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Questions and Answers
What is one of the main reasons for tuberculosis being a leading cause of death globally?
What is one of the main reasons for tuberculosis being a leading cause of death globally?
Which characteristic is NOT true about the Mycobacterium tuberculosis?
Which characteristic is NOT true about the Mycobacterium tuberculosis?
Which group is at the highest risk for contracting tuberculosis in the US?
Which group is at the highest risk for contracting tuberculosis in the US?
How many estimated new cases of tuberculosis occur yearly worldwide?
How many estimated new cases of tuberculosis occur yearly worldwide?
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Which of the following species of Mycobacterium is most important in humans?
Which of the following species of Mycobacterium is most important in humans?
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What type of pathogens are Chlamydia and Chlamydophila considered?
What type of pathogens are Chlamydia and Chlamydophila considered?
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In which form are Chlamydia infectious?
In which form are Chlamydia infectious?
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What mechanism allows Chlamydia to evade the host immune response?
What mechanism allows Chlamydia to evade the host immune response?
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Why has the creation of a vaccine for Chlamydia trachomatis been challenging?
Why has the creation of a vaccine for Chlamydia trachomatis been challenging?
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Which of the following hosts are primarily affected by Chlamydia psittaci?
Which of the following hosts are primarily affected by Chlamydia psittaci?
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What role do transporter proteins play in Chlamydia's survival?
What role do transporter proteins play in Chlamydia's survival?
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Which symptom is NOT typically associated with Chlamydia pneumoniae infections?
Which symptom is NOT typically associated with Chlamydia pneumoniae infections?
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Which serotypes of Chlamydia trachomatis are associated with lymphogranuloma venereum?
Which serotypes of Chlamydia trachomatis are associated with lymphogranuloma venereum?
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What is the primary method of transmission for Chlamydia trachomatis in cases of trachoma?
What is the primary method of transmission for Chlamydia trachomatis in cases of trachoma?
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What is a common complication of untreated urogenital infections caused by C. trachomatis in females?
What is a common complication of untreated urogenital infections caused by C. trachomatis in females?
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Which condition is primarily linked to chronic inflammation caused by repeated infections of trachoma?
Which condition is primarily linked to chronic inflammation caused by repeated infections of trachoma?
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What characteristic distinguishes the serovars causing trachoma from those causing urogenital infections?
What characteristic distinguishes the serovars causing trachoma from those causing urogenital infections?
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Which demographic is most impacted by trachoma?
Which demographic is most impacted by trachoma?
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What primarily causes neonatal conjunctivitis associated with C. trachomatis?
What primarily causes neonatal conjunctivitis associated with C. trachomatis?
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Which of the following complications can arise in males due to untreated C. trachomatis infections?
Which of the following complications can arise in males due to untreated C. trachomatis infections?
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The leading cause of preventable blindness worldwide is due to which condition?
The leading cause of preventable blindness worldwide is due to which condition?
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Which condition is most commonly caused by infection with trachomatis in newborns?
Which condition is most commonly caused by infection with trachomatis in newborns?
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What is the primary route of transmission for Chlamydophila pneumoniae?
What is the primary route of transmission for Chlamydophila pneumoniae?
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Which of the following is a common clinical manifestation of Chlamydophila pneumoniae infection?
Which of the following is a common clinical manifestation of Chlamydophila pneumoniae infection?
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What percentage of adults show serologic evidence of prior Chlamydophila pneumoniae infection?
What percentage of adults show serologic evidence of prior Chlamydophila pneumoniae infection?
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What is the typical incubation period for Chlamydophila pneumoniae?
What is the typical incubation period for Chlamydophila pneumoniae?
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In the case of the renal transplant recipient, which lab finding is consistent with a significant inflammatory response?
In the case of the renal transplant recipient, which lab finding is consistent with a significant inflammatory response?
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Which symptom is least likely to be associated with Chlamydophila pneumoniae infection?
Which symptom is least likely to be associated with Chlamydophila pneumoniae infection?
