Pathogenicity 2 Flashcards
explain S layers
Outermost Layer: S-layers are the outermost layer of many bacterial cell envelopes. They form a crystalline, often paracrystalline, structure that covers the bacterial cell.
Self-Assembly: S-layers are composed of protein or glycoprotein subunits that self-assemble into a highly organized, repeating pattern. This self-assembly allows the structure to be precisely formed.
Abundant: S-layers can make up a substantial portion of a bacterial cell’s proteins, accounting for up to 10% of the total cellular protein content.
Rapid Synthesis: In fast-growing bacteria, such as those during exponential growth, up to 500 protein subunits can be added to the S-layer structure every second. This dynamic construction allows the bacterium to rapidly adapt to changing conditions.
Functions:
Protection: S-layers provide a protective coat around the bacterial cell. This protection can shield the bacterium from potentially harmful environmental factors, such as desiccation, chemicals, or host immune responses.
Mechanical Strength: S-layers contribute to the mechanical stability of the bacterial cell envelope, helping it withstand physical stresses.
Molecular Sieve: The regular pattern of S-layers can act as a molecular sieve, allowing only specific molecules to pass through.
Adhesion: S-layers often contain binding sites that allow the bacterium to adhere to surfaces, including host tissues. This adhesion can be crucial for colonization and infection.
Immune Evasion: S-layers can serve as a barrier against host immune defenses, such as antibodies and complement proteins, making it more difficult for the host to recognize and eliminate the bacterium.
Immune Suppression: In some cases, S-layers have been associated with modulating the host’s immune responses, potentially dampening inflammation and aiding in bacterial survival.
explain bacterial vesicles
Production by Gram-Negative Bacteria: Bacterial vesicles are primarily produced by Gram-negative bacteria. These vesicles are often derived from the bacterial outer membrane and are released into the extracellular environment.
Appearance in Transmission Electron Microscopy (TEM): Bacterial vesicles can be observed under a transmission electron microscope (TEM). They appear as small, spherical structures, often seen as surface blebs on the bacterial cell membrane.
Functions of Bacterial Vesicles:
Haemagglutinin Function: Bacterial vesicles can carry various molecules on their surfaces, including proteins. Some vesicles have been shown to have haemagglutinin function. Haemagglutinins are proteins that can bind to red blood cells (erythrocytes), causing them to agglutinate or clump together.
Sialidase (Neuraminidase) Activity: Sialidases, also known as neuraminidases, are enzymes that cleave sialic acid residues from glycoproteins and glycolipids. Some bacterial vesicles can carry sialidase activity, which can modify or degrade sialic acid-containing molecules.
Transport of Endotoxins: Bacterial vesicles can transport endotoxins, which are lipopolysaccharides (LPS) found in the outer membrane of Gram-negative bacteria. These vesicles can deliver endotoxins to target cells, potentially triggering inflammatory responses.
Role in Intercellular Communication: Bacterial vesicles are increasingly recognized for their role in intercellular communication. They can carry various signaling molecules, including proteins, lipids, and genetic material. These vesicles can transfer information between bacteria or between bacteria and host cells.
Implications in Pathogenicity: Bacterial vesicles are associated with the pathogenicity of some bacteria. They can deliver virulence factors, toxins, and other molecules to host cells, contributing to infection and disease.
Potential as Therapeutic Targets: Because of their involvement in bacterial pathogenicity, bacterial vesicles are considered potential therapeutic targets in the development of treatments for bacterial infections.
explain anthrax
Anthrax is a bacterial disease caused by the bacterium Bacillus anthracis. Here are some key points about Bacillus anthracis and its pathogenic features:
Bacterial Agent: Bacillus anthracis is a Gram-positive, rod-shaped bacterium known for its role in causing anthrax, a potentially dangerous infectious disease.
Biological Weapon: Bacillus anthracis is of concern as a potential biological weapon. The spores of multiply antibiotic-resistant strains of this bacterium can be produced and dispersed in the air, posing a significant public health threat.
Anti-Phagocytic Capsule: One of the key pathogenic features of Bacillus anthracis is its ability to evade the host’s immune defenses. It does so by synthesizing an outer glycoprotein covering made from poly-D-glutamic acid (PGDA). This capsule acts as an anti-phagocytic structure, making it difficult for white blood cells (WBCs), such as macrophages, to engulf and destroy the bacteria. The capsule is not easily digestible by phagocytic cells.
