Microbiology Notes - Unit 4 - Chapters 19, 20 and 21

The Respiratory Tract and Its Defenses

Anatomy of the Respiratory System

The respiratory system is divided into two main parts:

  • Upper Respiratory Tract: Includes the mouth, nose, nasal cavity, sinuses, pharynx (throat), epiglottis, and larynx.

  • Lower Respiratory Tract: Begins with the trachea, branching into bronchi and bronchioles within the lungs. Alveoli, small balloon-like structures, are attached to the bronchioles and are the sites of oxygen exchange.

Defenses of the Respiratory System

The respiratory system has several defense mechanisms to protect against infection:

  • Nasal Hair: Traps particles.

  • Cilia: Located on the epithelium of the trachea and bronchi, cilia propel particles upward and out of the respiratory tract (ciliary escalator).

  • Mucus: Traps invading microorganisms.

  • Involuntary Responses: Coughing, sneezing, and swallowing help move trapped microorganisms out of sensitive areas.

  • Second and Third Lines of Defense: Complement action, antimicrobial peptides, and cytokines combat pathogens in the lungs. Macrophages in the alveoli and lymphoid tissue (tonsils) in the throat also contribute to defense. Secretory IgA in mucus secretions targets specific pathogens.

Normal Biota of the Respiratory Tract

Upper Respiratory Tract

  • Harbors thousands of commensal microorganisms.

  • Some normal biota can cause serious disease, especially in immunocompromised individuals. Examples include Streptococcus pyogenes, Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis, and Staphylococcus aureus.

  • Yeasts, such as Candida albicans, colonize mucosal surfaces of the mouth.

  • Other fungi can be found throughout the respiratory tract.

Lower Respiratory Tract

  • Normal biota is limited.

  • Composition differs in patients with lung disorders like COPD, asthma, and cystic fibrosis, as well as between smokers and non-smokers.

Microbial Antagonism

  • Normal biota performs microbial antagonism, competing for resources and space to prevent pathogens from establishing themselves.

  • Lactobacillus sakei in the sinus microbiome can suppress the pathogenic potential of Corynebacterium tuberculostearicum, reducing the incidence of sinus infection.

Upper Respiratory Tract Diseases Caused by Microorganisms

Pharyngitis

  • Signs and Symptoms: Inflammation of the throat (pharynx) causing pain and swelling. Severity ranges from moderate to severe based on causative agent. Viral sore throats are generally mild, sometimes leading to hoarseness. Bacterial sore throats are often more painful and accompanied by fever, headache, and nausea. Clinical signs include reddened mucosa, swollen tonsils, and sometimes white packets of inflammatory products on the throat walls (especially in streptococcal disease). Mucous membranes may be swollen, affecting speech and swallowing. Often results in foul-smelling breath. Incubation period is typically 2 to 5 days.

  • Causative Agents: Common cold viruses are the most frequent cause of sore throats. Pharyngitis can also result from mechanical irritation or sinus cavity drainage. The most serious cases are caused by Streptococcus pyogenes (group A streptococcus) and Fusobacterium necrophorum (anaerobic gram-negative bacterium).

Streptococcus pyogenes

  • Gram-positive coccus that grows in chains.

  • Non-endospore forming, nonmotile, forms capsules, facultative anaerobe, ferments various sugars.

  • Lacks catalase but has a peroxidase system to inactivate hydrogen peroxide.

  • Pathogenesis: Untreated streptococcal throat infections can result in complications. Post-streptococcal conditions can be caused by:

    • An extra toxin (scarlet fever).

    • Antigen-antibody complexes (glomerulonephritis).

    • Immune system attack of self tissues triggered by streptococcal "superantigens" (rheumatic fever and some types of obsessive-compulsive disorder).

Scarlet Fever

  • Results from infection with an S. pyogenes strain infected with a bacteriophage, giving it the ability to produce erythrogenic toxin.

  • Characterized by a sandpaper-like rash, most often on the neck, chest, elbows, and inner surfaces of the thighs, accompanied by high fever.

