Microbiology-For Exam 3

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chemotherapy

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the treatment of infectious diseases with chemicals or antibiotics that are inhibitory or lethal to the infecting agents

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selective toxicity

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the property of some antimicrobial agents to be toxic for a microorganism and nontoxic for the host

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antibiotic

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a low molecular weight chemical agent produced by one organism that is harmful to other organisms

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antibacterial spectrum

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range of activity of an antibacterial agent

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broad spectrum

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the drug can inhibit a wide variety of gram positive and gram negative bacteria

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bactericidal

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the drug KILLS the bacterial cell

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bacteriostatic

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the drug prevents the growth of microorganisms. The drugs must be used for a sufficient time to allow the host's own defenses, such as phagocytosis and antibodies, to destroy the organism

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major mechanisms of antibacterial agents

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1. inhibition of cell wall sythesis
2. inhibition of protein synthesis
3. alteration of cell membranes
4. inhibition of nucleic acid synthesis
5. antimetabolites

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How does inhibition of cell wall synthesis work?

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cell wall acting antibacterial agents interfere with the synthesis of intact peptidoglycan, as a result, cell wall weakened undergoes lysis

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Why does cell well synthesis inhibition not affect mammals?

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because mammalian cell walls do not have peptidoglycan

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How do antibiotics that bind to 30s subunit work?

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1. block binding of fmet tRNA to the ribosome, preventing initiation complexes
2.prevent attachment of tRNA to binding site, preventing addition of amino acids to polypeptide chain
3. cause misreading of codons on mRNA
4. lead to the formation of nonfunctional proteins

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How do antibiotics that bind to 50s subunit work?

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1. chloramphenicol blocks the action of peptidyl transferase, preventing peptide bond formation
3. erythromycin blocks translocation step, preventing release of tRNA after peptide bond formation

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Chloramphenicol

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blocks action of peptidyl transferase, preventing peptide bond formation in growing polypeptide chain

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erythromycin

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blocks the translocation step, preventing the release of tRNA after the peptide bond formation

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Mechanisms of drug resistance:

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1. develop an altered metabolic pathway, bypasses reaction inhibited by drug
2. produce enzyme that destroys drug
3. may change permeability to drug
4. develops altered structural target for drug

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antibiotic sensitivity tests

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valuable for selecting chemotherapeutic agents active against the infecting organism

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Factors when selecting a drug

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pharmokinetic properties of the drug, drug toxicity, site of infection, patient's general medical status (pregnancy, renal/hepatic dysfunction)

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Fungus

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yeasts, mold, mushrooms

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General Properties of fungi

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multicellular eukaryotes, except yeast are unicellular
chemoheterotrophs-organic compounds
-sexual and asexual reproductive spores
-two basic forms-yeast and molds

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hyphae

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tubular, branching filaments of fungal cells, the mold form of growth

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mycelium

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mass of branching hyphae, typically found in molds

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yeasts

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unicellular, spherical to ellipsoid fungal cells that reproduce by budding

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septum

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a cross wall in a hyphae

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dimorphic fungi

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fungi that have two growth forms, such as a mold and yeast, which develop under different growth conditions

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pseduohyphae

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elongated chains of buds or blastoconidia

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conidiospore

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an asexual spore produced in a chain from a conidiophore

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conidiophore

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an areial hyphae bearing conidiospores

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athroconidia

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conidiospores that result from the fragmentation of hyphal cells

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blastoconidia

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conidial formation thorugh a budding process

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ectothrix

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presence of arthroconidia outside the hair shaft

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endothrix

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arthroconidia found within the hair shaft

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morphologic forms of fungus

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yeast-single cell
mold-filamentous

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coenocytic hyphae

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molds in which hyphae contain no septa and appear as long, continuous cells with many nuclei

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vegetative (substrate) hyphae

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hyphae that penetrate the supporting medium and absorb nutrients

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aerial hyphae

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project above the surface of the medium on which the mold is growing, usually bear the reproductive structures of the mold

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budding

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parent cells forms a protuberance on its outer surface, bud elongates and parent's cell nucleus divides and one nucleus migrates into bud, cell wall material laid down, bud breaks off

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yeast colonies

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usually soft, opaque, 1-3 mm in size, cream colored

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dimorphic fungi in soil or below 35 C

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produces vegetative and aerial hyphae, spores formed are the infective particle

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dimorphic fungi in tissues or above 35 C

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fungus is yeastlike and reproduces by budding

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spores differ from bacterial endospores?

