Bio 207 Exam 3

General Host Defenses (first line of defense)

• Skin & Mucosal Surfaces

  • organism must penetrate, adhere, grow

    • there is tissue specificity for most infectious agents

    • tight junctions in epithelial tissue seal off "inside"

    • mucus limits direct access to epithelial cells

  • breaks in epithelium allow microbes to bypass these barriers

• Normal Flora

  • young are more susceptible before stable adult flora develops

  • diet, drugs can alter normal flora

• Antimicrobial Secretions

  • lysozyme & other enzymes kill bacteria in saliva and tears

  • defensin proteins insert in microbial membranes

  • blood proteins sequester nutrients

  • fatty acids on skin lower pH

• Physical Removal

  • cilia/mucus movement

  • urine flushing

• Stomach Acid

Blood & Lymph Systems

Organs/Tissues

• primary- where lymphocytes develop

  • thymus & bone marrow

• secondary- where lymphocytes collect

  • spleen, lymph nodes, tonsils, adenoids, appendix

  • SALT, MALT, GALT- skin, mucus, gut-associated lymphoid tissue

  • M cells in skin, tonsils, adenoids, intestines monitor flora

Blood cells

• ~45% of blood volume

• erythrocytes- red blood cells (not part of immune system)

• platelets- involved in clotting

• leukocytes- white blood cells

erythrocytes

• red blood cells

• not part of immune system

• enucleated - nucleus has been removed (cells w/out nucleus)

• carry oxygen

platelets

• blood cells

• involved in clotting

Development of white blood cell components of the immune system (diagram)

leukocytes

white blood cells

• monocytes, dendritic cells, macrophages- phagocytic, antigen-presenting cells (APCs)

• polymorphonuclear leukocytes (PMNs or granulocytes, in blood)

• mast cells- mediate inflammation throughout body, not in blood

• lymphocytes (mostly in spleen and lymph nodes)

lymphocytes (mostly in spleen and lymph nodes)

leukocytes- white blood cells

• natural killer cells- kill infected or cancerous cells

• T cells- central to adaptive immunity

• B cells- part of adaptive immunity, produce antibodies

mast cells

leukocytes- white blood cells

mediate inflammation throughout body, not in blood

monocytes, dendritic cells, macrophages- phagocytic, antigen-presenting cells (APCs)

leukocytes- white blood cells

• engulf foreign cells, viruses, proteins

• break these down & display foreign peptides on their surface

• monocytes circulate in blood

• dendritic cells & macrophages attach to different tissues

polymorphonuclear leukocytes

leukocytes- white blood cells

(PMNs or granulocytes, in blood)

• neutrophils- phagocytic cells, migrate to site of infection

  • can use Neutrophil Extracellular Trap (NET) to kill cells

• eosinophils- anti-protozoan secretions

• basophils- inflammation mediator

neutrophils

• polymorphonuclear leukocytes

• phagocytic cells, migrate to site of infection

• can use Neutrophil Extracellular Trap (NET) to kill cells

eosinophils

• polymorphonuclear leukocytes

• anti-protozoan secretions

basophils

• polymorphonuclear leukocytes

• inflammation mediator

natural killer cells

• lymphocytes (mostly in spleen and lymph nodes)

• kill infected or cancerous cells

T cells

• lymphocytes (mostly in spleen and lymph nodes)

• central to adaptive immunity

B cells

• lymphocytes (mostly in spleen and lymph nodes)

• part of adaptive immunity, produce antibodies

Plasma proteins

soluble in fluid portion of blood (~55% of blood volume)

• fibrinogen- clotting

• antibodies

• complement

• iron sequestration & other antibacterial proteins

Inflammatory Response

Innate Immunity (second line of defense)

• a non-specific response to wounds & infection

• signs described 2000 years ago

  • redness (rubor)

  • heat (calor)

  • pain (dolor)

  • swelling (tumor)

Detection of foreign cell

Innate Immunity (second line of defense)

• triggered by unique signals of invader (MAMPs, microbe-associated molecular patterns)

• bind to Toll-like receptors (in membrane) or Nod-like receptors (in cytoplasm)

• cause transcription and release of cytokines

Clotting

Innate Immunity (second line of defense)

• clotting factors released by platelets

• attempt to contain infection

Phagocytosis

Innate Immunity (second line of defense)

• phagocyte (macrophage) engulfs microbe

  • invader is recognized because it does not have self-antigen (CD47)