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What is a key characteristic of atypical pneumonia caused by Chlamydophila pneumoniae?
What is a key characteristic of atypical pneumonia caused by Chlamydophila pneumoniae?
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Which demographic is most likely to experience outbreaks of Chlamydophila pneumoniae infections?
Which demographic is most likely to experience outbreaks of Chlamydophila pneumoniae infections?
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Which finding from the renal transplant recipient's case might suggest respiratory involvement?
Which finding from the renal transplant recipient's case might suggest respiratory involvement?
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What was the most effective medium for growing Legionella pneumophila during the patient's hospitalization?
What was the most effective medium for growing Legionella pneumophila during the patient's hospitalization?
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Which characteristic primarily hinders the Gram staining procedure for Legionella pneumophila?
Which characteristic primarily hinders the Gram staining procedure for Legionella pneumophila?
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How does Legionella pneumophila typically infect humans?
How does Legionella pneumophila typically infect humans?
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What is a common feature of Legionella pneumophila observed in infected tissues?
What is a common feature of Legionella pneumophila observed in infected tissues?
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What key factor allowed for the identification of Legionella pneumophila in this case?
What key factor allowed for the identification of Legionella pneumophila in this case?
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Legionella pneumophila is most notably associated with which type of disease?
Legionella pneumophila is most notably associated with which type of disease?
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Which serotypes of Legionella pneumophila are responsible for the majority of human infections?
Which serotypes of Legionella pneumophila are responsible for the majority of human infections?
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What key action can help prevent infections caused by Legionella pneumophila?
What key action can help prevent infections caused by Legionella pneumophila?
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What is the primary reservoir for Legionella pneumophila in the environment?
What is the primary reservoir for Legionella pneumophila in the environment?
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What method was used for counterstaining in the Gram-stained photomicrograph of Legionella pneumophila?
What method was used for counterstaining in the Gram-stained photomicrograph of Legionella pneumophila?
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Study Notes
Atypical Bacteria - Part 1
- Atypical bacteria are categorized as intracellular or extracellular
- Intracellular bacteria include Chlamydia, Legionella, Mycobacterium, and Rickettsiales, among others.
- Extracellular bacteria include Mycoplasma, Spirochetes (Leptospira, Borellia, Treponema), etc.
- Key bacteria covered in this lecture include Chlamydia and Chlamydophila, Legionella, and Mycobacterium.
Recommended Reading and Learning Objectives
- Review appropriate chapters from medical microbiology
- Describe each pathogen's cell wall properties (intracellular or extracellular)
- Detail the pathogen's natural habitat (human, animal, soil, etc.)
- Explain transmission mechanisms
- Identify clinical manifestations of diseases
- Describe pathogenicity, linking virulence factors
- Explain diagnostic features
Case Study
- A 19-year-old male presented to an STD clinic, with a purulent urethral discharge
- A gram stain revealed no gram-negative diplococci
- The most likely clinical diagnosis is non-gonococcal urethritis
- Possible etiological diagnoses are: Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium, and Trichomonas vaginalis
Chlamydia and Chlamydophila
- Worldwide human pathogens
- They do not gram stain, but have characteristics similar to gram-negative bacteria
- Outer membrane, LPS
- Obligate intracellular pathogens; require cell culture for isolation
- Once thought to be viruses, but have DNA, RNA, and ribosomes, and make their own macromolecules.