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1. reproductive spores (detach from parent and form new spore)
2. can survive for extended periods in dry or hot environments, most DO NOT exhibit the extreme tolerance and longevity of bacterial endospores

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Asexual spores

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produced by an individual fungus through mitosis and subsequent cell division, no fusion of nuclei of cells, become organisms identical to parent

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medically important fungi produce two major types of asexual spores?

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conidia and sporangiospores

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arthroconidia

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formed by the fragmentation of septae hyphae into single, slightly thickened cells

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chlamydospore

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thick walled spore formed by rounding and enlargement within a hyphal segment

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sporangiospores

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formed within a sac (sporangium) at the end of an aerial hyphae called a sporangiophore, may contain hundreds of sporangiospores

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sexual reproduction

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sexual spores result from the fusion of nuclei from two opposite mating strains of the same species of fungus, progeny show characteristics of both parents

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Fungi produce sexual spores...

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less often than asexual spores

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Fungi pH

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5.0, slightly acidic, skin 3-5

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Molds grow under

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aerobic conditions

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Yeast are...

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facultative anaerobes

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Fungi more resistant to osmotic pressure changes than bacteria...

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can grow in relatively high sugar or salt concentration

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keratin

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protein found in hair, skin, and nails

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predisposing factors to fungal infection

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1. prolonged administration of broad spectrum antibiotics
2. exposure to a large number of spores

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superficial mycoses

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limited to outermost layers of stratum corneum of skin and along hair shafts, do not elicit a cellular response from host b/c they colonize non living tissue

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cutaneous mycoses

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generally restricted to keratinized layers of skin and its appendages
-vast cellular immune responses provoked

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Most important cause of cutaneous mycoses?

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Dermatophytes-infection transmitted from human to human or human to animal by direct contact RINGWORM

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subcutaneous mycoses

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-involve dermis, subq tissues, muscles, fascia and sometimes bone
-usually granulamatous lesions that expand slowly from site of implantation

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Subcutaneous mycoses usually?

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saphrophytic that live on soil and on vegetation, infection usually occurs by direct implantation of spores or mycelial fragments into a puncture wound in the skin

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systemic mycoses

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fungal infections deep within the body
usually caused by dimorphic fungi that live in the soil

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Route of transmission for systemic mycoses?

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Inhalation-disease usually starts in lungs and then spreads through body

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hypersensitivity disease

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allergies, spores constantly present in nature elicit allergic reaction in some individuals and animals

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mycotoxicoses

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secondary metabolites and their effects are not dependent on fungal infection or viability

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aflatoxins

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hepatotoxins, produced by aspergillis spp. growing on peanuts and various grainds

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ergot poisoning

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caused by alkaloids growing on cereal grains and grasses, have oxytocic and vasoconstrictive effects

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mycetismus

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mycotoxins produced by mushrooms that can result in hallucenogenic, serious/fatal mushroom poisoning

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amanita phalloides

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cause 90% of all deaths by mushrooms, "death cap", produce heat stable cyclic polypeptides that are toxic to kidneys and liver

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adolf mayer

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dutch chemist, 1886 showed that tobacco mosaic disease could be transmitted from a diseased plant to a healthy plant

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dmitri iwanowski

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russian bacteriologis, 1892 attempted to est. cause of tobacco mosaic disease by filtering the sap of diseased tobacco plants through a porcelain filter that was designed to retain bacteria, passed through filter but still assumed from a bacterium

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martinus beijerinck

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dutch botanist, 1899, determined that agent causing tobacco mosaic disease was different from that of a bacterium

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wendell m stanley

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american chemist, 1935, isolated the tobacco mosaic virus making possible for the first time to carry out chemical and structural studies on a purified virus

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obligate intracellular parasites

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viruses, able to multiply only inside living cells by using the synthesizing machinery of the cell

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Why give antibiotics for viruses?

