MIC 401 Module 4

Mycobacteria

slow growing bacilli; aerobic to microaerophilic; doubling time is 18-24 hours, 4-6 weeks on average for visible colonies on agar plate; mycolic acid rich cell wall (key virulence factor); termed acid fast bacilli (stained with acid fast or fluorescent stains)

Mycobacteria - Mycolic Acid Cell Wall

unique, thick, hydrophobic, waxy, long fatty acids; hardy and resistant to chemicals, acids, dehydration, detergents, most standard antibiotics, and immune defenses; prevents characterization by gram staining (resist standard acid containing destaining solutions)

Mycobacteria - Human Medical Importance

over 190 species in this genus; most found widespread in environment, associated with water and animals; classified into three main groups that cause disease: tuberculosis complex, leprae/lepromatosis, NTM/MOTT

Mycobacteria Tuberculosis/Mtb - Transmission and Disease

human respiratory tract bacterial pathogen; major route of transmission is inhalation of contaminated droplets from an infected person (breathing, coughing, sneezing, speaking, singing); not spread via shaking hands or contact with fomites; pulmonary and extrapulmonary TB

Mtb - Extrapulmonary TB

infections outside the respiratory tract; can infect gastrointestinal tract, bones, joints, nervous system, lymph nodes, genitourinary tract, and skin; symptoms depend on anatomical location of infection (blood in urine if kidneys are infected, back pain if spine is infected)

Mtb - Reservoir

humans are the only known reservoir (obligate human parasite); today it is the deadliest infectious disease worldwide

Mtb - History

epidemic in western europe (1600-1800s); termed the white plague and consumption due to extreme paleness, fatigue, and weight loss as patients wasted away, becoming increasingly weakened and thin before dying (consumed by the disease); 25% of the eurpean population died

Mtb - Pulmonary TB

transmitted via inhalation of infectious air droplets emitted from a person with the disease; 3 possible outcomes: infection eliminated, latent infection, subclinical/active disease

Pulmonary TB - Infection Eliminated

with innate or acquired immune response; it is the best outcome, bacteria do not establish infection or initial infection is eradicated by immune system

Pulmonary TB - Latent Infection

90% of infections; inhaled Mtb not fully eliminated, but controlled in a dormant state within granuloma (walled off); asymptomatic infection, 1/3 of the world’s population

Pulmonary TB - Subclinical Disease/Active Disease

persons with LTBI may progress to active disease (10%); immediately to decades after initial infection; severity of disease determined by host immune response

Mtb - Symptoms of Active TB

classic symptom is chronic, productive coughing (>3 weeks); bloody sputum indicative of lung damage and invasive disease; other common symptoms include fever, night sweats, weight loss, loss of appetite, fatigue, shortness of breath; may disseminate from the lungs and infect almost any extrapulmonary site (CNS, bone, lymph nodes); disease and symptom severity correlated with immune response; devastating in HIV/AIDS individuals

Mtb - Risk Factors

recent airborne exposure'; close contacts with an active infected person; people who live or work in areas with high rates/high risks of infection (homeless, IV drug users, HIV, correctional facilities, nursing homes, shelters); people with weakened immune systems due to medical or socioeconomic conditions

Mtb - Detection and Diagnosis

tuberculin skin test; diagnosis of active disease is based on clinical manifestations, abnormal chest radiograph, acid fast bacilli in sputum, DNA detection tests (NAATs) of sputum

Tuberculin Skin Test

injection of a small amount of Mtb purified protein derivative (PPD) solution under the first layer of skin of the forearm; evaluation of injection site at 48 and/or 72 hours to measure local skin reaction

Mtb - Active TB Treatment

6-9 months of 4 drug regimen (isoniazid, rifampin, pyrazinamide and ethambutol); more added if multi-drug resistant (global health emergency); HIV infected individuals need >/= 1 year of treatment

Mtb - Latent TB Treatment

3-6 month prophylactic antibiotics; TST positive with no signs or symptoms of active disease

Mtb - Prevention

BCG used under select circumstances; infection control; prompt testing if traveled to high rate regions (SE asia, east europe, south america), had direct exposure to infection, or workin health care, nursing homes, correctional facilities, homeless shelters, etc; consume only pasteurized dairy products to prevent bovine TB