- Obtain energy from host ATP
- Unique life cycle in two forms: elementary bodies (EB) and reticulate bodies (RB)
- EB are metabolically inactive, infectious
- RB are metabolically active, non-infectious
- Chlamydia's life cycle includes attachment, transcription of DNA, RNA and protein synthesis, binary fission, and continued multiplication
- Persistent infection possible with presence of gamma-IFN
- Chlamydia trachomatis is the species of importance, with types concerning ocular, genital, and invasive infections
- Different subtypes (serotypes) of C. trachomatis cause different diseases (trachoma, genital, lymphogranuloma)
Virulence Factors of Chlamydia
- Intracellular replication in numerous cell types
- Safe from complement, antibodies, and phagocytosis
- Prevent fusion of endosome with lysosome
- Endosome becomes inclusion body for replicating RBs
- Transport proteins (IncA, etc.) facilitate nutrient uptake from cytoplasm into inclusion body
- Secretion systems function as "molecular straws" transporting nutrients, and inhibit apoptosis
- Proteins also inhibit MHC Class I expression, decreasing antigen presentation to CD8 cells
Pathogenesis of Chlamydia trachomatis
- Elementary bodies enter epithelial cells of conjunctiva and urogenital tracts
- Organism replicates as previously described.
- Infected cells release inflammatory mediators (IL-1, IL-8, others) leading to acute, then chronic inflammation.
- Disease manifestations result from chronic inflammation, tissue reorganization, and scarring, especially if left untreated
- Infected cells stimulated with gamma-IFN can temporarily halt replication but not kill RBs
- The lack of this inhibition may lead to chronic infection
- Gamma -IFN induces the expression of indoleamine-2,3-dioxygenase (IDO) which degrades tryptophan. This reduced tryptophan leads to the death of Chlamydia spp. through tryptophan starvation. However, some reticulate bodies acquire a non-replicating, but viable, persistent form. Removing IFN-gamma and replenishing tryptophan causes re-differentiation into infectious elementary bodies.
Important Members of the Chlamydia family
- C. trachomatis causes ocular infections, genital infections, and neonatal infections. Many serotypes make vaccine creation difficult and cause repeat infections.
- C. pneumoniae causes respiratory infections
- C. psittaci, a bird pathogen, causes psittacosis in humans
- Flu-like illness with lower respiratory symptoms associated with bird excretion
Legionella pneumophila
- Gram-negative bacteria that do not stain well with Gram stain.
- Pleomorphic in culture (have several forms in different settings)
- Legionella pneumophila serotypes 1 and 6 cause over 90% of human infections
Transmission and Epidemiology of Legionella sp.
- Aquatic saprophytes that live in biofilms and amoebae in water
- Found in wide variety of natural and man-made water sources (lakes, rivers, ponds, showers, fountains, spas, etc.)
- Transmitted through water mist inhalation.
- Survive high temperatures and treatment with chlorine.
Legionella in Man-Made Water Sources
- Pathogenic Legionella can produce aerosols in engineered and natural water-systems, leading to lung infections, resulting in Legionellosis
Legionnaires' Disease/Legionellosis
- Community-acquired and hospital-acquired pneumonia
- ~10,000 reported cases per year in the US.
- Risk factors include elderly, patients with smoking, renal, or liver disease, diabetes, immune suppression (e.g., from cancer or AIDS), transplantation, and corticosteroid use.
- Pontiac Fever, a milder disease, is also associated with Legionella
Pathogenesis of Legionnaires' disease
- Infection through inhalation, resulting in growth in alveolar macrophages
- Inhibit formation of phagolysosome, surrounding phagosome with materials from endoplasmic reticulum
- Incubation period is 2-10 days
- Symptoms are abrupt onset of fever, chills, nonproductive cough, and headache
Diagnosis of Legionellosis
- Clues include pneumonia with both pulmonary and nonpulmonary symptoms, negative sputum gram stain
- PCR, urine antigen test, and culture using buffered charcoal yeast extract (BCYE)
Prevention of Legionella Infection
- Superheating of water to 70-80°C
- Installing copper-silver ionization units
Tuberculosis
- A contagious disease caused by Mycobacterium tuberculosis
- Person-to-person transmission occurs through inhaling droplets from a cough or sneeze.
- Global health concern
Global Impact of Tuberculosis
- One of the leading causes of death worldwide
- Estimated 1/3 of world population is infected.
- Estimated 8 million new cases annually.
- 1.5-3.0 million people die annually from tuberculosis
- Antibiotic resistance is a major problem.
