Pathogenicity Islands: Properties and Types

 Pathogenicity islands (PAIs) are large groups of mobile genetic elements that are associated with pathogenicity and are located on the bacterial chromosome. These genetic elements are thought to have evolved from lysogenic bacteriophages and plasmids and are transferred by horizontal gene transfer. The concept of PAI was founded in the late 1980s by Jörg Hacker and colleagues.

PAIs are typically comprised of one or more virulence-associated genes and “mobility” genes (i.e., integrases and transposases) that mediate movements between various genetic elements (e.g., plasmids, and chromosomes) and among different bacterial strains.

The presence of pathogenicity islands (PAIs) in the genomes of bacterial pathogens is one of the main features that differentiate them from closely related nonpathogenic strains or species.

The major properties of PAIs are as follows:

1. Pathogenicity islands have one or more virulence genes
2. PAIs are large organized groups of genes, usually 100 to 200 kb in size.
3. They are present in parts of the genome associated with mobile genetic elements and cause genetic instability
4. These islands typically have different guanine plus cytosine content than the rest of the bacterial genome. 

Types of Pathogenicity Islands

Pathogenicity islands (PAIs) are genetic elements in bacterial genomes that play a significant role in the virulence of the bacteria. These islands often carry genes involved in pathogenicity, allowing the bacteria to cause disease in their host organisms. There are several pathogenicity islands, each associated with specific functions or mechanisms. Some common types include Type I to VI and metabolic pathogenicity islands. 

The classification of pathogenicity islands is only sometimes clear-cut, and some islands may exhibit characteristics of multiple types. Additionally, ongoing research may reveal new types or variations in pathogenicity islands.

Type I Pathogenicity Islands

Type I pathogenicity islands are genetic elements present in the genomes of certain pathogenic bacteria. They typically play a crucial role in the virulence and pathogenicity of these bacteria. The presence of genes that contribute to the ability of the bacteria to adhere to and invade host cells.

1. Adhesion and Invasion Genes: Type I pathogenicity islands often harbor genes involved in adhesion to host cells and subsequent invasion. Adhesion is the initial step in establishing an infection. This allows the bacteria to attach to specific receptors on the surface of host cells.
2. Locus of Enterocyte Effacement (LEE): The LEE is a well-known Type I pathogenicity island in specific pathogenic Escherichia coli (E. coli) strains, including enteropathogenic E coli (EPEC) and enterohemorrhagic E coli (EHEC). The LEE contains a gene cluster that encodes a type III secretion system (T3SS) and effector proteins. These proteins help in the formation of attaching and effacing (A/E) lesions on the surface of host cells.
3. Functions of LEE: The LEE facilitates the injection of effector proteins into host cells. This leads to cytoskeletal rearrangements, pedestal formation, and intimate attachment of the bacteria to the host cell surface. This intimate attachment is a critical step in the pathogenesis of diseases caused by EPEC and EHEC, such as diarrhea and hemolytic uremic syndrome (HUS).
4. Role in Disease: Type I pathogenicity islands, including the LEE, contribute significantly to the ability of these bacteria to colonize the host, evade the host immune system, and cause disease.

Type II Pathogenicity Islands

Type II pathogenicity islands are genetic elements present in the genomes of certain bacteria. These contribute to their virulence and ability to cause disease. These islands features a type II secretion system (T2SS), a complex machinery responsible for the secretion of various virulence factors, including enzymes and toxins, into the extracellular environment. Here are some key features and examples of Type II pathogenicity islands:

1. Type II Secretion System (T2SS): The genes encoding a type II secretion system (T2SS) is a characteristic feature of these island. The T2SS is a protein secretion apparatus that spans Gram-negative bacteria’s inner and outer membranes. It facilitates the transport of virulence factors from the bacterial periplasm into the extracellular environment.
2. Secretion of Virulence Factors: The T2SS secretes various proteins, including enzymes and toxins, contributing to the bacterium’s virulence. The T2SS produces proteins like proteases, lipases, and toxins that can damage host tissues or interfere with the host’s immune response.
3. Pseudomonas aeruginosa: This bacteria is a well-known pathogenic bacterium with a Type II secretion system. The T2SS in P. aeruginosa aids in the secretion of several virulence factors, including exotoxin A, elastase, and phospholipases, which contribute to the bacterium’s pathogenicity.
4. Role in Disease: The proteins secreted by the T2SS can play a crucial role in establishing and progressing bacterial infections. They may contribute to tissue damage, evasion of the host immune response, and nutrient acquisition.
5. Target Host Cells: Type II secretion systems target a wide range of host cells and tissues, allowing the bacteria to adapt to different environments within the host organism.

Type III Pathogenicity Islands

These are genetic elements present in the genomes of certain bacteria. A type III secretion system (T3SS) is a characteristic feature of of these islands. These islands play a crucial role in the virulence and pathogenicity of the bacteria by injecting effector proteins into the host cells. The T3SS is a needle-like structure that allows bacteria to deliver specific proteins into the eukaryotic host cells.