  • Historically had a high fatality rate (up to 95% in epidemic form).

Rheumatic Fever

  • Thought to be due to an immunologic cross-reaction between streptococcal M protein and heart muscle.

  • Occurs approximately 3 weeks after pharyngitis has subsided.

  • Can result in permanent damage to heart valves.

  • Other symptoms include arthritis in multiple joints and nodules over bony surfaces just under the skin.

  • Virulence Factors:

    • Surface antigens mimic host proteins.

    • Possession of superantigens.

  • Surface antigens:

    • Specialized polysaccharides on the cell wall protect bacterium from being dissolved by lysozyme.

    • Lipoteichoic acid (LTA) contributes to adherence to epithelial cells in the pharynx.

    • M protein resists phagocytosis and contributes to adherence.

    • Hyaluronic acid (HA) capsule contributes to adhesiveness.

  • Extracellular Toxins:

    • Streptolysins (SLO and SLS) cause beta-hemolysis of sheep blood agar and injure many cells and tissues.

    • Erythrogenic toxin causes the bright red rash typical of scarlet fever and induces fever.

    • Only lysogenic strains of S. pyogenes containing genes from a temperate bacteriophage can synthesize this toxin.

  • Transmission and Epidemiology:

    • Physicians estimate that 30% of sore throats may be caused by S. pyogenes.

    • Transmission is via respiratory droplets or direct contact with mucus secretions.

    • Humans are the only significant reservoir.

    • More than 80 serotypes exist, leading to possible multiple infections.

  • Culture and Diagnosis:

    • Children with severe sore throats should be tested for S. pyogenes.

    • Rapid diagnostic test kits detect group A streptococci from pharyngeal swab samples.

    • If needed, culture on sheep blood agar shows beta-hemolytic pattern due to streptolysins.

    • Newer testing techniques at the point of care (POC) take 15 minutes and don't require confirmation with culture. Newer tests using NAAT techniques are extremely accurate and don't require backup cultures.

  • Prevention: Good hand washing.

  • Treatment: Penicillin is the antibiotic of choice. Cephalexin (first-generation cephalosporin) is prescribed for patients with penicillin allergies.

Fusobacterium necrophorum

  • Causes severe sore throats and can progress to Lemierre's syndrome (bacterium invades the jugular vein and spreads to the circulatory system).

Viruses

  • Goal is to rule out S. pyogenes; further diagnosis usually not performed.

  • Treatment is symptom relief only.

  • Hoarseness frequently accompanies viral pharyngitis.

The Common Cold

  • Symptoms: Sneezing, scratchy throat, runny nose. Generally not accompanied by fever (children can experience low fevers of less than 102°F102°F).

  • Caused by over 200 different viruses, most commonly rhinoviruses (more than 150 serotypes), coronaviruses, and adenoviruses.

  • Respiratory syncytial virus (RSV) causes colds in most people, but can lead to more serious respiratory tract symptoms in infants and children.

Sinusitis

  • Inflammatory condition of the sinuses caused by allergy (most common), infections, or structural problems.

  • Infectious agents include viruses, bacteria (often mixed infection), and fungi.

  • Diagnosis is based on clinical presentation; X-rays or other imaging techniques may be used.

  • Treatment is none for viral sinusitis. For bacterial sinusitis, antibiotics are recommended only if it remains unresolved for some weeks. Fungal sinusitis requires physical removal of fungus or antifungals.

  • Viral and bacterial much more common than fungal

Acute Otitis Media (Ear Infection)

  • Viral infections of the upper respiratory tract can lead to inflammation of the eustachian tubes and fluid buildup in the middle ear, leading to bacterial multiplication.

  • The most common bacterium seen in acute otitis media is Streptococcus pneumoniae. There are currently four vaccine formulations for this bacterium.

  • Candida auris is a new cause of otitis media, difficult to diagnose and resistant to multiple antifungal drugs; it can spread from a localized ear infection to a bloodstream infection and can be fatal.

