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Clostridioides difficile (C. diff) Infection: MBIO 4823 Exam 5 Study Guide, Exams of Biology

This study guide provides a detailed overview of clostridioides difficile (c. Diff) infection, a common bacterial infection that can cause severe diarrhea and colitis. It covers the organism's characteristics, disease process, transmission, symptoms, diagnosis, and treatment. The guide includes numerous questions and answers, making it an excellent resource for students preparing for mbio 4823 exam 5.

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MBIO 4823 Exam 5 A
Fully Certified Latest Updated Exam Study Guide
2025/2026
What is C. diff known as and what is its full name? - ansClostridioides (Clostridium)
difficile. A new SUPERBUG of our times
What are two diseases associated with C. diff? - ansClosridium difficile- Associated Disease
(CDAD) and Pseudomembranous Colitis
Who reclassified C. diff? - ansPaul Lawson, Diane Citron, Kerin Tyrell, Sydney Finegold
What part of the GI tract does C. diff affect? - ansMainly found in Jejunum, where continued
digestion and absorption of monosaccharides, amino acids, fatty acid, water pH 4-5.
What is the gram reaction of all clostridial species? - ansAll clostridial species are Gram
positive
What kind of organism is C. diff? - ans*Obligate Anaerobe*
How many toxins does C. diff produce? - ansProduces *2 toxins*:
-*A-enterotoxin*
-*B-A-B cytotoxin*
Does C. diff form spores? - ans*Spore-former*
What is C. diff recognized as now? - ans-Now recognized as a *SUPERBUG*
-Many strains are susceptible to antibiotics but quickly becoming a major problem in
hospitals
When C. diff was recognized as a pathogen in 1960, what was it treated as? - ans-First
recognized as a pathogen when isolated from wounds, abscess, blood, and pleural fluid of
patients with a variety of illness- *but still not a problem*
What was C. diff discovered to cause in 1978? - ans-Discovered to *cause
pseudomembranous colitis (PMC).* The first association between C. diff and PMC
What else was discovered about patient symptoms in the year 1978? - ansThe same year *C.
difficile* was isolated from patients with the illness or experiencing postoperative *diarrhea*
What was discovered after antibiotics were used to treat C. diff? - ans*But it was not
anticipated that antibiotics used successfully to treat one bacterial infection could cause
another infection in the same patient! First instance of this.*
What is first step of the *disease process* with C. diff? - ans1. *C. difficile* vegetative cells
and spores are ingested:
-*vegetative cells are killed by stomach acid but spores survive*
What is the second step in C.diff disease that occurs upon exposure to bile acids? - ans2.
*Spores germinate in the small bowel* upon exposure to bile acids
How does the flagella support C. diff disease progression/movement to colon? - ans3.
*Movement to colon by flagella and polysaccharide capsule protects against phagocytosis*
What is the fourth step in C. diff disease progression? - ans4. Organisms *multiply in colon*
and adhere to epithelial cells
Describe the symptoms as C. diff cells *multiply in colon.* - ans-Local production of A & B
toxins
-Production of alpha-TNF, inflammation, increased vascular permeability, neutrophile and
monocyte recruitment
What is the fifth step of C. diff progression? - ans5. Opening of epithelial cell junctions and
cell apoptosis
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What is C. diff known as and what is its full name? - ansClostridioides (Clostridium) difficile. A new SUPERBUG of our times What are two diseases associated with C. diff? - ansClosridium difficile- Associated Disease (CDAD) and Pseudomembranous Colitis Who reclassified C. diff? - ansPaul Lawson, Diane Citron, Kerin Tyrell, Sydney Finegold What part of the GI tract does C. diff affect? - ansMainly found in Jejunum, where continued digestion and absorption of monosaccharides, amino acids, fatty acid, water pH 4-5. What is the gram reaction of all clostridial species? - ansAll clostridial species are Gram positive What kind of organism is C. diff? - ansObligate Anaerobe How many toxins does C. diff produce? - ansProduces 2 toxins:

  • A-enterotoxin
  • B-A-B cytotoxin Does C. diff form spores? - ansSpore-former What is C. diff recognized as now? - ans-Now recognized as a SUPERBUG
  • Many strains are susceptible to antibiotics but quickly becoming a major problem in hospitals When C. diff was recognized as a pathogen in 1960, what was it treated as? - ans-First recognized as a pathogen when isolated from wounds, abscess, blood, and pleural fluid of patients with a variety of illness- but still not a problem What was C. diff discovered to cause in 1978? - ans-Discovered to cause pseudomembranous colitis (PMC). The first association between C. diff and PMC What else was discovered about patient symptoms in the year 1978? - ansThe same year C. difficile was isolated from patients with the illness or experiencing postoperative diarrhea What was discovered after antibiotics were used to treat C. diff? - ansBut it was not anticipated that antibiotics used successfully to treat one bacterial infection could cause another infection in the same patient! First instance of this. What is first step of the disease process with C. diff? - ans1. C. difficile vegetative cells and spores are ingested:
  • vegetative cells are killed by stomach acid but spores survive What is the second step in C.diff disease that occurs upon exposure to bile acids? - ans2. Spores germinate in the small bowel upon exposure to bile acids How does the flagella support C. diff disease progression/movement to colon? - ans3. Movement to colon by flagella and polysaccharide capsule protects against phagocytosis What is the fourth step in C. diff disease progression? - ans4. Organisms multiply in colon and adhere to epithelial cells Describe the symptoms as C. diff cells multiply in colon. - ans-Local production of A & B toxins
  • Production of alpha-TNF, inflammation, increased vascular permeability, neutrophile and monocyte recruitment What is the fifth step of C. diff progression? - ans5. Opening of epithelial cell junctions and cell apoptosis

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After the sixth step involving hydrolytic enzymes, what occurs in C. diff progression? - ans6. Local production of hydrolytic enzymes: connective tissue degradation What occurs in the seventh (final step) of C. diff progression? - ans7. Colitis, pseudomembrane formation (dead tissue, fibrin, mucus phagocytes, DNA) and watery diarrhea Name a C. diff disease. - ansC. difficile- Associated Disease (CDAD) How is C. diff transmitted and by what route? - ansSpread from person to person contact. Fecal-oral route What conditions are the riskiest for C. difficile infection? - ansIn an environment where antibiotics cause a microbiota disruption and C. difficile that is resistant to that antibiotic has a selective advantage Describe how environments not containing antibiotics can create a risk for C. diff infection. - ansWhile a C. difficile that has antibiotic resistance has no advantage, if the microbiota is still disrupted, there is a risk for infection. What are three ways a patient that is negative for C. difficle can be be exposed to the organism and possible be infected? - ans- A nontoxigenic C. difficile can be asymptomically colonized in a host

  • Toxigenic C. difficile IgG response to Tox A can cause asymptomatic colonization
  • Toxigenic C. difficile with no IgG response to ToxA can cause symptomatic CDI What is pseudomembranous colitis and how does it allow overgrowth C. difficile? - ans- Severe ulceration of the colon, described 100 years ago and still rare until 1970s
  • Fatal within a few days
  • Inhibition of normal numerically dominant bacteria allow C. difficile to overgrow What facilitates adherence of C. diff to colonic epithelium? - ansGut mucosa Where does C. diff multiply? - ansColon How does C. diff move? - ansFlagellate facilitate C. difficile movement, a polysaccharide capsule discourages phagocytosis How do C. difficile spores germinate? - ansC. difficile spores germinate in the small bowel upon exposure to bile acids What occurs in the stomach to C. diff spores and vegetative cells that are ingested? - ansMost vegetative cells are killed in the stomach, but spores can survive in the acidic environment C. diff vegetative cells produce A and B toxins and hydrolytic enzymes; what do A and B toxins produce? - ans-Tumour necrosis factor-alpha and pro-inflammatory interleukins, increased vascular permeability, neutrophil and monocyte recruitment. What does local production of hydrolytic enzymes by C. diff lead to? - ans-Leads to connective tissue degradation, leading to colitis, pseudomembrane formation and watery diarrhea What does microscopy of C. diff infected stool show? - ansMicroscopy of the stool also shows presence of white blood cells in addition to red blood cells What can chronic symptoms lead to in C. diff cases? - ansChronic symptoms can lead to protein loss via the gut and to weight loss