Peptide Link to DAP: The anti-phagocytic capsule of PGDA is attached to diaminopimelic acid (DAP) on some of the N-acetylmuramic acid (NAM) side-chains through a peptide link. This attachment enhances the resistance of Bacillus anthracis to phagocytosis by host immune cells.
Teichoic and Lipoteichoic Acids: Bacillus anthracis also produces teichoic and lipoteichoic acids, which are components of the bacterial cell wall. These components can provide some level of resistance to phagocytosis and contribute to the bacterium’s ability to evade the host’s immune system.
Inhalational Anthrax: Inhalational anthrax is the most severe form of the disease and is often associated with exposure to airborne spores. Once inhaled, the spores can germinate in the lungs and lead to systemic infection.
Vaccine and Antibiotics: Vaccination and prompt treatment with antibiotics, such as ciprofloxacin or doxycycline, are important measures for preventing and treating anthrax. These interventions are particularly crucial in cases of potential exposure to anthrax spores.
explain the colonization of mucosal membranes by pathogenic microorganisms
Resistance to Lysozyme: Lysozyme is an antimicrobial enzyme found in various bodily secretions, including tears, saliva, and mucus. It acts by breaking down peptidoglycan, a component of bacterial cell walls. Pathogenic microorganisms have developed mechanisms to resist or evade lysozyme’s action. This resistance may involve the production of protective structures, such as capsules or biofilms, that shield the bacteria from the enzymatic activity of lysozyme.
The Battle for Iron: Iron is an essential nutrient for both humans and bacteria. However, iron is often limited in the human body as it is mostly bound to proteins like hemoglobin. Pathogenic bacteria have evolved various strategies to acquire iron from the host. This includes the secretion of siderophores—small molecules that can scavenge iron and bring it back to the bacteria. Bacterial competition for iron with the host’s iron-binding proteins is a significant aspect of colonization and infection.
Attachment: Attachment is a crucial step in the colonization of mucosal surfaces. Bacterial adhesins, which are surface structures or proteins, play a role in binding to host cells and tissues. This binding is often specific, allowing the bacteria to target particular host receptors. Adhesins can be located on the bacterial surface or on extracellular appendages like pili or fimbriae. Attachment is an important initial step before bacteria can establish infection.
Additionally, biofilm formation, which involves the aggregation of bacterial cells and the secretion of extracellular polymeric substances, is another mechanism that enhances colonization on mucosal surfaces. Biofilms provide a protective environment for bacteria and allow them to resist host defenses and antibiotics.
The ability of pathogenic bacteria to colonize mucosal surfaces and resist host defenses is a critical aspect of the establishment of infections.
explain the lysozyme
Lysozyme, an enzyme found in various bodily secretions like tears, saliva, and mucus, is primarily effective against Gram-positive bacteria. It functions by breaking down the peptidoglycan layer, a component of bacterial cell walls, causing bacterial lysis.
However, some pathogenic Gram-positive bacteria have developed mechanisms to resist or evade lysozyme’s activity. In the case of Staphylococcus aureus, a well-known Gram-positive coccus bacterium, it has developed resistance through the O-acetylation of peptidoglycan. This process involves the addition of an acetyl group to the C6 -OH group of N-acetylmuramic acid (NAM), a component of peptidoglycan.
The enzyme responsible for this acetylation process in S. aureus is known as O-acetyltransferase A (OatA). This modification of peptidoglycan makes the bacterium less susceptible to lysozyme action and contributes to its ability to colonize and cause infections in humans. S. aureus is a significant human pathogen and can cause a range of infections, from skin and soft tissue infections to more severe conditions like bacteremia and endocarditis.
explain how iron is a critical component of several important molecules and proteins
Cytochromes of the Electron Transport Chain (ETC): Iron is a key component of cytochromes, which play a crucial role in electron transport and oxidative phosphorylation, the processes by which cells generate energy.
Enzyme Cofactor: Iron serves as a cofactor for many enzymes, participating in various enzymatic reactions essential for cellular functions.
Hemoglobin: Iron is a central component of hemoglobin, the protein in red blood cells responsible for binding and transporting oxygen throughout the body. Hemoglobin gives blood its red color.
Transferrin is a protein that plays a vital role in transporting iron in the bloodstream. It binds to iron ions, preventing them from freely circulating and causing damage to tissues. Transferrin helps maintain iron in a soluble, non-toxic form.
