Lecture #29 - Lecture 29 Bacterial Toxins Bacterial Toxins...

Info icon This preview shows pages 1–5. Sign up to view the full content.

View Full Document Right Arrow Icon
11/19/2007 1 Lecture 29 Bacterial Toxins Horizontal Transfer of Pathogenesis genes Host Detection by Bacterial Pathogens BBOM 11e Sec. 4.9, 21.9 – 21.12, 8.10, 19.21, 10.10, 29.8, 28.5, 20.7 – 20.9, 20.12, 30.5 Antibiotics and Antibiotic Resistance Bacterial Toxins Endotoxins (Sections 4.9, 21.12) Lipopolysaccharides. Lipid A is the toxic component, while the polysaccharide increases water solubility. Cause a massive immune response, fever. Can be fatal in large amounts. Exotoxins (Sections 21.10, 21.11) Enzymes, exported from bacteria, enter host cells, and catalyze specific biochemical reactions. First described exotoxin: Diphtheria toxin. Cornyebacterium diphtheriae does not leave the site of infection yet causes systemic symptoms Emil Roux in 1880's leave the site of infection, yet causes systemic symptoms. Emil Roux, in 1880 s, postulated that the bacteria must release a toxin that spreads systemically. Roux grew a broth culture of the bacterium, removed the bacteria by filtration, and injected the cell free culture into mice, causing the disease symptoms. Birth of “Molecular Koch’s Postulates.”
Image of page 1

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
11/19/2007 2 Endotoxin, also known as Lipopolysaccharide (Fig. 4.34) Cytolytic toxins Bind to host cells and induce lysis. Often tested using animal red blood cells (because lysis is easy to detect on solid agar medium), and are therefore often called “hemolysins”, but natural substrate is generally other cell types. cytoplasmic contents released
Image of page 2
11/19/2007 3 The A domain of Diphtheria toxin covalently modifies EF 2, blocking protein synthesis. Exported from cytoplasm with cleavage of signal sequence. Two cysteine residues are covalently linked, forming a disulfide bond. Peptide backbone cleaved, so that two halves are joined only by the disulfide bond. Binds to host cell. “A” subunit is inserted through host membrane. Disulfide bond is cleaved, freeing A domain.
Image of page 3

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
11/19/2007 4 | | | | CO CO CO CO | | Extracellularly | | CH-CH2-SH + HS-CH2-CH ---------------> CH-CH2-S-S-CH2-CH | | <--------------- | | NH NH Intracellularly NH NH | | | | Cysteine Cysteine Disulfide bonds between two cysteine residues are formed outside the cell and are broken in the bacterial and host cytoplasms. Structure of NAD + . Toxin inhibits protein synthesis by inactivating Elongation Factor 2. Covalently modifies EF2. Uses NAD to donate ADP ribose to EF2, releasing nicotinamide. “ADP ribosylation” is a common reaction for toxins. Pseudomonas aeruginosa P. aeruginosa , unlike many pathogens, extremely versatile, colonizing many nonhuman niches. “Opportunistic” pathogen. Usually does not cause clinical problems, but can infect: burn patients immunocompromised individuals lung tissue of CF patients indwelling catheters. Causes “nosocomial” infections (infections obtained at a hospital). Exotoxin A Precursor Exotoxin A. Mode of action: ADP-ribosylation of EF- 2. Catalytic domain evolutionarily related to diphtheria toxin.
Image of page 4
Image of page 5
This is the end of the preview. Sign up to access the rest of the document.

{[ snackBarMessage ]}

What students are saying

  • Left Quote Icon

    As a current student on this bumpy collegiate pathway, I stumbled upon Course Hero, where I can find study resources for nearly all my courses, get online help from tutors 24/7, and even share my old projects, papers, and lecture notes with other students.

    Student Picture

    Kiran Temple University Fox School of Business ‘17, Course Hero Intern

  • Left Quote Icon

    I cannot even describe how much Course Hero helped me this summer. It’s truly become something I can always rely on and help me. In the end, I was not only able to survive summer classes, but I was able to thrive thanks to Course Hero.

    Student Picture

    Dana University of Pennsylvania ‘17, Course Hero Intern

  • Left Quote Icon

    The ability to access any university’s resources through Course Hero proved invaluable in my case. I was behind on Tulane coursework and actually used UCLA’s materials to help me move forward and get everything together on time.

    Student Picture

    Jill Tulane University ‘16, Course Hero Intern