The virulence of a pathogen is affected by a number of different characteristics. A major determinant of virulence is the pathogen's possession of a virulence factor, a feature enabling a pathogen to cause disease by releasing toxins, invading host cells and tissues, suppressing the host's immune responses, or otherwise damaging the host. Virulence factors can be endotoxins, working inside the cell itself, exotoxins, preventing protein synthesis and cell membrane functioning, or exoenzymes, which degrade host tissues.
Some strains of many bacterial pathogens have surface appendages, called pili (or pilus for singular), which they use to attach to hosts. Similarly, some produce surface proteins called adhesins that aid in attachment to host tissues or invasion of host tissues for some pathogens. Whether using pili or adhesins, the pathogen benefits from attaching to a hospitable location where it can reproduce, furthering infection.
Many pathogens produce toxins of various types that are directly harmful to a host. Toxins produced and secreted by bacteria are called exotoxins, and they tend to cause harm to specific target tissues. For example, a type of exotoxin called an enterotoxin affects intestinal tissues, causing diarrhea in the process. Other types of exotoxins include cytotoxins (toxic to cells; may lyse cells releasing their contents for the pathogen to scavenge as food) and neurotoxins (poisonous to nerve tissues). Botulism is a disease caused by the bacterium Clostridium botulinum and has been known to cause flaccid paralysis. It works by preventing the release of the neurotransmitter acetylcholine from the start of the synapse between nerve cells. In contrast, an outer cell membrane component of gram-negative bacteria, lipopolysaccharide, is an endotoxin that results in systemic effects such as fever, inflammation, fluctuating blood pressure, and shock.
Another type of virulence factor helps the pathogen evade or damage the host immune system. Antiphagocytic factors are used to damage or otherwise avoid detection or destruction by white blood cells. The O antigen and H antigen, components of the bacterial outer cell membrane and also endotoxins, inhibit phagocytosis. This prevents the pathogen from being engulfed by macrophages, specialized leukocytes (white blood cells). The Vi capsule antigen inhibits complement binding, a part of the host's innate immune defenses. Certain protease enzymes are released by some bacteria and attack antibody proteins of the host immune system. In all cases, virulence factors aid the pathogen in initial infection, replication, or dispersal.Microbial Virulence Factors
Virulence Factors and Modes of Action
| Virulence Factor | Major Classes | Example | Mechanism of Action |
|---|---|---|---|
| Endotoxin | Not Applicable | Lipopolysaccharide (LPS) on gram-negative bacteria (Pseudomonas aeruginosa) | Triggers immune systemic inflammation |
| Exotoxin | Intracellular targeting - change an active enzymatic component into the cell and modify an intracellular target molecule | Diphtheria toxin (Corynebacterium diphtheriae) | Inhibits host cell protein synthesis; cells die. |
| Membrane disrupting - directly affect membranes, forming pores or disrupting lipid bilayers | Alpha-toxin (Staphylococcus aureus) | Blocks pores of host cell membranes; cells die. | |
| Superantigens - bind surface receptors and stimulate signals across the membrane | No specific examples | None described | |
| Exoenzyme | Glycohydrolases | Staphylococcus aureus | Degrades hyaluronic acid that binds host tissue cells together; this promotes bacteria spread. |
| Nucleases | No specific examples | Degrade polynucleotides, such as DNA and RNA; | |
| Phospholipases | No specific examples | Hydrolizes lipase into fatty acids and glycerol. | |
| Proteases | Clostridium perfringens | Degrades collagen of host connective tissue; this promotes bacteria spread. | |
| Adhesin | Not Applicable | Adhesin F (Streptococcus pyogenes) | Adhere to respiratory epithelial cells. |
| Type IV pili (Neisseria gonorrhoeae) | Adhere to urethral epithelial cells. | ||
| Type 1 fimbriae (enterotoxigenic Escherichia coli) | Adhere to intestinal epithelial cells. | ||
| Capsule | Not Applicable | Streptococcus pneumoniae | Prevents host immune system from adhering and phagocytizing the bacterial cell. |
Microbes have several virulence factors that work to disrupt normal cell functioning. These usually involve creating enzymes that break down cell membranes or binding to surface receptors and causing interruptions to material passage across the cell.