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What effect do both toxins A and B have on G protein? - ansBoth toxins glucosylate (addition of glucose) a threonine residue on G protein Where would a threonine be located in a protein in the GTP form? - ans-In the GTP form the threonine is buried in the protein and inaccessible to the toxin What is the result of toxin activity on GTPase? - ans-Result: action of toxins reduced GTPase activity of the protein and increases release of GTP from GTP-bond form (glucosylated-GTP bound form has a lower affinity for GTP) Where are TcdA/TCDb Toxin genes located? - ans-Tcda/TcdB toxin genes* are located on PaLoc pathogenicity island present in all toxogenic strains What type of regulatory control is tcdC under? - anstcdC (down) What type of regulatory control is tcdR under? - anstcdR (up) What characteristic of tcdR activity in leads to expression of A and B toxins? - ans- Transcription and expression of tcdR is highest in early exponential phase leading to expression of A and B toxins When is tcdC expressed? - ans-When toxins build up to highest level, tcdC is expressed which counters tcdR decreasing the expression of the toxin What causes severe reactions in C. diff cases? - ansVery powerful toxins and small amounts can cause severe reactions What do bacteria get in return for all this energy expenditure? - ansNutrients How much percentage increase occurred in England and Wales? - ansA rise of 28 percent in just one year What population demographic does C. diff infection affect? - ansThe infection which particularly affects elderly people increased four times over since 2001 (1804 deaths were linked to the superbug) What do resistant spores in C. diff affected individuals lead to? - ansFailure to clear C. difficile and resotre stable, nonpathogenic flora What practices need to be implemented in C. diff cases? - ansTreatment coupled with improved clean practices within hospitals What is an enema? - ansAn enema is the procedure of introducing liquids into the rectum and colon via the anus What are the effects of motility of intestinal contents in C. diff cases? - ansLeakage of water into lumen - diarrhea 35,000 - ansBetween 1990 and 2003 cases of C diff rocketed. The cases increased from 1, cases to how many cases over this span? routine monitoring in feces for A & B toxins - ansin order to diagnose early and prevent C diff what precautions must be taken when someone experiences antibiotic associated diarrhea? Cytoskeletal protein Slide - ansClass 30 Slide 21 45,000 - ansHow many cases of C diff appeared in 2004 in >65 year olds? glucosylate - ansthis term describes an addition of glucose G protein - ansThis is an important protein involved in many cell processes that controls the polymerization and depolymerization of actin (pseudopodia etc) and cycles between 2 states: binding with GDP or GTP

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fecal bacteriotherapy (aka fecal microbiota transplantation FMT) - ansThis is a name for alternative therapy to replace resident flora using an enema containing dilute feces from a family member threonine residue - ansBoth C diff A-B toxins add glucose to this type of residue on G proteins. What is the residue called? vancomycin or metronidazole - answhat two antibiotics kill C diff but do not adversely affect normal flora? Where do Toxins A and B act (structurally)? - ans-A and B toxin act on GDP-bound form where the threonine residue is exposed that can by glucolyated (addition of glucose) What type of fecal bacteriotherapy has beens shown to improve C. diff symptoms? - ans- Fecal transplants that can induce solid bowel movements Name historical potential reasons for increased CDAD, incidence and severity. - ans-Changes in underlying host susceptibility