Mtb - BCG Vaccine

used in countries with high prevalence of TB to prevent childhood disease; not effective against adult TB; interferes with TST reactivity and screening (can give false positives)

Mycobacterium Leprae

slow growing obligate intracellular AFB; longest doubling time of all known bacteria; grows optimally at cooler temperatures; invades skin macrophages and schwann cells, inducing skin lesions and neurological injury; first bacterium to be identified as causing disease in humans; causes hansen’s disease/leprosy

Schwann Cells

in peripheral nervous system; form the myelin sheath around a neuron’s axon

M.leprae - Hansen’s Disease

chronic, granulomatous disease; slowly developing, progressive, chronic infection results in inflammatory nodules in the skin and peripheral nerves over time; bacterium targets the peripheral nerves and skin layers of the extremities, ears, and noses which are much cooler than the trunk of the body

M.leprae - Untreated Disease

inflammatory damage can lead to blindness, crippling of the hands and feet, loss of digits, facial disfigurement (especially loss of nose/ear tissues), and paralysis

M.leprae - Historical Transmission

primarily spread person to person but not very contagious; transmitted by inhalation of infectious respiratory droplets or direct contact with broken skin; prolonged, close contact with untreated patient over many months to years needed for infection to be transmitted

M.leprae - Recently Found Transmission Pattern

some human cases are zoonotic; transmitted to humans by infectious chimpanzees, certain monkey species, and in the U.S. by nine banded armadillos to humans by direct contact or respiratory droplets

M.leprae - Ongoing Research Transmission Patterns

possible insect vector (ticks); environmental reservoir (amoebas/feral macrophages, moist soil, mosses, water)

M.leprae - Infection

even with confirmed exposure, 95% of people have a natural immunity to the disease (large genetic component to susceptibility); incubation period ranges between 6 months and 20+ years (3-5 years avg); abx cure the infection; people receiving treatment do not need to be isolated (vs leper colonies of the past); over 15 million people have been cured, but the disease is still responsible for disfiguring or disabling 2-4 million people

M.leprae - Prevalence

about 600 people are diagnosed each day; over 3 million people are living with undiagnosed infection

M.leprae - Risk Factors for Disease

living where leprosy is endemic (india, brazil, nepal, africa); close contact with infected/untreated people or animals; frequent handling of animals known to carry the bacteria (armadillos, african chimp, sooty mangaby, cynomolgus macaque); having specific genetic immune system defects

M.leprae - Disease Signs and Symptoms

subtle, occur slowly (usually over years), begin in cooler areas of the body (hands, feet, face, knees); discolored, numb skin patch (often first sign of infection); progressive numbness of affected areas; loss of temperature and touch sensation; pins and needles sensations

M.leprae - Untreated Chronic Inflammation

multiple skin lesions of hypo/hyperpigmented macules (flat, discolored areas), ulcers, blisters, and/or rashes; eye damage (dryness, reduced blinking); ear disfigurement; hair loss (including loss of eyebrows); nerve injury; severe disfigurement and damage to the extremities

M.leprae - Diagnosis

critical and based on 3 main criteria: hypopigmented or reddish skin patches with loss of sensation, thickened peripheral nerves, AFB detected on skin smears or biopsy material

M.leprae - Treatment

100% curable with long term, multi-drug antibiotic therapy (1-2 years); early diagnosis imperative; treatment will cure infection but not reverse nerve damage or physical disfiguration; BCG vaccine may offer a limited amount of protection

M.leprae - Prognosis

before treatment was available, diagnosis meant life long suffering and chronic pain and disfigurement, as well as being shunned by society; today, timely abx prevent infection from progressively destroying the body; antimicrobial treatment of advanced disease can eradicate infection but not repair damage from advanced disease

M.leprae - Prevention

avoid close contact with infected people who are untreated (no longer infectious once treated); keep distance form wild armadillos; early diagnosis and prompt drug therapy are critical to avoid complications; remains one of the most stigmatizing diseases; use standard infection control in a dental setting

Atypical Pneumonia Bacteria

distinguished from streptococcus, klebsiella, and haemophilus by clinical findings and lack of response to typical antibiotics used for classical pneumonia