  • some pathogens can avoid because of capsule

  • antibodies can increase phagocytosis (opsonization)

• microbe is killed/digested in phagolysozome

  • multiple pathways used

  • some pathogens resistant to digestion

• peptides from invader may be displayed on phagocyte surface (antigen presentation)

• peptide release can stimulate/attract other leukocytes

• macrophages also release (and are activated by) cytokines

Extravasation

Innate Immunity (second line of defense)

Extravasation brings neutrophils from nearby capillaries

• cytokines cause local endothelial cells to make selectins

• selectins/integrin/ICAM-1 retain passing neutrophils from circulating blood

• bradykinin from damaged host cells loosens connections between endothelial cells

  • allows neutrophils to squeeze out

    • attracted to wound by chemokine gradient

  • triggers mast cells in tissue to release histamines

    • causes vasodilation (blood volume increases), bringing more cells

    • vessel wall permeability increases, leading to edema (fluid buildup)

  • triggers prostaglandin release → pain

    • aspirin and related pain relievers prevent prostaglandin synthesis

Inflammation summary

• benefits of inflammation

  • increased blood volume brings in more antimicrobial agents

  • increased temperature makes phagocytes more efficient, may inhibit bacteria

  • clot may isolate area of infection

• downside of inflammation

  • may release nutrients & promote bacterial growth

  • microbe can gain access to further tissue via blood vessels

  • high fever can harm host

  • chronic inflammation damages host tissue

Complement System

• serum proteins that can work with or independent of antibodies to kill bacteria

• cascade of protein interactions leads to pores forming in bacterial membrane

Antibodies

secreted proteins that bind antigen

• four polypeptide chains, 2 light & 2 heavy, held together by disulfide bonds

  • each chain has constant (C) and variable (V) regions

    • C regions are the same for that individual/chain (allotype) and class (isotype)

      • i.e., all IgG light chain C regions in an individual are the same

    • V regions are unique to each antibody (idiotype)

  • antigen binding domains are formed by V regions of 1 H and 1 L chain

    • on a given antibody, all binding domains bind the same antigen

    • antigen=whatever antibody binds to, usually protein (carbohydrate,lipid,DNA)

      • epitope = the specific part being bound

antigen

whatever antibody binds to, usually protein (carbohydrate,lipid,DNA)

epitope

the part of the antigen the antibody is binding to

five different classes of antibody (in humans)

IgG

• IgG is bivalent, will bind 2 of the exact same antigen

• IgG is found in blood serum

IgM

• five antibody proteins held together

• longer constant domain

• generally the first Ig made in immune response

• IgM monomers in B cell membrane bind antigen, help bring it in for presentation

IgA

• two antibodies held together

• common in body secretions (tears, breast milk, mucus, etc.)

IgE

• longer constant domain (has CH4)

• binds to mast cells

• important in allergic reactions

IgD

helps antigen bind to B cells

Major Histocompatibility Complex (MHC)

• proteins that exist in plasma membrane of host cells

• unique to individual, help determine "self" (HLA type)

  • important in transplant rejection

• two types, both will bind and display antigens

  • binding of antigen depends on shape of two variable regions

  • Class I and Class II

Class I vs. Class II MHC

• Class I- all nucleated cells

  • alerts immune system that cell is infected

• Class II- B cells and antigen-presenting cells (APCs)

  • tells other immune cells that APC has found a foreign antigen

T Cell Receptor (TCR)

• is similar to MHC but only found on T-cells

• each T cell has roughly 100,000 copies of one particular type of TCR

  • each type of TCR will bind only one antigen (with limited cross-reactivity to others)

• variable region is different in each cell, ensuring a range of TCR binding specificities

B cell receptor and antibodies

• antibodies are secreted by activated B cells

• BCR has extra domain in tail to insert into membrane

Receptor interactions (chart)

Antigen Presentation

Adaptive Immunity (third line of defense)

Activation of T-helper (TH0) cells

Adaptive Immunity (third line of defense)

• a naive T-helper cell (TH0) recognizes the foreign antigen/class II MHC via its T-cell receptor (TCR) and CD4 co-receptor

  • binding of B7 & CD28 serves as confirmation signal

• APC releases cytokines, triggering development of TH0

TH0 cells chart

Cell-Mediated Immunity

Adaptive Immunity (third line of defense)

• effective against virally infected cells or cancerous host cells

• operates via activated cytotoxic T-cells (TC)