1. Type III Secretion System (T3SS): The T3SS is a complex molecular machinery that spans Gram-negative bacteria’s inner and outer membranes. It forms a needle-like structure that extends from the bacterial surface. It allows the direct injection of effector proteins into the host cell.
2. Effector Proteins: Type III pathogenicity islands carry genes encoding effector proteins injected into the host cell cytoplasm through the T3SS. These effector proteins manipulate various cellular processes, such as the cytoskeleton, signaling pathways, and immune responses, to create a favorable bacterial survival and replication environment.
3. Salmonella Pathogenicity Islands (SPI): Salmonella enterica, a bacterial pathogen responsible for causing diseases like salmonellosis, possesses multiple Type III pathogenicity islands known as Salmonella Pathogenicity Islands (SPI). SPI-1 and SPI-2 are most popular examples of Type III pathogenicity islands in Salmonella. SPI-1 is involved in the invasion of epithelial cells, while SPI-2 is associated with macrophage survival.
4. Enteropathogenic Escherichia coli (EPEC): It is another example of a bacterium with a Type III secretion system. It uses its T3SS to inject effector proteins into host cells. The injection leads to attaching and effacing lesions on the cell surface.
5. Role in Disease: The T3SS and associated effector proteins are critical for the bacteria’s ability to establish infections, evade the host immune system, and cause diseases.The injection of effectors allows bacteria to modulate host cell functions to their advantage, promoting colonization and survival.

Type IV Pathogenicity Islands

These are genetic elements present in the genomes of certain bacteria. The T4SS is a versatile secretion machinery that can transfer DNA and proteins between bacterial cells and between bacteria and eukaryotic host cells.

1. Type IV Secretion System (T4SS): Genes encoding a type IV secretion system (T4SS) characterizes the Type IV pathogenicity islands. The T4SS is a complex molecular apparatus that spans the bacterial cell envelope.
2. DNA Transfer: T4SSs can transfer DNA between bacterial cells, promoting horizontal gene transfer. This process can contribute to the spread of virulence genes, antibiotic resistance genes, and other traits among bacterial populations.
3. Virulence Factor Delivery: Type IV pathogenicity islands often encode virulence factors that can be delivered to eukaryotic host cells. These factors may include toxins, effectors, or proteins that manipulate host cell functions.
4. Agrobacterium tumefaciens Ti Plasmid: One of the best-studied examples of this type is the Ti plasmid present in Agrobacterium tumefaciens. A. tumefaciens uses its T4SS to transfer a segment of DNA (T-DNA) from the Ti plasmid to plant cells. This leads to the development of crown gall tumors.
5. Legionella pneumophila: Legionella pneumophila, which causes Legionnaires’ disease, possesses a Type IV secretion system called the Dot/Icm system. The Dot/Icm system helps in the survival and replication of L. pneumophila inside the host cells.
6. Helicobacter pylori cag Pathogenicity Island: Helicobacter pylori can cause stomach ulcers and gastric cancer. It has a pathogenicity island known as the cag (cytotoxin-associated genes). The cag island encodes a Type IV secretion system that delivers the CagA effector protein into host cells.
7. Role in Disease: The T4SS and associated pathogenicity islands are crucial in bacteria’s ability to colonize host tissues, evade immune responses, and cause disease. The transfer of genetic material through T4SS can enhance the adaptability and virulence of bacterial populations.

Type V Pathogenicity Islands

Type V pathogenicity islands are genetic elements present in the genomes of certain bacteria, usually associated with autotransporter proteins. Autotransporters are a protein secretion system that allows bacteria to transport and deliver various virulence factors to their surroundings.

1. Type V Secretion System (Autotransporter System): The genes encoding autotransporter proteins is characteristic feature of this type. The autotransporter which are a secreted virulence factor. Autotransporters are famous for their ability to transport and secrete themselves across the bacterial outer membrane.
2. Autotransporter Structure: Autotransporters typically consist of three functional domains. These are a signal sequence, a passenger domain (carrying the effector function), and a translocation domain. The signal sequence guides the autotransporter to the bacterial periplasm. Similarly, the translocation domain transports the passenger domain across the outer membrane.
3. Adhesion and Toxin Delivery: Autotransporters often play a role in adhesion to host cells and tissues, contributing to the initiation of infection. Some autotransporters also function as toxins or deliver toxins to host cells, contributing to the pathogenicity of the bacteria.
4. Examples of Autotransporters: The diffuse adherence island (DAI) in uropathogenic Escherichia coli (UPEC) is an example of a Type V pathogenicity island. The DAI encodes autotransporters contributing to UPEC’s adherence to urinary tract epithelial cells. The pertactin autotransporter in Bordetella pertussis aids in adhesion to respiratory epithelial cells and have regard as a virulence factor in whooping cough.
5. Role in Disease: Type V pathogenicity islands, through autotransporter proteins, play a role in establishing and progressing bacterial infections by mediating adhesion to host cells and facilitating the delivery of virulence factors. These islands contribute to the bacteria’s ability to colonize specific niches within the host and evade immune responses.