  • Changes in antimicrobial prescribing Name more recent potential reasons for increased CDAD, incidence and severity. - ans-New strain with increased virulence
  • CDT-binary toxin
  • Variations in TcdB activity
  • Changes in infection control practices What actin-specific toxin is produced by C. diff? - ansProduction of actin-specific ADP ribosyltransferase (binary toxin) by strains of C. diff What is PFGE? - ansDetection of Foodborne Diseases by Pulsed-field Gel Electrophoresis (PFGE) What is role of PulseNet? - ans-Detect food borne disease case clusters by PFGE
  • Early id of common source outbreaks
  • Separate outbreak associated cases from sporadic cases
  • Assist in rapidly ID'ing the source of outbreaks
  • Rapid and effective means of communication between public health labs Why was PulseNet developed? - ansFollowing large outbreak of E. coli O157:H7 in 1993, DNA fingerprinting by PFGE determined that the strain of E. coli in patients had same PFGE pattern found in hamburgers at food chains. CDC with APHL created PulseNet to allow clinicians to rapidly compare the PFGE patterns How does PulseNet work? - ans-PFGE done on disease causing bacteria and suspected food
  • PFGE patterns entered into national electronic database of DNA fingerprints
  • Certified participants can access
  • CDC and laboratorians look for clusters of patterns that are indistinguishable and it's reported to CDC team and PulseNet listserv What variations in Tcdb Activity contributed to hypervirulence of emerging strains of C. diff? - ans- The increased toxicity of TcdBhv (hypervirulent strains; more recent and more cytotoxic) was related to toxin's ability to enter cells more rapidly and at an earlier stage in endocytosis than normal TcdBHIST (historical strains)

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Name two similarities between Lyme disease and Syphilis. - ans-Both caused by spirochetes, although different genera

  • Both Lyme disease and Syphilis have multiple stages in their life cycle What media have syphilis cells been cultured on? - ans-Never cultured in the laboratory on artificial media --> tissue culture cells of cottontail rabbit epithelium Name a host for Syphilis. - ansHumans How is syphilis transmitted? - ansExtremely sensitive to environmental stress, transferred person-person by intimate sexual contact What other organism is syphilis often transferred with? - ans-Often transferred with N. gonorrhoeae but potentially much more serious Which ethnic group is the disease most prevalent in? - ans-Most prevalent among minority and ethnic population s: 60% higher in African-American than Caucasians What's another (historical) name for Syphilis? - ans-The "Great Pox" What physician infected himself with syphilis? - ansJohn Hunter Describe John Hunters experimental hypothesis. - ansAn infamous experiment
  • Hunter hypothesized that two diseases could not exist simultaneously in the same organ. Therefore, syphilis and gonorrhea were believed to be different symptoms of the same sexual illness
  • Had a theory that one disease was transferred by the discharges observed Describe John Hunter's experiment. - ans-Took discharge from male patient and transferred to glands of his own penis
  • Stabbed himself with a lancet several times
  • Squeezed cut open so liquid discharge could enter Describe the results of John Hunter's experiment. - ans-In a few days he reported a "tingling" in his penis followed by two chancres a few days later
  • Treated himself with mercury
  • Three months later got a skin rash, treated agin with massive dose of mercury, thought his symptoms disappeared for good.
  • Died 25 years later of syphilis and mercury poisoning What is a virulence factor of Syphilis? - ans-Ability to transit epithelia to invade body What do the ends of bacteria attach to that joins endothelial cells? - ans-Ends of the bacteria attach to the hyaluronic-acid-containing extracellular matrix that joins capillary endothelial cells What type of motility does Syphilis have and what does it enable it to do? - ansCorkscrew motility, cross tissue layers and enter and exit blood stream How are fetuses at risk for syphilis? - ansSyphilis has ability to cross the placenta Name three stages of progression of syphilis. - ans1. Primary
  1. Secondary *Latency
  2. Tertiary Class 32 Slide 11