  • The current treatment recommendation for uncomplicated acute otitis media with a fever below 104°F104°F is "watchful waiting" for 72 hours, avoiding the use of antibiotics. In patients less than six months old, broad-spectrum antibiotics should be considered. Children who experience frequent recurrences of ear infections sometimes have small tubes placed through the tympanic membranes for fluid drainage.

Lower Respiratory Tract Diseases Caused by Microorganisms

Pneumonia

  • An inflammatory condition of the lung in which fluid fills the alveoli.

  • Can be caused by bacteria, fungi, and viruses.

  • Microorganisms must avoid being phagocytosed by alveolar macrophages, or at least avoid being killed once inside the macrophage.

  • More children under the age of 5 die from pneumonia than any other infectious disease across the globe.

Physicians distinguish between two forms:

  • Community-Acquired Pneumonia (CAP): Experienced by persons in the general population.

  • Healthcare-Associated Pneumonia (HCAP): Develops in individuals receiving treatment at health care facilities.

Causative Agents of Community-Acquired Pneumonia

  • SARS-CoV-2

  • Streptococcus pneumoniae

  • Legionella species

  • Mycoplasma pneumoniae

  • Chlamydophila pneumoniae

  • Histoplasma capsulatum

  • Hantavirus.

  • Many, deaths stemming from the influenza virus are caused by pneumonia, either from the original virus or from secondary infection.

Streptococcus pneumoniae

  • Small gram-positive flattened coccus that often appears in pairs lined up end to end.

  • Alpha-hemolytic on blood agar.

  • Factors that favor its ability to cause disease: old age, the season (rate of infection is highest in the winter), underlying viral respiratory disease, diabetes, and chronic abuse of alcohol or narcotics.

  • Older adults are encouraged to seek immunization with the pneumococcal vaccines PCV15 or PCV20.

Legionella pneumophila

  • Weakly gram-negative bacterium that has a range of shapes, from coccus to filaments.

  • Resistant to chlorine.

  • Can live in close association with free-living amoebas.

  • Cases have been traced to supermarket vegetable sprayers, hotel fountains, air-conditioning vents, and even misting towers at Disney parks.

Mycoplasma pneumoniae

  • Causes pneumonia that is often called atypical pneumonia because the symptoms do not resemble those of pneumococcal or other severe pneumonias.

  • Transmitted by aerosol droplets among people confined in close living quarters.

  • Lack of acute illness in most patients has given rise to the name "walking pneumonia."

Hantavirus

  • Causes hantavirus pulmonary syndrome (HPS).

  • Transmitted via airborne dust contaminated with the urine, feces, or saliva of infected rodents.

  • Deer mice and other rodents can carry the virus with few apparent symptoms.

Histoplasma capsulatum

  • Grows most abundantly in moist soils high in nitrogen content, especially those supplemented by bird and bat droppings.

  • In high-prevalence areas such as southern Ohio, Illinois, Missouri, Kentucky, Tennessee, Michigan, Georgia, and Arkansas, 80% to 90% of the population show signs of prior infection.

Pneumocystis jirovecii

  • Agent of Pneumocystis pneumonia (PCP), one of the most frequent opportunistic infections in AIDS patients.

  • Cancer patients and others with extreme immunosuppression are also at risk for this disease.

Respiratory Viruses

  • Are very common causes of community-acquired pneumonia.

  • Viral pneumonias are generally mild.

  • Human metapneumovirus can now be tested for via RT-PCR or immunoassay.

Healthcare-Associated Pneumonia

  • Up to 1% of hospitalized or institutionalized people experience the complication.

  • The mortality rate is quite high-between 30% and 50%.

  • The most frequent cause of all forms of healthcare-associated pneumonia today are MRSA strains of Staphylococcus aureus, as well as nonresistant strains.

  • After MRSA, gram-negative bacteria are most common: Klebsiella pneumoniae, Enterobacter, E. coli, Pseudomonas aeruginosa, and Acinetobacter.

