Microbiology Final

influenza A - primary pathogen that has a capsid with a lipoprotein envelope acquired from host cells after reproducing in the cell and leaving the cell. this capsid is where the N and H spike proteins are. the most virulent and serious strain of influenza virus. has an H/hemagglutinin surface protein that allows the virus to bind to sialic acid on cell surfaces to enter into the cell and replicate. birds have sialic acid in the cells of their respiratory and intestinal tracts, while humans have sialic acid in their respiratory tract cells. sialic acid is the receptor of the H protein. sialic acid is found in most body cells of warm blooded animals, but in great amounts on the lung cells. this virus has 8 segments of single stranded rna for its genetic material. Hemagglutinin spikes bind to red blood cells and cause them to stick together- agglutination. Neuraminidase spike proteins help the virions escape the host cell during budding.

influenza chain of infection - inhalation of respiratory droplets from humans, birds, or pigs, or fomites infected with virions that enter the mucus membranes in the eyes, nose, mouth. bird feces can also spread the flu. the virus then attaches to respiratory epithelial cells via the H protein.

influenza A reservoirs- humans, birds, pigs. especially aquatic birds

flu-like symptoms - come from the inflammatory response to infections = fever, body aches, chills, fatigue

tamiflu - inhibiting neuraminidase proteins so that virions cannot escape the host cell and spread the infection further in the body

• Primary Pathogen: Influenza A is a serious strain with a lipoprotein envelope and 8 segments of single-stranded RNA.

• Capsid Proteins: Contains hemagglutinin (H) and neuraminidase (N) spike proteins.

• Hemagglutinin (H) Protein: Allows the virus to bind to sialic acid on cell surfaces to enter and replicate. Birds have sialic acid in their respiratory and intestinal cells, while humans have it in respiratory tract cells.

• Neuraminidase (N) Protein: Helps virions escape the host cell during budding.

• Agglutination: Hemagglutinin spikes cause red blood cells to stick together.

influenza exhibits antigenic drift/variation that allows for mutations of H and N proteins spikes, that make the virus unrecognizable to the immune system. specific versions of the H and N proteins determine the subtype of the flu virus. this is mostly due to the fact influenza A can make its own RNA polymerase that copies its genome- but they are extremely error prone- leading to mutations

influenza A exhibits antigenic shift - swapping of genetic material between subtypes of influenza virus. the 8 segment RNA can mix in the host’s cell and a new virus can be created and can jump to new species. this happens in pigs most often, where a pig is infected with human influenza and a bird influenza at the same time.

Staphylcoccus aureus - dairy based foods and creamy salads. Growth Conditions: Staphylococcus aureus is a facultative anaerobe, meaning it can grow in both oxygen-rich and oxygen-poor environments. It multiplies rapidly at temperatures between 40°F to 140°F (4°C to 60°C), known as the 'danger zone' for food safety. It can also tolerate high salt concentrations and pH levels, which allows it to survive in many types of food. Toxin Production: This organism produces an enterotoxin that is responsible for food poisoning. Even if the bacteria are killed through cooking, the toxins they produced prior to cooking can remain in the food and lead to illness.

Aspergillus - grains and nuts. Aspergillus is a genus of fungi commonly found in various grains (such as wheat, barley, and corn), nuts (like peanuts), and dried fruits. It often thrives in warm, humid conditions, making these food items particularly susceptible to contamination. Mycotoxin Production: The most notable mycotoxin produced by Aspergillus species is aflatoxin, which is highly toxic and carcinogenic. Aflatoxins can contaminate crops before harvest or during storage, especially in inadequate conditions.

Bacillus cereus - grains and vegetables. Growth Conditions: Bacillus cereus is a resilient bacterium that can survive cooking temperatures due to its ability to form spores. Once food is improperly cooled and then reheated, these spores can germinate and produce toxins.

Clostridium perfringens - meats and gravies. Clostridium perfringens is an anaerobic bacterium, which means it thrives in environments with little or no oxygen. It can produce spores that survive cooking temperatures. When cooked food is left out at unsafe temperatures (not kept

C. diff - opportunistic pathogen, gram positive bacillus, forms endospores, obligate anaerobe. C. diff produces two exotoxins. Toxin A and Toxin B are both type 3 toxins that must enter the cell to cause their effect. They deactivate proteins that regulate intracellular signals. Results in two effects - cytopathic effects change the shape and connections of intestinal cells, and cytotoxic effects that damage and kill intestinal cells. primarily effects the colon and prevented water absorption leading to lots of diarrhea. c.diff grows VERY slowly, and it can be destroyed by a healthy immune system.