  • TC cell recognizes the foreign antigen/class I MHC on APC via its T-cell receptor (TCR) and CD8 co-receptor

  • binding of B7 & CD28 serves as confirmation signal

  • IL-2 secreted by TH1 induces proliferation of TC cells

• activated TC kills infected host cells

  • TC cell recognizes the foreign antigen/class I MHC on infected cell via its T-cell receptor (TCR) and CD8 co-receptor

    • in this case, no binding of B7 & CD28

    • signals to TC cell that it is binding to an infected cell, not an APC

  • binding results in secretion of cell killing proteins

    • perforin

    • granzymes

• proliferation is selective, i.e., only TC cells with TCR fitting foreign antigen are activated

  • activation will only occur if APC is also activating nearby TH1

  • activated TH1 will also bind to macrophages via TCR and secrete cytokines that activate macrophages and promote inflammation

perforin

• cell killing proteins - cell mediated immunity

• protein which inserts in infected cell membranes, makes pore

granzymes

• cell killing proteins - cell mediated immunity

• proteins which trigger apoptosis, programmed cell death

Humoral Immunity

Adaptive Immunity (third line of defense)

• effective against any pathogen outside a host cell (viruses, bacteria, protists, etc.)

• operates via differentiated B-cells

• can happen two ways

  • direct encounter of antigen

    • antigen binding to B-cell receptor (BCR) causes clustering (capping)

    • B-cell differentiates into plasma cells (secrete IgM) and memory cells

  • interaction with TFH/ TH2

Steps in antibody formation (diagram)

interaction with TFH/ TH2

Humoral Immunity

• B cells can act as APCs for antigens bound to its BCR

  • internalize that antigen and display it in class II MHC

• TFH/ TH2 cell recognizes the foreign antigen/class II MHC on B cell via its T-cell receptor (TCR) and CD4 co-receptor

  • binding of CD154 & CD40 serves as confirmation signal

• TFH/ TH2 cell releases cytokines that initiate B cell differentiation

  • class-switching of heavy chains occurs (all classes possible)

  • new cells all recognize same antigen (clonal selection)

  • plasma cells- secrete antibodies

  • memory cells- long lived

• higher number of B cells specific for that antigen after first exposure

  • don't require TH activation to convert to plasma cells, just binding to BCR

  • hypermutation of variable region may give even higher affinity antibodies

plasma cells

secrete antibodies

memory cells

long lived B cells

• don't secrete antibodies

• exist to ensure faster, stronger response to second exposure

What can the immune system can do?

• respond to anything, even if never encountered before (antibody/receptor diversity)

• strengthen its response upon encountering something (clonal proliferation and memory)

• discriminate between self and non-self (clonal deletion)

What Happens When a Virus Infects a Person?

• Virus enters those body cells with the proper receptor, begins replicating

  • new viruses are produced → free (extracellular) virus particles

  • however, some viral antigens will be displayed on surface of infected cell by MHC I

• Macrophages and other APCs will engulf free virus particles

  • APCs typically encounter virus in spleen, lymph node, other specialized tissue

  • display viral antigens in MHC II and MHC I

• A few TH0 cells will have a TCR that fits the combination of MHC II/antigen on APC

  • TH0 cells bind to APC via TCR and CD4

  • causes APC to release cytokines, causing that specific TH cell to proliferate

    • can differentiate into TH1 and/or TH2 depending on cytokines present

    • in either case, more copies of TH with TCR recognizing that particular viral antigen

  • activated TH cells will release cytokines as well

• Separately, a few TC cells will have a TCR that fits MHC I/antigen on APC

  • TC cells bind APC via TCR and CD8

  • activated TH1 cells induce proliferation of that specific TC cell

    • therefore, more copies of TC with TCR recognizing that viral antigen

• TC cells migrate to site of infection

  • TC cells bind to virally infected cell via TCR and CD8

  • causes TC cell to release proteins that kill the infected cell

• Separately, a few B cells will have a BCR that fits free virus

  • B cells will endocytose virus bound to BCR and display antigens in MHC II

  • TH2 cells bind to B cell via TCR and CD4

  • activated TH2 cell induces differentiation of that specific B cell

    • plasma cells make lots of antibody specific for that viral antigen

    • memory cells for that viral antigen are defense against future infection

• Eventually, infection is brought under control by

  • TC cells killing virally infected cell

  • antibody neutralization of free virus

• Reinfection leads to rapid secondary response

Function of Antibodies

• Virus or toxin neutralization

  • bind to viral surface or toxin and prevent intended interaction of virus or toxin with host