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Where does infection occur in primary syphilis? - ansT. pallidum cannot pass through unbroken skin. Infection probably occurs via small tiny breaks in the epidermal layer caused during sexual activity Where does syphilis affect males? - ansMale: penis Where does syphilis affect females? - ansFemale: vagina, cervix, and surrounding regions If syphilis becomes extra genital, what areas does it affect? - ansUsually oral and anal regions What type of syphilis occurs when a fetus is infected? - ansCross placenta and infects fetus- Congenital syphilis What are the first symptoms of syphilis? - ansFirst symptoms: rhinitis (irritation and inflammation of the nose) and then rash Name symptoms of chronic syphilis infection. - ansTeeth and bone malformations, blindness, deafness, cardiovascular syphilis are common in untreated infants who survive. Where does T. pallidum multiply and what characteristic lesion is formed? - ansT. pallidum multiplies at the site of entry and a characteristic lesion (chancre) formed within 2 weeks to 2 months Name areas that T. pallidum can "hide". - ansMaybe hidden-on scalp under the hair, vagina, anus or mouth What are the spirochetes actively doing, relate it to pathogenicity? - ansSpirochetes actively multiplying, infectious What happens after a few weeks that provides a false sense of relief for patient? - ansChancre disappears after a few weeks and heals spontaneously (bacteria migrating away from the site) List the progression of Secondary syphilis (1-3 months) - ans-Bacteria penetrate mucosal membranes and enter bloodstream

  • Bacteria spread to mucous membranes, eyes, joints, bones or CNS
  • Body mounts an immune response What common viral symptoms does the body exhibit? - ansFlu like symptoms: sore throat, headache, fever and swollen lymph glands Name the Key Feature of Secondary Syphilis. - ansKey Feature: hypersensitivity reaction, rash that covers entire body-highly contagious Compare the size of "great pox" to small pox. - ansThe "great pox", larger than small pox. (Pus filled marks) What phase do patients enter clinically after rash and symptoms gradually resolve spontaneously? - ansInactive or latent phase
  • Patients may think he/she is cured
  • May not be true but not in all cases Describe the immune response of Tertiary (Late) Syphilis (3-30 years). - ans-Small number of cases progress to this stage, range of symptoms from mild to fatal infections with relatively low numbers of bacteria
  • Immune response-Chronic inflammation: destruction of virtually any organ or tissue. Disabling fatigue, disfiguring skin lesions, bone malformation (archeological information) When does syphilis turn into a fatal infection? - ansFatal infections if vital systems/organs are affected; cardiovascular and CNS

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  • The victims of the study included numerous men who died of syphilis, wives who contracted the disease, and children born with congenital syphilis What did the Tuskegee Syphilis Study lead to? - ansArguably the most infamous biomedical research study that led Institutional Review Boards for protection of human subjects What are some Other Tests in D.C? - ansAt one time (outlawed 9/11/08), couples needed to have certified blood test for VDRL syphilis Have some parts of the world eradicated or almost eradicated this disease? - ansYes; controlled by safe sex. *Problem with prostitution among drug users that causes a viscous cycle of infection What is a chancre? - ans-Replication at the site of entry triggers massive leukocyte infiltration, blood vessel damage, tissue necrosis How are many cases of primary and secondary syphilis spontaneously resolved? - ansBy the adaptive system:
  • CD8+ cytotoxic T lymphocytes
  • cytokine production (alpha interferon, interleukins)
  • degraded treponemes are found in phagolysosome But can proceed to tertiary stage that may last for years or decades What occurs to the rabbit model infected with syphilis? - ansLong lasting immunity does not develop until about three months post infection and fails altogether if interrupted by antibiotic therapy Why does acquired immunity develop so slowly and why is the pathogen not eliminated? - ansPoor immunogenicity of and immune evasion may be the answer* What do ultrastructure studies show of T pallidum? - ansT. pallidum is largely devoid of membrane associated proteins
  • These may be involved in attachment and invasion of the host and may be the target of the adaptive immune response What do "persistent treponemes" harvested from rabbits show? - ansThat they are less susceptible to macrophages What is suggested to account for "persisters"? - ansSuggested that subpopulations of antigenic variants account for these "persisters" Who is often blamed for origin for bringing syphilis to Europe? - ansColumbus and his crew
  • Skeletons from archaeological sites in the U.S. and Ecuador ranging in the age from 400- 6,000 years Why did Syphilis spread in particular in Europe? - ansEurope constantly at War, soldiers in particular could spread this disease because of constant movements to different countries Which location in English location showed evidence of skeletal syphilitic lesions? - ansEuropean evidence, especially syphilitic lesions in skeletons from a 14th century English monastery
  • many new findings in Europe show tell tale signs of syphilis: 70 years before the voyage of Columbus What are current thoughts of the origin of Syphilis? - ans-Probably acquired from animals in Africa; resembles present day treponeme infections of baboons
  • Treponemes mutated and crossed species barrier to - Yaws a skin disease