Atypical Pneumonia

also called walking pneumonia; symptoms often milder, slower to develop (1-4 weeks after infection), and more persisted than those of typical pneumonia; person often not significantly ill, milder symptoms so can still walk around; symptoms commonly include headache, low grade fever, ear ache, sore throat; may become severe in patients with compromised respiratory/immune status

Causes of Atypical Pneumonia

mycoplasma pneumoniae (people under 40, most prevalent); chlamydia pneumoniae; legionella pneumophila (may be severe, most common in older adults, smokers, and immunocompromised)

Mycoplasma Pneumoniae

one of the smallest free living bacteria; too small to be visualized by light microscopy; lacks a cell wall; small genome with limited metabolic and biosynthetic capabilities; survival depends on tight adherence to human respiratory epithelium; escapes host immune response by intracellular localization

M.pneumoniae - Lack of Cell Wal

largely responsible for their cellular polymorphism; prevents staining by gram stain; naturally resistant to many antimicrobial agents; susceptible to dessication

M.pneumoniae - Main Virulence Factor

production of hydrogen peroxide; cytopathic effect to airway epithelium and cilia and responsible for persistent cough

M.pneumoniae - Infection

common cause of community acquired upper and lower respiratory tract disease in children and adults worldwide; easily transmitted person to person through respiratory droplets; incubation period is 2-3 weeks; causes a variety of clinical manifestations from no symptoms to mild cold like symptoms that can linger to severe atypical pneumonia

M.pneumoniae - Epidemiology

affects ages >5 to <40; occur throughout the year, but most common in summer and early fall; outbreaks often occur in households, schools, colleges, hospitals, nursing homes, military barracks and other crowded locations

M.pneumoniae - Signs and Symptoms

illness is typically mild with symptoms that get worse over a period of 1 to 4 weeks; most common sign is tracheobronchitis (chest cold); symptoms include fatigue, headache, sore throat, low grade fever, persistent/dry/nagging cough that lasts for weeks or months, chest discomfort with deep breathing/worsening of asthma symptoms

M.pneumoniae - Progression to Typical Pneumonia

happens in 10% of patients; symptoms include productive cough (produces mucus/sputum), fever, chills, shortness of breath, chest pain; children may also wheeze, vomit, and/or have diarrhea

M.pneumoniae - Treatment

most people recover from mild disease without treatment or diagnosis; pneumonia treated with antibiotics

M.pneumoniae - Prevention

there is no vaccine; infection is not protective against re-infection; protective methods are the same as for all respiratory infections

Legionella Pneumophila

non-encapsulated, motile, environmental gram negative bacilli; widespread in nature; reside in surface and drinking water; facultative intracellular parasite; most important atypical pneumonia pathogen in terms of disease severity; clinical manifestations are primarily respiratory

L.pneumophila - Facultative Intracellular Parasite

capable of living and reproducing either inside or outside cells; invade and replicate inside amoebae in the environment and macrophages in humans; intracellular lifestyle provides survival protection

L.pneumophila - Transmission

via inhalation of contaminated aerosols; person to person rare; infection begins in the lower respiratory tract where bacteria multiple intracellularly in alveolar macrophages; may be sporadic or epidemic (isolated event in community or as an outbreak in hospitals, resorts, schools)

L.pneumophila - Common Sources of Infection

hot tubs, cooling towers, hot water tanks, large plumbing systems, produce mist sprayers, decorative fountains

L.pneumophila - Legionnaire’s Disease

most severe type of atypical pneumonia; majority of people do not become ill; signs and symptoms appear 2-10 days after inhalation of the bacteria; often severe and may be fatal; 95% of patients require hospitalization, 10% patients die, 25% in a healthcare setting

L.pneumophila - Risk Factors

>50 years old, smoking history, lung disease, chronic illness, weakened immune systems

L.pneumophila - Signs and Symptoms

cough, shortness of breath, high fever, chills, headaches, muscle aches

Legionellosis

two different kinds of respiratory illnesses may result from infection; reasons for dichotomy remain unknown; legionnaire’s disease and pontiac fever

Legionellosis - Legionnaire’s Disease

most common type; disease varies in severity from mild illness that does not require hospitalization (walking pneumonia) to fatal multi-lobar pneumonia