• Pseudomembrane Formation:These toxins bind to receptors on the surface of colon cells, leading to cell death and inflammation. the damage results in the formation of a pseudomembrane, which is a layer of inflammatory cells, mucus, and cellular debris

The severity of a Clostridium difficile (C. diff) infection can be influenced by several factors, including:

1. Age: Older adults, particularly those over 65 years, are at higher risk for severe cases of C. diff due to a generally weaker immune system.

2. Underlying Health Conditions: Individuals with chronic illnesses (such as diabetes, kidney disease, or inflammatory bowel disease) may have compromised immunity, making them more susceptible to severe infections.

3. Antibiotic Use: The recent use of antibiotics can disrupt the normal gut flora, allowing C. diff to thrive. The type and duration of antibiotic therapy can influence severity, with certain antibiotics (like clindamycin and fluoroquinolones) posing higher risks.

4. Treatment History: Individuals who have had prior C. diff infections are at increased risk for recurrent or severe infections. Previous treatment courses may contribute to antibiotic resistance or further disturbance of gut flora.

5. Virulence Strain: Some strains of C. diff produce more toxins or are more resistant to treatment. For example, the NAP1 strain is associated with more severe diseases and higher recurrence rates.

6. Immunosuppression: Patients undergoing chemotherapy, organ transplants, or those on long-term corticosteroid therapy have weakened immune responses, making them more vulnerable to severe infections.

7. Environmental Factors: Presence of spores in healthcare settings can increase exposure risk. Poor hygiene and sanitation practices can facilitate the spread of C. diff and contribute to more severe outbreaks.

8. Previous C-diff exposure: Having a previous C. diff infection can cause a person to become a carrier of C. diff spores which will reinfect the person Reinfection Trigger: Under circumstances like antibiotic use, changes in diet, or stress, the gut flora can be disrupted in a carrier, allowing dormant spores to germinate and multiply.

9. Germination: Upon ingestion or re-exposure to suitable conditions (e.g., nutrient-rich environments in the gut), the spores can germinate back into vegetative bacteria, leading to a new infection.This cycle perpetuates the risk of recurrent Clostridioides difficile infections, making it crucial to manage and monitor carriers effectively.

   Pneumonia - inflammation of the air sacs/alveoli of the lungs. inflammation causes a fluid or mucus buildup in the lungs and can lead to symptoms like coughing, difficult breathing, chest pain, and shortness of breath.

   H. flu pneumonia - gram negative bacteria. Hemophilus influenzae type B/Hib causes the most serious form of the disease. Has a capsule, which helps it to adhere to the respiratory tract and avoid phagocytosis. has fimbriea to adhere tightly to the respiratory tract. it is an opportunistic infection. causes inflammation by releasing LPS, causing inflammation that damages lung cells and leaks fluid into alveoli. also increases mucus production. H flu can’t survive outside the host for more than a few hours.

   S. pneumoniae - streptococcus pneumoniae - a gram-positive bacterium that is a common cause of pneumonia, characterized by its polysaccharide capsule. uses pneumolysin to escape phagocytosis. pneumolysin is a type 2 toxin that opens holes in the cell membranes of neutrophils and macrophages, and damages cells of the alveoli leading to inflammation and pneumonia. it is a primary pathogen due to its exotoxin pneumolysin.

   
   both H flu and S pneumoniae have subunit vaccines, but cannot provide full immunity because both have high degree of antigenic variation. must be boosted frequently.

   host factors for bacterial pneumonia - age and immune status, inhaling particles that are irritating to the lungs, recent respiratory infections, diabetes, COPD, difficult swallowing increases risk of aspirating bacteria into the lungs, long term use of ventilator increases autoinoculation risk, frequent vomiting or GERD can carry microbes from nose and throat to lungs. these combined with pneumonia can lead to serious complications - acute respiratory distress/impaired gas exchange, sepsis, intensified cardiovascular disease.

viral pneumonia - caused by SARS COV2 and RSV/respiratory syncytial virus.

RSV - an enveloped virus with an RNA genome. spike protein for attachment is the G protein that binds to ciliated cells in the respiratory tract. Capsid shape varies. causes cytopathic effects- killing ciliated cells and causes inflammation, so mucus accumulates. can cause bronchiolitis, closing the bronchioles and preventing gas exchange. can cause a wheezing sound as the airway narrows, dry cough, respiratory distress. RSV is spread person to person, and can live outside the body for up to 2 weeks. primary pathogen. ID50 is less than 50 virions. there are no antivirals against RSV.