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viruses are not sensitive to antibiotics but they are given for possible secondary bacterial infection

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host range

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animal species and the spectrum of host cells the virus can infect

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Host range determined by...

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-attachment sites
-ability to provide cellular factors required for viral multiplication

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Virus consists of..

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nucleic acid surround by capsid (protein coat)

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reverse transcriptase

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RNA dependent DNA polymerase, transcribes the information in the viral RNA into a DNA intermediate

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envelope

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surrounds the nucleocapsid, composed of lipid bilayer with proteins, usually glycoproteins, embedded in it

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spikes

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attach the virus to the host cell membranes

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icosadhedral (cubic) virions

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20 equilateral, triangular faces, 12 corners, 30 edges
-most efficient arrangement for capsomeres in a closed shell b/c uses smallest number of subunits to build a shell
-may be naked or enveloped

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helical virions

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-resemble long rods
-length determined by nucleic acid, width by size and packing of protein subunits

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complex virions

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-poxviruses
-complex in structure, several parts with diff. shapes/symmetries

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positive sense RNA genome

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translation to polypeptides

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negative sense RNA genome

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transcription to mRNA then translation to polypeptides

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Grouped into families based on:

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1. nucleic acid type
2. strategy for replication
3. morphology

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DNA virus families (9)

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asfar-, pox-, irido-, parvo-, circo-, hepadna-, herpes-, papillo-, adeno-,

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RNA virus families (16)

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reo-, bima-, orthomyxo-, rhabdo-, boma-, paramyxo-, bunya-, filo-, corona-, arteri-, toga-, flavi-, picoma-, astro-, calici-, retro-

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Embryonated eggs for viral replicaton

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hole drilled in shell and virus injected into fluid of egg most appropriate for growth, hole covered with parafilm or scotch tape and incubated

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Types of fluid in egg

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yolk, amniotic, allantoic

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Viral growth in egg may result in

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-death of embryo
-paralysis of embryo
-stunted growth of embryo
-formation of pock lesions on egg membranes

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pock lesions

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necrotic lesion

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What is a cell culture?

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tissue removed from lab animal, grown, watched for viruses to deteriorate monolayer

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cell culture medium provides

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osmotic pressure, nutrients, and growth factors

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Cells in culture produce?

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glycoprotein like material that permit adherence to glass in monolayer

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Two morphological forms of viral capsids?

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icosahedral and helical

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Steps of Virus Replication

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1.adsorption (attachment)
2.penetration (engulfment)
3. uncoating
4. replication
5. assembly
6. release

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adsorption(attachment)

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attach to complementary receptor sites on host cell
-host cell receptors usually proteins or glycoproteins

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penetration (engulfment)

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virus particle taken into cell
-receptor mediated endocytosis or surface fusion

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receptor mediated endocytosis

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hose cell enfolds the virion into a fold of plasma membrane forming a vesicle

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surface fusion

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the envelop of some enveloped viruses contain fusion proteins, proteins promote fusion between the envelope and the plasma membrane with subsequent release of the capsid into the cells cytoplasm

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uncoating

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-physical seperation of viral nucleic acid from the outer structural components
-done by lysosomal enzymes of host cells

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replication of + sense RNA genome

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via a - sense intermediate template called replicative template

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replication of - sense RNA genome

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-complementary to mRNA must be transcribed into mRNA before translation can take place

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Naked virus release

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progeny are released following lysis of the host cell

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Enveloped virus release

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acquire envelope by budding through host cell plasma membrane

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interference with dna gyrase

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quinolones, nalidixic acid

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interference with DNA synthesis by blocking folic acid production

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sulfonamides

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inhibition of cell wall synthesis

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penicillin, vancomycin

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inhibition of protein synthesis

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neomycin, doxycycline

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inhibition of protein synthesis at 50 s subunit

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chloramphenicol, tylosin, clindamycin

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inhibition of cell membrane function

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polymyxin