• Agglutination/Precipitation

  • clump antigens together

  • if soluble antigen, may cause it to precipitate

• Activate complement system of proteins

  • antibody bound to bacterial cell surface triggers binding/cleavage of complement proteins

  • cleaved complement proteins cause inflammation

  • other fragments of complement proteins insert into membrane

    • pores form, cell dies

    • doesn't work for Gram positives

• Opsonization

• antibodies and complement on cell surface "flag" cell for phagocytosis

  • works for all bacteria

• can also clump cells or toxin molecules leading to easier phagocytosis

Generation of Antibody Diversity

• Each B cell produces only one kind of antibody

• Ability to respond to anything out there depends on millions of different B cells, millions of different antibodies

• diversity is created by uniquely splicing DNA segments in each B cell

• Similar processes result in TCR diversity

Antibodies are proteins, does this mean there are millions of different antibody genes?

• NO, diversity is created by uniquely splicing DNA segments in each B cell

• multiply the segments to realize the possibilities

  • remember that C region determines class, is not involved in antigen binding

  • 320 light chains x 16,200 heavy chains = > 5 million binding specificities

• even more variation because of

  • imprecise joining of segments

  • high mutation rate during B cell proliferation

Natural active immunity

disease exposure

• infection leads to immune response, boost in memory cells (takes weeks)

• second exposure results in stronger, faster response

Artificial active immunity

vaccination

• vaccination leads to immune response (takes weeks)

  • whole organism- killed or attenuated

  • subunit- natural, modified or recombinant

  • hapten + carrier molecule- when antigen is too small on its own

• second exposure (or booster) results in stronger, faster response

Natural passive immunity

maternal immunity

• antibodies are received from mother through placenta, breast milk (instant protection)

• no host immune response, no boost for later exposure

Artificial passive immunity

antitoxins

• injection of antibodies from another individual or animal (instant protection)

• used against toxins

• no host immune response, no boost for later exposure

Immune Disorders

• Allergies can be an overreaction of the immune system

• Autoimmune diseases- the immune system attacks self-antigens

• Superantigens can activate T cells indiscriminately and destabilize the system

The devastating effect of HIV

Clonal Selection in recognition of self and non-self

• Each B & T cell makes a unique antibody or TCR

  • When binding to antigen, proliferation occurs

  • a clonal line is expanded

  • descendent cells produce identical antibody or TCR (except for mutation)

• During embryonic/neonatal development, those B & T cells that bind antigen (presumed to be self) are deleted

  • B cells mature in bone marrow; T cells mature in thymus

  • it is thought even in adults, those tissues are kept free of "new" antigens

  • if maturing cell does not react with MHC, it dies

  • if maturing cell does react with antigen, it dies

clonal line expansion diagram

What is critical to effective treatment?

Identification by Microscopic Observation

• Staining/morphology is rarely definitive (for bacteria)

  • however, the appearance of some organisms in conjunction with symptoms and location sampled can often be presumptive (enough to start treatment)

• Specialized staining techniques can highlight microbes in tissue figure

Identification by Growth and Biochemical Tests

• Proper plating/media

  • media should be enriching, if not selective

  • failing that, a differential medium can distinguish between species

  • must maintain temperature and oxygen conditions

• Identification by metabolic fingerprint, the results of multiple biochemical tests

  • based on flow charts for identification

  • now worked into strips/kits

  • or even automated

Immunological Methods Overview

• Current infection can be detected by using lab antibodies to detect antigen in patient

• Past infection can be inferred by detecting patient antibodies in blood using lab antigen

  • antibody titer can be a signal of time of infection

  • draw blood, spin out cells

  • dilute serum by factors of 2

  • look for reaction against lab antigen

Precipitation/Agglutination

Immunological Methods of Detection

• at equal concentrations of antibody and antigen, bridging will occur

• will precipitate soluble antigen and agglutinate (clump) cells

  • is the basis for blood typing

  • allows rapid detection of some infectious agents (or specific strain for epidemiology)

Fluorescent Microscopy Direct Method

Immunological Methods of Detection

Useful in identifying cells

This method tests for antigen in patient

• antibodies are conjugated to fluorophore

• conjugated antibodies are allowed to bind to cell suspension from patient

• will bind if antigen is on cell surface

• can be examined by light microscopy

Fluorescent Microscopy Indirect Method

Immunological Methods of Detection

Useful in detecting past exposure

This method tests for antibodies in patient serum (past exposure)