Legionellosis - Pontiac Fever

less common and milder respiratory infection; symptoms resemble acute influenza (fever, headache, severe muscle aches); self limited infection, pneumonia does not develop, and symptoms go away without treatment in 2-5 days; named after a city in Michigan where the first epidemic was recognized

Legionnaire’s Disease - Epidemiology

not recognized until 1976 when a pneumonia epidemic struck american legion convention members (180 infected, 147 hospitalized, 29 died); 300% increased in diagnosed cases over the last 10 years; 6k-10k cases diagnosed per year in the U.S.; believed ot be vastly underdiagnosed with the true number of cases believed to be over 50k per year

L.pneumophila - Diagnosis and Treatment

confirmation of pneumonia by chest x ray/physical exam; urine test for legionella antigens; NAATs or culture of sputum or lung biopsy; analysis of blood ample for specific antibodies (serology); abx and/or hospitalization to prevent lung failure and death

L.pneumophila - Prevention

appropriate maintenance, cleaning, temperature regulation, and disinfection of water symptoms, hot tubs, spas, pools; avoidance of smoking to decrease susceptibility to disease

Eukarya Domain

branched off from archaea; true nucleus; unicellular and multicellular organisms; minority compared to prokaryotes but larger size

Eukaryotes

highly diverse domain; structurally and functionally complex; sexual and/or asexual reproduction; larger size and larger genome (multiple linear chromosomes); defined nucleus with membrane and membrane bound organelles

Endosymbiotic Theory

proposes how eukaryotes evolved from archaea; can be mitochondrial (engulfed nonphotosynthetic bacteria) or chloroplastal (engulfed photosynthetic bacteria)

Endosymbiotic Theory - Supporting Evidence

mitochondria and chloroplasts share size, 70s ribosomes, small/circular DNA/gene sequences, phospholipid bilayer surrounding membranes, and replication via binary fission with bacteria

Branches of Eukaryotes

fungi, plants, protists, animals

Branches of Eukaryotes - Fungi

unicellular and multicellular; chitin and glucan cell wall; produce oxygen and spores; sexually and asexually reproduce; can be pathogenic to humans; cell membranes contain ergosterols; grow slower than bacteria at a lower temp and pH; grow as yeast (microscopic), mold (macroscopic), or both (dimorphic)

Branches of Eukaryotes - Plant

most multicellular; cellulose cell wall; chloroplasts = photosynthetic; produce oxygen and seeds; sexually and asexually reproduce; no known human pathogens

Branches of Eukaryotes - Protists

most unicellular and or microscopic; sexually and asexually reproduce; photosynthetic algae and non-photosynthetic protozoans (pathogenic); can be pathogenic to humans

Branches of Eukaryotes - Animal

multicellular; lack cell wall; most use oxygen; move; sexually and asexually reproduce; can be pathogenic to humans

Ribosomes

non-membrane enclosed structure; protein factories; made of proteins and rRNA; 80s in cytoplasm and rough ER; 70s in mitochondria and chloroplasts

Ribosomes in Cytoplasm

produce cytosolic proteins

Ribosomes in ER

produce proteins destined for membrane insertion or secretion from the cell

Cytoskeleton

non-membrane enclosed structure; dynamic and responsive intracellular network of protein fibers; maintain shape and mechanically modify deformation; hold organelles in place; direct intracellular transport; involved in direct signaling pathways; coordinate cell division; facilitate movement

Membrane Bound Organelles

unique to eukaryotes (nucleus, smooth ER, rough ER, golgi, mitochondria, lysosome); structural and functional compartments; enclosed in lipid bilayers

Endomembrane System

endoplasmic reticulum, golgi apparatus, vesicles and vacuoles; large cell size and volume requires cellular transport system; series of membranous tubules, sacs, and flattened disks (cisternae) that synthesize many cell components and move materials within the cell

Nucleus

distinguishing feature of eukaryotes; essential role in all cellular activities (cell division, reproduction, heredity); enclosed by envelope; pores control traffic of materials

Nucleus - Nucleoplasm

houses DNA genome; multiple linear chromosomes; chromatin (complex of DNA + proteins/histones)