Lactoferrin is another iron-binding protein found in various bodily secretions, including human milk, saliva, tears, nasal secretions, and vaginal secretions. Lactoferrin acts as a secondary defense mechanism against microbial pathogens by sequestering iron. When iron is bound to lactoferrin, it becomes less available for microorganisms to utilize for their growth and survival.
Lactoferrin secretion can increase during infections or inflammatory responses, reflecting the body’s attempt to limit iron availability to invading microorganisms. By restricting iron access to pathogens, the host can hinder their growth and, in some cases, improve the chances of eliminating the infection.
explain siderophores
In the human body, free iron concentrations are maintained at extremely low levels, typically in the range of 10^-18 to 10^-24 M. These levels are insufficient to support the growth and survival of most bacterial pathogens, which require iron for their metabolic processes and virulence. Therefore, bacteria have developed various mechanisms to scavenge iron from the host’s iron-binding proteins and carriers. One such mechanism involves the production and secretion of siderophores.
Siderophores are small, high-affinity iron-chelating molecules that are secreted by bacteria into their surrounding environment. These molecules have a strong affinity for iron and can capture iron ions even at extremely low concentrations. Once secreted, siderophores act as “iron magnets,” binding to any available iron ions and forming siderophore-iron complexes.
Bacteria can then recover these siderophore-iron complexes and import them into the cell using specific transport systems. Inside the bacterial cell, iron is released from the siderophore, making it available for the bacterium’s metabolic processes.
Siderophores play a critical role in bacterial iron acquisition and are essential for the growth and virulence of many pathogenic bacteria. By producing siderophores, bacteria effectively scavenge the limited iron resources available in the host’s tissues, allowing them to overcome the host’s iron-sequestration strategies and thrive in the iron-deficient environments of the human body. In addition to siderophores, some bacteria, like Staphylococcus aureus (S. aureus), secrete hemolysins. Hemolysins are toxins that can damage or lyse red blood cells (erythrocytes), releasing hemoglobin. Hemoglobin contains iron, and hemolysins allow bacteria to strip iron from hemoglobin, further enhancing their ability to obtain this essential nutrient. This strategy helps bacteria like S. aureus acquire iron in the host’s bloodstream, where hemoglobin is abundant.
suggest how these molecules bind Fe3+ with such high affinity
Siderophores bind Fe³⁺ (ferric iron) with high affinity through several key structural and chemical features:
Hydroxamate or catecholate groups: Siderophores typically contain functional groups, such as hydroxamate (-N(O)OH) or catecholate (-O-C6H4-O-) moieties, which are highly effective at coordinating with iron ions. These functional groups can form multiple strong coordination bonds with ferric iron, allowing siderophores to capture iron ions effectively.
High ligand concentration: Siderophores often contain multiple binding sites for iron ions, enabling them to bind several iron atoms simultaneously. This high ligand concentration contributes to the overall affinity of siderophores for iron.
Chelation effect: The multiple binding sites provided by the hydroxamate or catecholate groups create a chelation effect. Chelation occurs when multiple donor atoms from the siderophore surround a central metal ion, forming a stable and highly coordinated complex.
Molecular complementarity: The structure of siderophores is specifically designed to match the size, charge, and coordination preferences of iron ions. This molecular complementarity ensures a strong and selective binding between siderophores and ferric iron.
Acid-base chemistry: The hydroxamate and catecholate functional groups of siderophores have acidic hydroxyl (OH) groups that can donate electrons to coordinate with iron. Iron ions, in turn, can accept these electrons, forming coordinate bonds that are relatively stable.
The combination of these factors allows siderophores to outcompete other molecules in their environment, effectively capturing ferric iron even at very low iron concentrations. The resulting siderophore-iron complexes can then be transported into the bacterial cell, where the iron is released and used for various metabolic processes, including energy production and other functions essential for the bacterium’s growth and survival.
explain siderocalin
Siderocalin, also known as lipocalin-2 (Lcn2), is an innate immune protein produced by various host cells, including epithelial cells and neutrophils. It plays a crucial role in the host’s defense against bacterial pathogens by sequestering siderophores. Siderophores are small molecules secreted by bacteria to scavenge iron, which is essential for their growth and survival.
Siderocalin has a unique calyx-shaped binding pocket that can capture siderophores and tightly bind to them. This binding effectively neutralizes the iron-scavenging ability of siderophores, preventing bacteria from acquiring the iron they need to proliferate and evade host defenses.