• serum from patient is collected

• serum is mixed with test antigen

  • if antibodies present, will bind cells

  • if not, serum is washed away

• secondary antibody with fluorophore added to cells

  • 2º ab must be from other species

  • 2º ab binds to any ab from 1st species in Fc region

  • e.g., 2º ab = rabbit anti-human IgG

• can be examined by light microscopy

• Use of 2º ab saves time & trouble adding fluorophore to serum antibodies; labeled 2º ab binds to many different serum ab

Fluorescent Microscopy

Immunological Methods of Detection

• direct method (useful in identifying cells)

• indirect method (useful in detecting past exposure)

• can be used in combination with a cell sorter (FACS machine)

  • laser activates fluorescently labeled cells (labeled antibody bound to surface antigen)

  • charge difference is used to separate cells

Immunoelectron Microscopy

Immunological Methods of Detection

• antibodies are conjugated to gold bead

• conjugated antibodies allowed to bind to cell section

• will bind wherever antigen is

Enzyme-Linked Immunosorbent Assay (ELISA)

Immunological Methods of Detection

• direct ELISA- tests for antigen (antigen capture)

• indirect ELISA-tests for antibody

• detection based on colorimetric enzyme reaction

  • because of enzyme, more sensitive than fluorescent methods

• must conjugate enzyme to constant region of antibody

  • amazingly, does not affect antibody binding or enzyme activity

direct ELISA

Immunological Methods of Detection

Tests for Antigen (Antigen Capture)

• unconjugated antibody stuck to well

• antigen allowed to bind

• enzyme conjugated antibody then added

• color based reaction carried out

• strength of color depends on how much antigen bound

indirect ELISA

Immunological Methods of Detection

Tests for antibody

• antigen stuck to microtiter well

• serum from patient passed over

  • if antibodies present, will bind antigen

  • if not, serum is washed away

• enzyme-conjugated 2º antibody added

  • example- 2º ab = rabbit anti-human IgG

• color based reaction carried out

• strength of color depends on how antibody titer in patient serum

Immunoblot (Western blot)

Immunological Methods of Detection

• run proteins out on gel

• blot proteins onto membrane

• add unlabeled (primary) antibodies for specific protein

• add enzyme-conjugated (secondary) antibodies against first antibodies

• reaction will occur where antibody is bound

Antibody-based rapid detection methods

Immunological Methods of Detection

• advantage- fast, no culturing required, immediate treatment based on result

• disadvantages- false positives and negatives, no information about antibiotic resistance

• blood, sputum or urine (with antigen) added to one end of filter strip

  • capsular protein from Streptococcus pneumoniae in example above

  • beta subunit of human chorionic gonadotropin in pregnancy test

  • spike or nucleocapsid protein for rapid Covid tests

• capillary action carries fluid through region with labeled-antibody for particular antigen

  • labeled antibodies are mobile

  • will be carried along by fluid (with or without antigen binding)

  • are from species 1 (rabbit in the example above)

• fluid passes line of immobilized antibodies for antigen

  • labeled antibodies will stop on test line if bound to antigen

• fluid passes on to second line, immobilized antibodies for species 1

  • must be from second species (goat in above example)

  • serves as control, to ensure labeled antibodies were carried past test line

PCR

Nucleic Acid Methods (NAAT = Nucleic Acid Amplification Tests)

• use primers for distinctive genes

  • size of fragment can indicate species and strain, antibiotic resistance

  • can be multiplex, i.e., include primer pairs for multiple genes

• sensitive and fast (no culturing)

RT-PCR

Nucleic Acid Methods (NAAT = Nucleic Acid Amplification Tests)

Used to detect RNA from pathogen, especially for RNA viruses (Covid tests)

qRT-PCR

Nucleic Acid Methods (NAAT = Nucleic Acid Amplification Tests)

• follow increase in product, tells you how much starting template there was

• can track viral loads during infection

Tests for SARS-CoV-2 (chart)

Diagnostic tests for SARS-CoV-2

Detect current infection

Antibody tests for SARS-CoV-2

Detects past infection (at least 2 weeks ago)

• starts with a blood sample

• detects IgM and/or IgG specific for the virus

• may help determine when person was infected or if they can donate plasma

• may provide data for epidemiological models

• if not specific enough (cross-reacts with cold viruses), false positives a problem