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Treponema pallidum subsp. pertenue - ans-a tropical (topical) infection of the skin, bones, and joints caused by the spirochete bacterium Map showing human migration routes beginning about 100,000 years ago of the globe - ansClass 32, Slide 44 Where was Yaws maintained? - ansWarm-moist areas of South America; as populations migrated to northern regions and wore more clothing, Treponemes mutated again Name modes of transmission for treponemes. - ans1. Migrated to mouth and throat via saliva on drinking vessels etc;

  1. 15th and 16th century saw urbanization and sexual liberties

  2. Combined with more clothing in cold climates forcing pathogens to find new ways to transfer between individuals Many more chances for the organism to spread How did treponemes take advantage of more clothing? - ansMutated from a skin to a venereal disease What is gram reaction and morphology for C. difficile? - ansGram positive, rod How is C. diff transmitted? - ansFecal-oral What are C. diff virulence factors? - ansSpres, A&B toxins What are disease symptoms and treatments for C. diff? - ans-antibiotic associated diarrhea

  • pseduomembraneous colitis
  • vancomycin/metronidozole What is gram reaction and morphology for Y. pestis? - ans-Gram negtaive
  • coccobacillus
  • dipolar staining What is a mode of transmission for Y. pesitis? - ansFlea-rat interaction lifecycle What are virulence factors for Y. pestis? - ans-Plasmids
  • Yops
  • LPS
  • Capsule What are diseases symptoms and treatment for Y. pestis? - ans-Bubonic plague
  • Buboes
  • Septic Shock
  • Pneumonic plauge Gram reaction for Y. Enterocolitica and Y. pseudotuberculosis? - ansNone given Mode of transmission for Y. Enterocolitica and Y. pseudotuberculosis? - ansFood-water Not insect Virulence factors Y. Enterocolitica and Y. pseudotuberculosis? - ans-Adhesins
  • Invasins
  • Causes inflammation
  • Cross membranes via M cells Disease symptoms/ treatment for Y. Enterocolitica and Y. pseudotuberculosis? - ansGastroenteritis Is Treponema pallidum continuing to evolve? - ansEarly reports from Europe 1400s:
  • boils that stood out like acorns from where filthy stinking matter was issued

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In theory syphilis could be eradicated but what would impede this? - ansHuman behavior cannot be controlled but through safe sex practices may be able to reduce the incidence What is Mycobacterium tuberculosis known as? - ans-The People's Plague