During infection, the host produces siderocalin and secretes it into various bodily fluids, such as serum and urine, as a defense mechanism against invading bacteria. This is a part of the innate immune system’s strategy to limit the availability of free iron, a critical nutrient for many bacterial pathogens.
explain hepcidin
It is produced primarily by the liver in response to various stimuli, including infection and inflammation. Hepcidin plays a critical role in controlling the levels of iron in the blood.
During infection and inflammation, the body’s immune response is activated. As a part of this response, hepcidin production increases. Hepcidin functions to reduce the concentration of iron in the plasma by inhibiting the absorption of dietary iron in the intestines and promoting the sequestration of iron in macrophages, particularly in the liver and spleen.
The reduction in plasma iron levels caused by hepcidin has several effects:
Decreased availability of iron for bacteria, limiting their access to this essential nutrient.
Iron sequestration in macrophages, preventing its release into the bloodstream.
Induction of hypoferremia, which can lead to anemia in cases of prolonged or severe inflammation.
Hepcidin’s role in regulating iron levels is a protective mechanism that helps to limit the availability of iron to invading pathogens during infections. However, excessive or prolonged production of hepcidin can lead to disorders of iron metabolism and contribute to the development of anemia associated with chronic inflammatory conditions.
explain borrelia burgdorferi
Borrelia burgdorferi, the bacterium responsible for Lyme disease, has developed some unique strategies for coping with its host’s defenses and living within the host.
Iron-Free Genome: As you mentioned, B. burgdorferi has an iron-free genome. It has replaced iron in its enzymes with magnesium. This adaptation helps it avoid competing with the host for limited iron resources. Iron is essential for many biological processes, but it is often tightly regulated by the host to limit its availability to pathogens. B. burgdorferi’s reliance on magnesium instead of iron for its enzymes allows it to evade this competition for iron and carry out essential metabolic processes.
Spirochaete Morphology: B. burgdorferi has a unique spiral or spirochaete shape, which enables it to move through tissues, including those of its host, efficiently. This corkscrew-like morphology allows it to penetrate tissues and evade the host’s immune defenses.
Stealth and Immune Evasion: B. burgdorferi has various mechanisms to evade the host’s immune system, including antigenic variation. It frequently changes the surface proteins it expresses, making it difficult for the host’s immune system to recognize and target the bacterium effectively.
Host Adaptation: B. burgdorferi can exist in multiple forms, including spirochetal, round body, and biofilm-like structures. This adaptability allows it to persist in diverse host environments and avoid immune detection.
explain spirochaetes
Spirochaetes are a unique group of bacteria characterized by their spiral or corkscrew-like shape and their distinct motility mechanisms, which involve endoflagella. These endoflagella play a crucial role in the spirochaetes’ corkscrew-like motion. Here’s a closer look at their motility:
Endoflagella: Spirochaetes possess specialized flagella called endoflagella. These flagella are located within the periplasmic space (between the inner and outer membranes) of the spirochaete cells. The endoflagella are not exposed on the cell’s surface like typical external flagella but are enclosed within the cell’s envelope.
Axial Filament: The endoflagella are arranged as a pair of long, coiled filaments that run along the length of the spirochaete cells, typically within the periplasmic space. This structure is referred to as the axial filament.
Rotation and Corkscrew Motion: The endoflagella generate a characteristic corkscrew motion. When they rotate, one endoflagellum will rotate in one direction (e.g., clockwise), while the other rotates in the opposite direction (e.g., counterclockwise). This rotation generates a twisting or corkscrew-like movement of the entire spirochaete cell.
Propulsion: The corkscrew-like motion generated by the endoflagella allows spirochaetes to propel themselves through viscous environments, such as host tissues. This unique motility mechanism helps spirochaetes move efficiently within their host organisms and is critical for their pathogenicity.
High Rotational Speed: The endoflagella can rotate at very high speeds, often exceeding 100,000 revolutions per minute (rpm), which contributes to the rapid motion of spirochaetes.
This distinctive corkscrew-like motility enables spirochaetes to move through complex environments, evade host defenses, and establish infections.
which Spirochaete causes syphilis? suggest a specific advantage of endoflagella to infection
Syphilis is caused by the spirochaete bacterium Treponema pallidum. Treponema pallidum is known for its distinctive spiral shape and endoflagella-driven motility.
Advantages of Endoflagella to Infection:
Tissue Penetration: Spirochaetes with endoflagella, like Treponema pallidum, can efficiently penetrate various tissues in the host organism. The corkscrew-like motion generated by the endoflagella allows them to navigate through dense tissues, including those of the skin, mucous membranes, and blood vessels.