COVID - primary pathogen RNA virus with geometric capsule, enveloped and has spike proteins. it rapidly mutates. S proteins bind to ACE 2 receptors, which is found numerously in the lungs, blood vessels, heart. Causes a cytopathic effect as it enters the cell and a powerful inflammation response that destroys healthy tissues. initial waves of virion replication occur in the olfactory and upper respiratory cells - resulting in anosmia

sepsis - overwhelming, body wide inflammatory response when normally sterile tissues are infected. causes an innate immune hyperreaction. organ dysfunction caused by a dysregulated immune response to an infection or toxin , can be viral, bacterial, fungal, or parasitic. usually is a result of systemic infection but can result from localized infections as well. technically microbes do not need to enter the bloodstream or lymph vessels for sepsis to develop.

early sepsis symptoms - shivering, extreme pain, pale skin, sleepiness, impending doom, shortness of breath

lethal triad - a positive feedback loop that causes sepsis. begins with inflammation caused by an invasive infection, which triggers blood clotting in the body called coagulopathy, which blocks blood flow and causes cardiovascular instability- causing more inflammation and coagulopathy.

cardiovascular instability - coagulopathy causes blocks and damage to blood vessels, which manifests as a blotchy purple to black sepsis rash. the damage causes more inflammation.

as blood is lost to clotting, it causes persistent low blood pressure that can’t be treated.

massive inflammation during sepsis causes changes that cause apoptosis of B and T cells.

most sepsis patients die from immunosuppression that makes them unable to fight off pathogens, and 10% die due to organ damage and failure

septicemia - sepsis triggered by a pathogen or toxin spreading through the blood

septic shock - hypotension - blood pressure drops and blood is not properly circulated to organs and tissues - causing necrosis and organ failure

disseminated intravascular coagulation - formation of blood clots throughout the body leads to organ failure and necrosis

escherichia coli, staphylococcus aureus, and streptococcus are most common sepsis inducing agents

lung and kidney infections have the highest risk of spreading to the bloodstream and inducing sepsis

managing sepsis - focus on reducing inflammation, regulating body temp, stabilizing blood pressure and increasing blood oxygen.

hepatitis - pathological condition of liver inflammation, can be infectious or noninfectious. infectious hepatitis is primarily caused by hepatitis A,B,C,D,E viruses’

acute phase hepatitis - lasts less than 6 months, and the infection is cleared by the immune system and results in a full recovery. almost all cases are asymptomatic, but may cause nausea/vomiting, fatigue, fever, loss of appetite, jaundice. less than 1% develop an immune hyperreaction called fluminant hepatitis that results in autoimmune attack on the liver and leads to liver failure\

chronic phase hepatitis - lasts more than 6 months, and becomes a chronic persistent infection that the immune system can’t clear where the virus genome is inserted into host cells.

HAV - primary pathogen naked RNA virus, which makes it more resistent to disinfectants. causes acute phase hepatitis only. enters via ingestion through the mouth, infects the cells of the digestive tract and destroys them- allowing the virus to enter the blood and then the liver as the liver filters the blood. viruses leave the body through bile produced by the liver and exit through the feces. takes 2-3 weeks for symptoms to manifest if they do, so outbreaks are common and associated with food prep.

HBV - enveloped with double strand DNA, can cause acute or chronic hepatitis but is easily disinfected because of the envelope, enter the body via blood and sexual secretions via broken skin/mucuous membranes. replication in the liver causes acute phase hepatitis which is mostly asymptomatic. infected people can become carriers where there is no immune response, or they will experience a chronic infection. in the chronic phase, the immune system can’t clear the infection- so the virus goes dormant but causes flares of symptoms that damage the liver. can lead to cirrhosis and liver cancer.

HCV - enveloped with an RNA genome, can cause acute or chronic hepatitis but is easily disinfected because of the envelope. chronic phase HCV establishes a non cytopathic chronic persistent infection. doesn’t kill the liver cells but can trigger immune response against the liver cells - can also cause cirrhosis and liver cancer.