Antibiotics

Antimicrobial compounds produced by microbes

• source is typically fungi or soil bacteria

• Exhibit selective toxicity

  • antibiotic must target something unique about pathogen

• May also have side effects

  • typically = allergies, stomach upset, diarrhea, kidney and/or liver damage

  • side effects are dosage dependent

• Effective range varies

  • drugs can be broad or narrow spectrum in terms of effectiveness against pathogens

  • may kill pathogen (bactericidal) or limit its growth (bacteriostatic)

• Commercial antibiotics can be natural, synthetic or semi-synthetic

Commercial antibiotics can be natural, synthetic or semi-synthetic

• growing the organism & purifying the drug (at scale) can be technical challenges

  • took ~ 15 years from discovery to introduction of penicillin

    • first successful treatment of systemic infection (1942) used half available supply

    • within two years, was being mass-produced

  • best source strain = isolate from moldy cantaloupe in Peoria IL

  • growth medium = corn steep liquor

  • deep tank fermentation resulted in best yields

    • how to introduce oxygen without contaminating the culture

• natural drugs are often modified

  • natural penicillin is rapidly excreted

  • probenecid given with penicillin to outcompete penicillin excretion

  • synthetic penicillin makes this unnecessary

Modes of antibiotic administration

• oral- must be acid tolerant, well absorbed

• topical- typically only for superficial infections

• injection- most direct, but also most difficult

Antibiotic Resistance

• a predictable evolutionary result

  • selection for resistance increases their numbers

  • horizontal gene transfer spreads resistance genes

  • we should limit indiscriminate antibiotic use

• an increasing problem, especially in hospitals

  • need to find new drugs or modify old ones

• determinizing effectiveness

  • Kirby-Bauer method

  • Minimum Inhibitory Concentration (MIC)

Mechanisms of Antibiotic Resistance

• reduced permeability of cell envelope

  • alter pore proteins (for hydrophilic antibiotics)

  • alter membrane lipids (for hydrophobic antibiotics)

• efflux pumps to transport drug out

  • may add on to existing transport systems

• inactivate antibiotic

  • by cleaving it

  • by modifying it

• mutate target of action

• avoid/alter target pathway

Kirby-Bauer method

Antibiotic resistance determinizing effectiveness

• uses disk diffusion method

• compare diameter of zone of inhibition to standard

• must maintain consistency of medium, temperature, etc.

Minimum Inhibitory Concentration (MIC)

Antibiotic resistance determinizing effectiveness

• determine by dilution or test strip

• in vivo levels don't match in vitro tests

Steps in peptidoglycan synthesis

Cell Wall Synthesis

• synthesis of NAG & NAM-peptide precursors

• transport across cytoplasmic membrane by bactoprenol

• polymerization into existing wall by transglycosylases

• cross-linking chains by transpeptidases

Beta-lactam antibiotics

Antibiotic - Cell Wall Synthesis

• examples- penicillin, cephalosporin

• mechanism- resembles D-ala dipeptide, competes for binding to transpeptidase

• used against- Gram-positives, some Gram negatives (OM limits access to wall)

• resistance- enzymes which break down antibiotic

Vancomycin

Antibiotic - Cell Wall Synthesis

• mechanism- binds to peptides, interferes polymerization and cross-linking

• used against- Gram positives, drug of last resort

Cycloserine

Antibiotic - Cell Wall Synthesis

• mechanism- interferes with formation of D-ala dipeptide

• used against- Mycobacterium

Bacitracin

Antibiotic - Cell Wall Synthesis

• mechanism- interferes with bactoprenol, peptidoglycan subunit transfer

• used against- Gram positives

Gramicidin

Antibiotics - Membrane Integrity

• a cyclic peptide with D and L amino acids

• mechanism- inserts into membrane, creates pores

Polymixin

Antibiotics - Membrane Integrity

• polypeptide

• mechanism- acts like detergent to disrupt cytoplasmic membrane

• used- topically (also disrupts human cell membranes)

Daptomycin

Antibiotics - Membrane Integrity

• non-ribosomal peptide (i.e., an enzyme, not ribosome, links amino acids together)

• mechanism- forms ion channel

Quinolones

Antibiotics - DNA Synthesis and Structure

• examples- nalidixic acid, ciprofloxacin

• mechanism- interfere with DNA gyrase

• used against - broad spectrum