  • One of histories most feared killers
  • known as consumption b/c it seemed to consume people from within What classification does tuberculosis? - ansOld-New or Reemerging Disease Gram reaction, morphology and growth of Mycobacterium tuberculosis? - ans-Aerobic, very slow growth
  • Gr. +ve type cell wall but Gram stain not useful
  • High content of mycolic acids (lipids 10% cell weight)- leads to term "acid-fast" as a robust method of staining
  • Highly contagious, aerosol spread Note that M. tuberculosis does not require a large number for multiplicity of infection How quick is M. tuberculosis division time compared to E. coli? - ansVery slow --> M. tuberculosis divides every 16-20 hours while E. coli can divide in 20 minutes What does acid fast staining of M. tuberculosis produce? - ansDiagnostic red bacilli Where did M. tuberculosis evolve from? - ans-Evolved from a disease of cattle 8000- 4000 BC, herdsmen: probably from the soil organism M. bovis What were found in Early Egyptian mummies in relation with M. tuberculosis? - ans- Characteristic bone malformations but not evidence of lung damage Where and how was the earliest known human TB found? - ansSubmerged off the coast of Israel in 9000 year old skeleton What did genomic studies of M. tuberculosis complex reveal? - ansIndicate a more ancient origin of this group of closely related species than had previously been believed Where was a possible early progenitor present in for M. tuberculosis? - ans-East Africa as early as b 3 million years ago
  • Also observation of non-specific lesions consistent with tuberculosis found in a 500, year old skeleton of Homo erectus What is significant of M. tuberculosis co-evolution with human host? - ans-M. tuberculosis appears to have undergone long-term co-evolution with its human host well before the development of agriculture and domestication although these contribute to increased transmission.
  • May indicate the long-term co-existence of host and pahtogen
  • Believed to have co-evolved with its host over millenia supported by skeletal evidence What can DNA evidence be aided by? How do biomarkers aid in our understanding of nature? (M. tuberculosis) - ans-chemical markers
  • of the nature of prehistoric tuberculosis and the host/pathogen relationship M. tuberculosis is top (1) ____killer along with(2) _____ and(3) ______ - ans1. three
  1. HIV
  2. Malaria
  • synergistic with HICx 800 chance of contracting TB

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Why are more people in developed world susceptible to contract TB? - ans-Immune systems are more likely to be compromised due to higher exposure to immunosupporessive drugs, substance abuse, or AIDS Is distribution of TB uniform across globe? - ansNo, more population in many Asian and African countries test positive for TB while less of US population test positive Over next decade ______ will _____________________ - ans-30 million will die worldwide (from TB) Name a multiple drug resistant TB. - ansMDR-TB Name an extremely drug resistant TB. - ansXDR-TB Why is drug resistance so high with TB? (Massive outbreaks in Russian prisons) - ans-Lack of new anti-TB drugs

  • Streptomycin (old drug) imported from developing countries
  • Young Dr's couldn't diagnose TB What are symptoms of TB? - ans-highly contagious, 3 organisms can cause this:
  • Fever, coughing, bloody sputum, weight loss, malaise, progressive and irreversible lung destruction, fatal progresses slowly (yrs), more Why do all cells have MHC complexes? - ansFor Host recognition Where and how are protein antigens transported across ER membrane? - ansProtein antigens degraded by the phagosome in the cytoplasm are transported across the ER membrane formed by TAP (transporters associated with antigen processing) What is MHC-I protein held in place by? - ans-By a chaperone until the peptide is bound After chaperone is released, the protein complex is transported to cell surface to inter act with_______? - ansChaperone is released and the protein complex is transported to the cell surface and interacts with the T-cell receptors (TCRs) What do perforins do? - ansMake holes in cell membrane and initiates apoptosis
  • Kills infected host cells What are intracellular pathogens? - ansAntigens processed from an internal source- cytoplasm Interaction with Cytotoxic Lymphocytes (T cells) - ansClass 34 Slide 5 What are other immune cells involved in Cytotoxic lymphocytes? - ans-B lymphocytes- produce antibodies to extracellular pathogens
  • Memory plasma cells, that can quickly divide and produce the pre-programmed antibodies from a previous infection How is Mycobacterium tuberculosis able to overcome these immuno mechanisms? - ans- They actively infect macrophages and mostly survive the destructive activates normally found in the phagolysosome The T cell response is not initiated and so cytokines, IFN, gamma TNF are not produced --> These normally recruit more macrophages to the site of infection and increase phagocytosis and inflammation How does Mycobacterium tuberculosis enter the host? - ansAerosols in airway

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What was introduced after streptomycin resistant TB strains developed? - ansRifampin an inhibitor of RNA What is an MDT and what drug cocktail was used in TB treatment next? - ans-MDT (Multiple drug therapy)