Evading Immune Responses: The unique motility conferred by endoflagella helps spirochaetes evade the host’s immune responses. The rapid and unpredictable corkscrew motion makes it challenging for the host’s immune cells to track and phagocytose these bacteria effectively.
Establishing Infections: Spirochaetes use their endoflagella to reach and invade specific tissues where they can establish infections. In the case of Treponema pallidum, this enables the bacterium to infiltrate mucous membranes or enter the bloodstream, facilitating its dissemination within the host.
Colonization: Spirochaetes with endoflagella can colonize host tissues, such as the genital mucosa in the case of syphilis, allowing them to establish chronic infections and potentially transmit the disease to other hosts.
Host Tropism: The motility provided by endoflagella can be crucial for spirochaetes to reach their preferred colonization sites, demonstrating a level of host tropism. This tropism is advantageous for the bacterium in terms of colonization and infection.
explain how typhoid fever is a potentially life-threatening illness caused by the bacterium Salmonella enterica serotype Typhi, a gram-negative bacterium
Typhoid fever is a potentially life-threatening illness caused by the bacterium Salmonella enterica serotype Typhi, a gram-negative bacterium. It is transmitted through the consumption of contaminated food or water. Salmonella Typhi is highly adapted to the human host and is primarily a human pathogen.
Key Features of Salmonella enterica serotype Typhi:
Gram-Negative Rod: Salmonella Typhi, like other bacteria in the Enterobacteriaceae family, has a gram-negative cell wall structure. This includes an outer membrane, which contains lipopolysaccharides (LPS) and serves as an important component in its pathogenesis.
Flagella: Salmonella Typhi is motile, possessing 6 to 10 flagella. These flagella enable the bacterium to move, aiding in its ability to penetrate host tissues and establish infection. Flagellin, the protein that makes up the flagella, can show antigenic variation.
Antigenic Phase Variation: Antigenic phase variation is a phenomenon where pathogens alter their surface antigens to evade the host’s immune response. In the case of Salmonella Typhi, this allows the bacterium to vary its surface antigens, making it more challenging for the host’s immune system to recognize and combat the infection effectively.
Transmission: Typhoid fever is transmitted primarily through the ingestion of food or water contaminated with the feces of infected individuals. This transmission occurs when individuals consume food or beverages contaminated with Salmonella Typhi.
Symptoms: Typhoid fever is characterized by symptoms such as high fever, gastrointestinal distress, abdominal pain, and in severe cases, can lead to life-threatening complications. The bacterium can invade the bloodstream and various organs.
Vaccine: There are vaccines available to prevent typhoid fever. These vaccines are especially important for travelers visiting regions where typhoid fever is endemic.
Salmonella Typhi has adapted to the human host and causes a systemic infection known as typhoid fever. This pathogen’s ability to vary its surface antigens and its capacity for motility are essential factors in its pathogenicity and the clinical presentation of the disease.
explain how immunoglobulin A (IgA) plays a crucial role in mucosal immunity
Secreted Onto Mucosal Surfaces: IgA is the primary immunoglobulin found in secretions at mucosal surfaces, such as tears, saliva, mucus, colostrum (the first milk produced by mammals), and sweat. This makes it a crucial component of the body’s defense against pathogens that enter through these routes.
Acquired and Innate Immunity: IgA provides both acquired and innate immunity. It can be part of the acquired immune response, where the body produces specific antibodies against particular pathogens. It also contributes to innate immunity by acting as a physical barrier and preventing pathogen adhesion.
Agglutination of Bacteria: IgA has the ability to clump or agglutinate bacteria together. This aggregation can inhibit the bacteria’s movement and ability to adhere to mucosal surfaces, making it easier for the immune system to remove them.
Blocking Pathogen Adhesion: IgA can block pathogen adhesion by targeting specific microbial adhesins, which are molecules that help pathogens attach to host cells. By binding to these adhesins, IgA interferes with the pathogen’s ability to attach to and invade host cells.
Neutralizing Toxins and Enzymes: IgA can neutralize bacterial toxins and enzymes. By binding to these toxic molecules, IgA can prevent them from causing harm to host tissues and cells.
Neutralizing Siderophores: Siderophores are molecules produced by bacteria to scavenge iron from the host. IgA can neutralize these siderophores, limiting the ability of bacteria to acquire iron from the host’s tissues.