Type VI Pathogenicity Islands

Type VI pathogenicity islands (T6SS) are genetic elements present in the genomes of certain bacteria. The Type VI secretion system is a complex protein apparatus delivering toxic effector proteins directly into eukaryotic host cells and bacterial competitors. Here are key features and examples of Type VI pathogenicity islands:

1. Type VI Secretion System (T6SS): The genes encoding a type VI secretion system (T6SS) characterizes these pathogenicity islands. The T6SS is a molecular weapon bacteria use to inject toxic effector proteins into target cells.
2. Contractile Structure: The T6SS consists of a contractile sheath-like structure resembling a bacteriophage tail, allowing the injection of effector proteins into adjacent cells.
3. Effector Proteins: T6SS delivers effector proteins directly into eukaryotic host cells and competing bacterial cells. These effector proteins can have diverse functions, disrupting cell membranes, interfering with cell division, or inhibiting competitor bacterial growth.
4. Interbacterial Competition: T6SS is often helpful in interbacterial competition, allowing bacteria to eliminate or inhibit the growth of neighboring bacteria by injecting toxic effectors.
5. Role in Pathogenesis: T6SS has been implicated in the virulence of various pathogenic bacteria, contributing to their ability to colonize host tissues, evade the immune system, and establish infections.
6. Examples of Bacteria with T6SS:
   • Vibrio cholerae: The bacterium responsible for cholera possesses a T6SS involved in bacterial competition and contributes to its pathogenicity.
   • Burkholderia pseudomallei: The bacterium Burkholderia pseudomallei, causing melioidosis, utilizes T6SS for survival and competition within host cells.
7. Regulation and Expression: The expression of the T6SS is often tightly regulated, and environmental cues, host signals, or the presence of competing bacteria influence its activation.
8. Environmental Adaptation: T6SS may help bacteria adapt to different environmental niches and contribute to their fitness in complex microbial communities.

Metabolic Pathogenicity Islands

These are genetic elements in the genomes of certain bacteria that play a role in the metabolic adaptation of the bacteria during infection. Unlike other pathogenicity islands that primarily encode virulence factors, MPIs carry genes involved in metabolic pathways that allow the bacteria to utilize specific nutrients within the host environment. These islands contribute to the bacteria’s ability to establish infections and adapt to the host’s metabolic conditions.

1. Metabolic Adaptation: MPIs are helpful in the metabolic adaptation of bacteria to the host environment. They carry genes that enable the utilization of specific nutrients available in the host tissues.
2. Nutrient Acquisition: These islands often encode proteins involved in acquiring and utilizing nutrients, such as sugars, amino acids, or other metabolites present in the host.
3. Regulation of Metabolism: MPIs may contain regulatory elements that control the expression of metabolic genes, allowing bacteria to fine-tune their metabolic activities based on the host environment.
4. Examples of Metabolic Pathogenicity Islands:
   • Escherichia coli O157:H7: This pathogenic strain of E. coli has been reported to contain metabolic pathogenicity islands that utilize specific carbon sources during infection.
   • Listeria monocytogenes: Listeria is known for its ability to survive and multiply in various host environments. It possesses genomic islands involved in sugar metabolism and nutrient acquisition, contributing to its pathogenicity.
   • Streptococcus pneumoniae: Some strains of S. pneumoniae carry metabolic islands involved in carbohydrate metabolism, facilitating their adaptation to different host niches.
5. Role in Virulence: While MPIs are primarily associated with metabolic adaptation, they indirectly contribute to virulence by enhancing the fitness of the bacteria within the host. By efficiently utilizing available nutrients, bacteria can persist, replicate, and establish infections more effectively.
6. Host-Pathogen Interactions: MPIs reflect the dynamic interactions between the host and the pathogen at the metabolic level, highlighting the importance of nutrient availability and utilization during infection.

Examples of Pathogenicity Islands

Few examples of the very large number of pathogenicity islands of human pathogens are:

Genus/Species	PAI Name	Virulence Characteristics
Escherichia  coli	PAI I536	Alpha hemolysin, fimbriae, adhesions, in urinary tract infections.
Escherichia coli	PAI Ij96	Alpha hemolysin, P-pilus in urinary tract infections
Escherichia coli (EHEC)	01#7	Macrophage toxin of enterohaemorrhagic Escherichia coli
Salmonella typhimurium	SPI-1	Invasion and damage of host cells, diarrhea
Yersinia pestis	HPI/pgm	Gene that enhance iron uptake
Vibrio cholerae EL tor O1	VPI-1	Neuraminidase, utilization of amino sugars
Staphylococcus aureus	SCC mec	Methicillin and other antibiotic resistance
Staphylococcus aureus	SaPI1	Toxic shock syndrome toxin-1, enterotoxin
Enterococcus faecalis	NPm	Cytolysin, biofilm formation

 

References

1. Schmidt, H., & Hensel, M. (2004). Pathogenicity islands in bacterial pathogenesis. Clinical microbiology reviews, 17(1), 14–56. https://doi.org/10.1128/CMR.17.1.14-56.2004
2. Arias, C. A., & Murray, B. E. (2015). Enterococcus species, streptococcus gallolyticus group, and Leuconostoc species. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. https://doi.org/10.1016/b978-1-4557-4801-3.00202-2