  • Measures that discourage the transfer of microbes into the lungs are very useful for preventing the condition: Elevating patients' heads to a 30-to 45-degree angle helps reduce aspiration of secretions. Good preoperative education of patients about the importance of deep breathing and frequent coughing can reduce postoperative infection rates. Proper care of mechanical ventilation and respiratory therapy equipment is essential as well.

  • Even in this era of conservative antibiotic use, empiric therapy should be started as soon as healthcare-associated pneumonia is suspected, using multiple antibiotics that cover both gram-negative and gram-positive organisms.

Influenza

Signs and Symptoms

  • Influenza begins in the upper respiratory tract but in serious cases may also affect the lower respiratory tract.

  • Symptoms include headache, chills, dry cough, body aches, fever, stuffy nose, and sore throat.

Causative Agent

  • Three influenza viruses: A, B, or C. They belong to the family Orthomyxoviridae.

  • The two glycoproteins that make up the spikes of the envelope and contribute to virulence are called hemagglutinin (H) and neuraminidase (N).

Antigenic Shift/Drift

  • Antigenic drift: Constant mutation of the glycoproteins - the antigens gradually change their amino acid composition, resulting in decreased ability of host memory cells to recognize them. Antigenic drift is the reason that a new vaccine is required for each year.

  • Antigenic shift: Swapping out one of those genes or strands with a gene or strand from a different influenza virus.

  • Influenza A viruses are named according to the different types of H and N spikes they display on their surfaces.

Pathogenesis and Virulence Factors

  • The influenza virus binds primarily to ciliated cells of the respiratory mucosa. Infection causes the rapid shedding of these cells along with a load of viruses.

  • Stripping the respiratory epithelium to the basal layer eliminates protective ciliary clearance.

Transmission and Epidemiology

  • Inhalation of virus-laden aerosols and droplets is the major route of influenza infection, although fomites can play a secondary role.

  • The drier air of winter facilitates the spread of the virus, as the moist particles expelled by sneezes and coughs become dry very quickly, helping the virus remain airborne for longer periods of time.

Prevention

  • Preventing influenza infections and epidemics is one of the top priorities for public health officials. There are currently several types of vaccines.

Treatment

  • Influenza is one of the first viral diseases for which effective antiviral drugs became available.

  • The drugs should be taken early in the infection, preferably by the second day.

  • Zanamivir (Relenza) is an inhaled drug that works against influenza A and B. Oseltamivir (Tamiflu) is available in capsules or as a powdered mix to be made into a drink. It can also be used for prevention of influenza A and B. A new drug, baloxavir (trade name Xofluza), was approved in 2018.

Whooping Cough (Pertussis)

  • There are two distinct symptom phases:

    • The catarrhal phases:
      Bacteria present in the respiratory tract cause what appear to be cold symptoms, most notably a runny nose.

    • The paroxysmal: Characterized by severe and uncontrollable coughing (a paroxysm can be thought of as a convulsive attack). The common name for the disease comes from the whooping sound a patient makes as they try to grab a breath between uncontrollable bouts of coughing.

Respiratory Syncytial Virus Infection

  • Infects the respiratory tract and produces giant multinucleated cells (syncytia).

  • Spread through droplet contact and fomite contamination.

  • Afflicted child is conspicuously ill, with signs typical of pneumonia and bronchitis.
    2022-2023 Tripledemic:
    RSV infections surged earlier in the season than usual in children, along with influenza and SARS-CoV-2 infections, in what came to be called the "tripledemic."

Tuberculosis

  • An ancient human disease caused by Mycobacterium tuberculosis.

Signs and Symptoms

  • Most cases are contained in the lungs, though disseminated TB bacteria can result in tuberculosis in any organ of the body.

  • Classifications:

    • Primary Tuberculosis: Occurs after initial infection.

    • Secondary (Reactivation) Tuberculosis: Bacteria is reactivated and causes chronic tuberculosis.

    • Disseminated or Extrapulmonary Tuberculosis: TB infection outside of the lungs is more common in immunosuppressed patients and young children.

Causative Agents

  • M. tuberculosis, an acid-fast rod, strict aerobe, and slow-growing bacterium.