DIGESTIVE INFECTIONS

gastroenteritis is inflammation of the stomach and intestines caused by microbial infections

enterotoxin - an exotoxin that targets intestinal cells, enters the GI usually after bacteria grow on food that is eaten and covered with enterotoxin. food poisoning symptoms begin within a few hours of exposure, and last for 12-48 hours. cannot be passed to another person

gastrointestinal infections typically take 2-4 days for symptoms to appear, and can be passed from person to person

HPV - primary pathogen double strand DNA virus, naked so it is highly resistant to disinfection. the spike protein is the capsid L1 protein that binds to the basal layer of stratified epithelial tissues. enters the body through broken or mucus membranes. establishes a latent persistent infection, with an episome in the nucleus of the host cell. the viral genome is replicated during cell division but doesn’t produce viruses. normally mitosis only occurs in the basal layer but the virus causes it to continue after it reaches the surface, causing warts. virus only releases from cells upon normal cell death. there are over 200 types of HPV. most HPV infections are cleared within 2 years by the immune system.

cutaneous HPV - infect stratified epithelium of the skin, causing warts on the hands and feet. warts are overgrowths of skin cells

mucosal HPV - infect stratified epithelium of the mouth, throat, genitals. low risk types cause warts, and high risk types cause cancers

high risk HPV - establishes a chronic persistent infection and the virus DNA is integrated into the basal cell chromosome as a provirus. the viral genes cause the basal cells to lose the ability to regulate mitosis - causing cancer

HIV - primary pathogen, enveloped with spikes made of two proteins, and each one has its own receptor, and requires both for entry. the virus infects T-helper cells because they attach to CD4 receptors. people who do not have CCR5 receptor are immune to HIV. HIV sets up a chronic persistent infection and reverse transcriptase translates its RNA to DNA so it can be inserted into the host genome. HIV integrase permanently inserts the provirus into the T helper cell chromosome.. viral genome is single strand RNA, with an irregular capsid packed with 3 viral enzymes. reverse transcriptase, integrase, and protease. HIV virus leaves the host cell by budding which is how it gets its envelope. after budding HIV protease cuts up the HIV polyproteins the host cell produces to make them useable by the virus and the virus becomes mature and can infect other people

stages of untreated HIV infections

1. acute phase typically lasts about 3 months and the virus sets up the chronic persistent infection. mild flu like symptoms as the immune system fights back, but can’t destroy the provirus inserted into the T helper cells.

2. chronic phase lasts 7-10 years, slow replication and destruction of T helper cells, typically asymptomatic

3. AIDS is acquired immune deficiency syndrome, and now the immune system cannot stop infections or cancers due to the loss of T helper cells

HIV Overview

• Primary Pathogen: Enveloped virus with spikes made of two proteins requiring both receptors (CD4 and CCR5) for entry. Infects T-helper cells.

• Immunity: Individuals lacking the CCR5 receptor are immune to HIV.

• Genetic Integration: HIV uses reverse transcriptase to convert its RNA to DNA and integrase to insert this DNA into the host genome permanently.

• Structure: Single-stranded RNA genome with a capsid containing reverse transcriptase, integrase, and protease.

• Viral Budding: Virus exits the host cell via budding, acquiring its envelope. Protease then processes viral polyproteins to mature the virus.

meningitis - infection of the connective tissue coverings of the brain, when the cerebrospinal fluid, or tissue of meninges gets infected. glial cells of the nervous system surround and seal capillaries in the brain to prevent pathogens from entering. the pathogen breaks down the blood brain barrier to enter the brain. can only be caused by invasive pathogens that spread from their original infection site in the body.

Neisseria meningitidis is the most common cause of meningitis in teenagers and young adults. gram negative coccus that releases LPS upon death. type 4 pilli help it to attach to body tissues, and the capsule allows it to evade the immune system because it is is made of a sugar called polysialic acid, which is found in epithelial cells of blood vessels and mucous membranes in the human body so the immune system doesn’t really react to it. first neisseria must colonize and invade the nasal cavity epithelium with its type 4 pilli. tricks the cells of the nose to open a pathway for invasion to the blood. the second round of colonization and invasion occurs in the epithelium of brain blood vessels, where it tricks the cells to break down the blood brain barrier and invade the meninges. they trick the host cells to break down using a cortical plaque, and they activate receptors that break down proteins that hold epithelium together, giving the bacteria a pathway. when neisseria invades, they release LPS as they are phagocytized or destroyed by innate defenses. when in the blood LPS causes sepsis like symptoms.

symptoms of Neisseria sepsis or meningococemia - pale skin with red or purple spots, fever and body aches, and unusually cold hands or feet. can also cause increased pressure in the cranium, due to inflammed and swelled meninges. this pressure squeezes the brain and blood vessels and causes ischemia.