affecting 50 percent of a population of animals (LD50) or an effective dose causing a disease symptom in 50 percent of a population of animals (ED50) are useful in comparing the relative virulence of different bacteria.

Pathogenesis refers both to the mechanism of infection and to the mechanism by which disease develops. The purpose of this chapter is to provide an overview of the many bacterial virulence factors and, where possible, to indicate how they interact with host defense mechanisms and to describe their role in the pathogenesis of disease. It should be understood that the pathogenic mechanisms of many bacterial diseases are poorly understood, while those of others have been probed at the molecular level. The relative importance of an infectious disease to the health of humans and animals does not always coincide with the depth of our understanding of its pathogenesis. This information is best acquired by reading each of the ensuing chapters on specific bacterial diseases, infectious disease texts, and public health bulletins.

Host Susceptibility

Susceptibility to bacterial infections depends on the physiologic and immunologic condition of the host and on the virulence of the bacteria. Before increased amounts of specific antibodies or T cells are formed in response to invading bacterial pathogens, the “nonspecific” mechanisms of host resistance (such as polymorphonuclear neutrophils and macrophage clearance) must defend the host against the microbes. Development of effective specific immunity (such as an antibody response to the bacterium) may require several weeks (Fig. 7-1). The normal bacterial flora of the skin and mucosal surfaces also serves to protect the host against colonization by bacterial pathogens. In most healthy individuals, bacteria from the normal flora that occasionally penetrate the body (e.g., during tooth extraction or routine brushing of teeth) are cleared by the host's cellular and humoral mechanisms. In contrast, individuals with defective immune responses are prone to frequent, recurrent infections with even the least virulent bacteria. The best-known example of such susceptibility is acquired immune deficiency syndrome (AIDS), in which the CD4+ helper lymphocytes are progressively decimated by human immunodeficiency virus (HIV). However, resistance mechanisms can be altered by many other processes. For example, aging often weakens both nonspecific and specific defense systems so that they can no longer effectively combat the challenge of bacteria from the environment. Infants are also especially susceptible to certain pathogens (such as group B streptococci because their immune systems are not yet fully developed and cannot mount a protective immune response to important bacterial antigens. In addition, some individuals have genetic defects of the complement system or cellular defenses (e.g., inability of polymorphonuclear neutrophils to kill bacteria). Finally, a patient may develop granulocytopenia as a result of a predisposing disease, such as cancer, or immunosuppressive chemotherapy for organ transplants or cancer.

Figure 7-1

Serum antibody response to Salmonella typhi during typhoid fever and its relationship to septicemia.

Host resistance can be compromised by