Pathogenesis and Virulence Factors

  • Waxy surface contributes to survival in the environment and within macrophages.

  • Ability to stimulate a strong cell-mediated immune response contributes to the pathology of the disease.

Transmission and Epidemiology

  • Transmitted almost exclusively by fine droplets of respiratory mucus suspended in the air.

Culture and Diagnosis

  • Clinical diagnosis relies on three techniques:

    • Tuberculin testing.

    • Interferon-gamma release assays (IGRAs) performed on a blood sample.

    • Gene amplification and antimicrobial susceptibility testing.

  • Acid-fast staining.

Prevention

  • Limiting exposure to infectious airborne particles.

  • Use of BCG vaccine in many countries outside of the U.S.
    Treatment:

  • Three drugs: isoniazid, rifampin, and rifapentine: noncompliance has led to multidrug-resistant TB.

Multidrug-Resistant Tuberculosis (MDR-TB)

  • Defined as being resistant to at least isoniazid and rifampin.

Extensively Drug-Resistant Tuberculosis (XDR-TB)

  • MDR-TB strains with resistance to two additional drugs.
    Many healthcare-associated pneumonias appear to be polymicrobial in origin

The Gastrointestinal Tract and Its Defenses

Gastrointestinal (GI) Tract

  • Long tube extending from mouth to anus, serving as a delivery system for nutrients.

  • Composed of eight main sections: mouth, pharynx, esophagus, stomach, small intestine, large intestine, rectum, and anus.

  • Assisted by four accessory organs: salivary glands, liver, gallbladder, and pancreas.

Defenses Against Infection

  • Intestinal surfaces coated with mucus for mechanical protection.

  • Secretory IgA on most intestinal surfaces.

  • Muscular walls promoting peristalsis.

  • Antimicrobial properties: lysozyme and lactoferrin in saliva, high acidity in stomach fluid, antimicrobial bile.

  • Gut-associated lymphoid tissue (GALT): tonsils and adenoids, lymphoid tissue in esophagus, Peyer's patches in small intestine, appendix; consists of T and B cells as well as cells of the innate immunity.

Normal Biota of the Gastrointestinal Tract

Oral Cavity

  • Populated by more than 600 known species of microorganisms, including Actinomyces, Lactobacillus, Neisseria, Prevotella, Streptococcus, Treponema, and Veillonella species.

  • Fungi such as Candida albicans are also numerous. Bacteria present in:

    • Teeth:
      synergistic community called dental plaque.

    • Pharynx (throat):
      Variety of microorganisms.

    • Stomach:
      many species of microorganisms Bacillus, Clostridium, Staphylococcus, and Streptococcus, are permanent residents.

Large Intestine

Haven for billions of microorganisms:
* Bacteria: Bacteroides, Bifidobacterium, Clostridium, Enterobacter, Escherichia, Fusobacterium, Lactobacillus, Peptostreptococcus, Staphylococcus, and Streptococcus.
* Fungus: Candida.
* Archaea and Protozoa.

Clear that the gut microbiome influences the development of the nervous system, including portions of the brain and can have effects on behavior and neurological wellness.

Organ influence:

  • Endocrinologists connect contribute to the development of type 2 diabetes.

  • Gut Protective function and help with digestion.

  • E. coli synthesizes vitamin K.
    The presence plays an important role in teaching our immune system to react to microbial antigens.

Term- Dysbiosis

Variety of microbes in the gut decreases, and certain bacteria come to dominate.

Accessory Organs

  • Are free of a natural microbiome but can be exposed to microbes when normal barriers in the gut are disrupted by dysbiosis.

Gastrointestinal Tract Diseases Caused by Microorganisms (Nonhelminthic)

Acute Diarrhea

Most common culprits

  • Norovirus

  • Salmonella

  • Campylobacter

  • Clostridium perfringens

  • Staphylococcus aureus

Highlights on Bacteria that cause bacteria

  • Salmonella: most, too, produce hydrogen sulfide (H2S) but not urease.