  • Rifampin and isoniazid (blocks synthesis of mycolic acids) After 9 months of the MDT therapy for TB, what was shown? - ansPatients were not completing the course of the drugs, which lead to drug resistance of rifampin- isoniazidcomplex that was most effective against TB. What is MDR-TB? - ansMultiple drug resistant TB
  • resistant to 2 or more of anti-TB drugs (isoniazid and rifampin) Which strain of TB emerged in NY that was resistant to almost all of the antibiotics used? - ansW strain
  • Highly virulent and infectious
  • Drastic measures were taken: a) isolation b) surgical removal of lung tissue c) use of experimental drugs 74% mortality What is XDR-TB? - ansExtremely drug resistant TB
  • resistant to isoniazid and rifampin and at least 3 second line drugs These strains are a major problem and predicted to kill millions What is TDR-TB? - ansTotally drug resistant TB
  • New deadly strain discovered in India What is the strain used for TB vaccine? - ansAvirulent M.bovis strain BCG (Bacillus Calmette-Guerin)
  • French scientists transferred 231 generations over 13 years to weaken this "attenuated" disease producing the BCG species What is an attenuated vaccine? - ans-Is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable (or "live") What does attenuation do? - ansTakes an infectious agent and alters it to so that it becomes harmless or less virulent What were the results of this vaccine when first implemented? - ansNot good, out of 249 babies 79 died
  • Not from BCG. They died from contamination from live M. tuberculosis stored in the same incubator
  • restricted use for decades b/c of public concerns Why is BCG not generally recommended for use in the U.S - ansBecause of the low risk of infection with Mycobacterium tuberculosis, the variable effectiveness and the vaccines potential interference with tuberculin skin test reactivity What recent discovery of bacteriophages with TB vaccines could change the vaccination? - ansRecent discovery of bacteriophages that convert avirulent vaccine strains to potential deadly pathogen

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What are some possible future vaccines against TB? - ans-Introduce genes for effective antigens from a number of bacterial species for a multipurpose vaccine

  • Use of psoralen and UV treatment, cross links DNA and prevents DNA synthesis while allowing protein synthesis and metabolism. Organisms do not multiply but remain alive and produce antigens What is regarded as the most advanced of a new generation of preventive TB vaccines under development - ansThe new MVA85a What is DOTS? - ansDirect Observational Therapy Short course
  • healthcare workers physically watch patients swallow their daily dose of anti-TB drugs What are phenotypic characteristics for TB (Gram etc;)? - ans How does M. tuberculosis avoid the normal immune system? - ans How does the body attempt to contain the TB infection? - ans What is latency and persistence in TB? - ans What are vaccines developed and their effectiveness against TB? - ans What is Chlamydia trachomatis known as? - ansthe silent destroyer What is gram reaction and morphology for chlamydia trachomatis? - ansSmall Gr - ve rods What type of pathogen is chlamydia trachomatis? - ansObligate intracellular pathogen What is the characteristic known of the peptidoglycan for chlamydia trachomatis? - ansNo "detectable peptidoglycan What are serovars and how are they associated with chlamydia trachomatis? - ansMany serovars (strains) associated with specific diseases What is known about the genome for chlamydia trachomatis? - ansReduced genome size 1000 kbp (E. coli 4600) What is unusual about the life cycle of chlamydia trachomatis? - ansUnusual 2 stage life cycle Can chlamydia trachomatis live outside the body? - ansChlamydia cannot live outside the body (toilet seats, bed linens: no) What is the most common STD? - ansCervical infection What is Trachoma and what does it cause? - ansChronic disease (North and sub-Sahara Africa, Middle East, Asia and South America) Causes blindness to 6 million 150 million in need of treatment Leading cause of preventable blindness Where are chlamydial diseases found? - ansOn college campuses and rich neighborhoods Who is at risk for chlamydia? - ans-Sexually active young people are at a higher risk of getting chlamydia
  • Gay, bisexual, and other men who have sex with men are also at risk since chlamydia can be spread through oral and anal sex
  • Pregnant women
  • Women sexually active under the age of 25 years What is cervicitis? - ansInflammation of the tissues of the cervix
  • Pelvic inflammatory disease (PID)