Nucleus - Nucleolus

dense region of rRNA biosynthesis; ribosome assembly begins

Mitosis

asexual reproduction; 1 parent cell divides into 2 genetically identical daughter cell clones → 1 division; more complex than binary fission (multiple chromosomes and organelles must be replicated/divided between daughter cells); development/growth, cell replacement, regeneration, asexual reproduction

Meiosis

sexual reproduction; consists of 2 cell division stages; 1 parent cell produces 4 genetically distinct gametes (homologous recombination); allows for genetic diversity and natural selection

Endoplasmic Reticulum

interconnected array of cisternae and tubules; originate from nuclear envelope; defined as rough or smooth

Rough ER

cisternae; studded with ribosomes; proteins produced, inserted into membrane, modified; bud off in vesicles - transported to golgi apparatus for further processing,the plasma membrane, the membrane of another organelle, or out of the cell

Smooth ER

tubules; no associated ribosomes; involved in biosynthesis of lipids, carbohydrate metabolism, and detoxification of toxic compounds

Golgi Apparatus

array of cisternae; enzymes modify lipids and proteins transported from the ER - add carbohydrates (glycolipids, glycoproteins, or proteoglycans); sorts and distributes final products (transport vesicles that pinch off, move to and fuse with cell/other membranes); cell surface significance of processed products

Golgi - Processed Products

distinguish types of cells; roles in cell recognition (other cells, viruses); serve as cell surface receptors

Vesicles

required for survival → transport, secrete, digest, and sequester materials; small, fluid filed, lipid bilayer enclosed, spherical sacs; membrane is same material as ER, golgi, plasma membrane, etc; self contained internal environment different vs cytosol; can fuse with/pinch off from any cellular membrane

Transport Vesicles

move materials within cell; shipping containers

Secretory Vesicles

store and traffic to cell surface for release; exocytosis (process of release to cell exterior; constutive or regulated)

Vacuoles

typically larger than vesicles, often used for storage; function dependent on cell type; osmotic regulation in fungi and protists; pH regulation, food storage, degradation

Degradative Vesicles

chemical rx chambers; lysosomes and peroxisomes

Lysosomes

cellular garbage disposals; digestive enzymes + low pH = break down particles (food, cellular debris, microorganisms, engulfed substances); compartmentalized (efficient digestion without collateral damage)

Peroxisomes

oxidative degradation; enzymatically degrade fats, amino acids, toxins; metabolize oxygen containing waste; protect cells from toxic oxygen intermediates

Mitochondria

double membrane, 70s ribosomes, circular chromosome → endosymbiosis ; primary function is to generate energy for the cell; makes ATP, amino acid, vitamins; carry out apoptosis; impact number of disease states, role in cancer and aging; number differs, active cells have a lot more

Plasma Membrane

phospholipid bilayer membrane on all cells; peripheral and integral proteins; fluid mosaic; selective barrier; contain sterols (cholesterol and ergosterol) for structural integrity

Endocytosis

plasma membrane folds around extracellular substances (invaginates); membrane pinches off; endosomes; import nutrients and substances inside the cell

Exocytosis

vesicles fuse with plasma membrane; contents may stay in membrane (proteins, lipids) or leave cell (wastes, chemicals)

Main Types of Endocytosis

pinocytosis (cell drinking up small, undissolved materials); receptor-mediated endocytosis (targeted uptake); phagocytosis (cell-eating large particles or other cells)

Receptor-Mediated Endocytosis

directed uptake; specific molecules (ligands) bind to specific membrane receptors on the cell surface (hormones, nutrients, viruses, bacteria)

Phagocytosis

performed by specialized immune cells (phagocytes); some protists; hydrolytic enzymes usually destroy contents of the phagolysosome; some pathogens have eveolved mechanisms for escaping the apparatus/neutralizing the enzymes; once the escape destruction, they replicate and cause disease

Glycocalyx

sticky, polysaccharide gel coating extracellular surface of PM; oligosaccharide domains of surface exposed glyocproteins and glycolipids (only found on cell surface); RER → golgi → secretory vesicles → delivered and fused into the PM; face of the cell (communicates with the extracellular world; roles in cell protection, interactions, adhesion, associates with other macromolecules (including pathogens and ECM)