  • Shigella: gram-negative rods, nonmotile and non-endospore-forming. They are bacterial that resemble some types of pathogenic E. coli very closely.

Shiga-Toxin-producing E. coli (STEC)

  • Cause bloody diarrhea known for systemic effects.

Campylobacter jejuni

  • Is now known heat-labile enterotoxin

  • Clostridioides difficile - noninvasive, enterotoxins A and B, cause areas of necrosis, 66% of cases are healthcare-associated.

  • Vibrio cholerae - secretory diarrhea, Fluid losses of nearly 1 liter per hour have been reported in severe

Other Causes

  • Cryptosporidium

  • Rotavirus

  • Norovirus

Food Poisoning

  • Usually, severe nausea followed by diarrhea when a recent shared meal is a commonality.

  • Staphylococcus aureus Exotoxin heat-stable; antibiotic treatment is not warranted.
    -Bacillus cereus Exotoxin Proper food handling is the best way to avoid this - diarrhea/vomiting.

  • Clostridium perfringens Exotoxin - food borne, rapid recovery, and deaths are rare.

C. perfringens also causes an enterocolitis infection similar to that caused by C. difficile.

Chronic Diarrhea

  • Chronic diarrhea is defined as lasting longer than 14 days.

  • EAEC is bacterial is particularly associated with chronic disease, especially in children.

  • C. cayetanensis protozoan is related most cases have been associated with consumption of fresh produce and water presumably contaminated with feces.

  • Giardia d. Flagellated Protozoan- stools have a greasy, foul-smelling quality to them

  • E. histolytica - Dysentery, is the initial form where the targets are the cecum, appendix, colon, and rectum. The Amoeba secretes enzymes that break down the intestines

Tooth and Gum Infections

  • Two categories: dental caries and periodontitis.

  • Dental caries polymicrobial

  • Periodontitis is caused the right combination of the anaerobes Tannerella forsythia , formerly Bacteroides forsythus, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Fusobacterium and spirochete .
    Dysbiosis increase the risk of diabetes, coronary diseases, autoimmune issues

Mumps

  • Spike-induced syncytium formation.

  • MMR live attenuated vaccine;

Gastritis and Gastric Ulcers

  • The cause is bacterial Helicobacter pylori. the treatment is acid suppression and antibiotics - 50% infection rate, and - is now known to also create adhesions that have ability called urease with direct transfer from person's oral-oral or fecal.
    It is noted that not be confused to fungi. colonies resembling colony fungi but it is instead bacteria that has cord growth by unknown causes

The Genitourinary Tract and Its Defenses

Urinary Tract

  • The urinary tract includes the kidneys, ureters, bladder, and the urethra.

  • Male: The urethra houses fluids such as urine and ejaculate.

Defensive Mechanisms

  • Flushing action of urine and shedding of ep epithelial walls

  • Lysozyme/Lactoferrin - are bacterial chemicals that breakdown in high acidity in both reproductive systems.

Reproductive System Female

It consists of the uterus, the fallopian tubes (also called uterine tubes), ovaries, vagina, and cervix:
Mucus - A good portion of The defense comes into action with a change of PH with the female sex releases glycogen, and is changed the biota with their pH

Normal Microbiota Female: Variable LActobavccilus, Prevotella

Male Reproductive System

-Flushing action of the urine.
-Testes with epididmyis and vas deferens.
-The Prostrate Gland is located under the male urethra.
outer penis: pseudomonas and staphylococcus Sulcus - anaerobic bacteria

Urinary Tract Diseases Caused By Microorganisms

A urinary tract infection (UTI) comes in two forms. bladder or kidneys. - usually is bacterial transmission or catheter based

Escherichia coli is the number on one factor and also with the same type of family, Enterobacteriacea.

Leptospirosis

Known for spirochetes that infect broken dermi skin.
It is from animal exposure (such as animals urine.
With is a zoonoses that starts one with flu like symptoms, kidney failure and more (Weil syndrome).
Has two phases: early with the pathogen present; clear by body defenses and late mild fever meningitis

Treatment - Doxcycline