Mycobacterium
- Acid-fast, aerobic rods.
- Cell wall contains lipids, making them resistant to chemicals and drying
- Important species include M. tuberculosis, M. leprae, and M. intracellulare
- M. tuberculosis (TB)
- M. leprae (leprosy), with pockets of high endemicity
- M. intracellulare, a disseminated disease in immune-compromised individuals
TB Incidence & Risk Factors
- TB incidence varies geographically
- Foreign-born people from high-TB countries, close contacts, people in high-risk congregate settings (prisons/shelters), HIV/AIDS patients, injection drug users, medically underserved and low-income populations have elevated risk.
Pathogenesis of Mycobacterium tuberculosis
- Inhalation of droplets containing bacteria
- Bacteria access lungs and replicate within alveolar macrophages
- Replication progresses very slowly
- Outcome depends on host immune response; Latent or active infection
Latent Infection
- Bacteria are contained by granulomas, preventing replication, but staying viable for years/decades
- Over time, granulomas can turn into calcified nodules (Gohn complex).
Active Infection (Pulmonary)
- Majority of people develop miliary TB (usually in immune compromised people/children).
- Pulmonary TB; TB primarily in the lung
- Secondary (reactivated) TB
- Immune suppression allows latent TB to reactivate, resulting in granuloma breakdown and releasing organisms into the body
Primary vs Reactivated Pulmonary TB
- Primary infection and ensuing pulmonary disease is more common in children and less in adults.
- Reactivated TB infection and disease is more common in adults whose immune system is compromised.
Manifestations of Reactivated Pulmonary TB
- Insidious onset of fever, night sweats, weight loss, anorexia, malaise, and weakness.
- Productive cough, often with blood-streaked sputum
- Apical and posterior segments of upper lobes are most often affected
- Cavitary lesions in CXR are indicative of reactivated pulmonary TB
Miliary (Non-Pulmonary) TB
- Miliary TB is a disseminated form of TB
- Can affect lymph nodes, meninges (meningitis).
- Back pain associated with Potts disease/involvement of the spine is common
- Chronic arthritis
- Gastrointestinal system involvement, including ulcers, malabsorption, and diarrhea
Diagnosis of Active TB
- TB skin test or interferon gamma release assay
- Acid-fast stain of sputum
- Sputum sample for nucleic acid detection, culture and sensitivity testing.
- NA detection using RNA probes
- PCR can detect M. tuberculosis.
Treatment of TB
- Directly observed therapy is a globally used method to encourage patient compliance
- Latent TB is treated with a 2-drug regimen for 9 months
- Active TB is treated with 4-drug regimen for both two and longer periods of time, depending on resistance and severity
Case Study - Mycobacterium avium complex (MAC) infection
- A 23-year-old AIDS patient with a 3-month history of fever, night sweats, fatigue, weight loss (22 pounds), and diarrhea.
- Low CD4 count (below 50/mm3) and high viral load (55,000/mm3) for the preceding several months.
- Routine blood cultures negative after 48 hrs but grew after ten days
- DNA probes identified Mycobacterium avium complex organisms.
Pathogenesis of Disseminated MAC in AIDS Patients
- Disseminated infection in severely immunocompromised patients with CD4 counts below 50/uL
- Organism enters body through ingestion or inhalation, crosses mucosal epithelium and infects macrophages
- Macrophages carry the organism throughout the body to other organs.
- Macrophages replicate the organisms and secrete a variety of cytokines.
- High burden of microbes in macrophages causes a "cytokine storm" that leads to widespread inflammation and tissue harm.
Questions regarding the case study and organisms.
- Diagnostic features of organisms
- Sources of organisms
- Other diseases caused by organism presented in case study
- Treatment options
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Description
Test your knowledge on atypical bacteria categorized as intracellular or extracellular. This quiz covers pathogens like Chlamydia, Legionella, and Mycobacterium, including their characteristics, habitats, and clinical manifestations. Review key concepts from medical microbiology to excel in this assessment.
