5 organisms that can cross the placenta
rubella, cytomegalo virus, HIV, Treponema pallidum, listeria
EESMDO
encounter, entry, spread, multiply, damage, outcome
Exogenously acquired diseases
From outside the body. Exogenously acquired diseases are those that result from an encounter with a microbe in the environment. (EX: common cold, gonorrhoea, surgical infection, malaria, typhoid fever, coccidoidomycosis)
Endogenously acquired diseases
acquired diseases from agents present in or on the body (normal flora)
EX: cut can lead to the production of pus caused by the staphylococci that inhibit healthy skin
Colonisation
the presence of microorganisms in a site of the body that may or may not lead to tissue damage and signs and symptoms of disease
Infection
condition whereby colonisation within a human host progresses to cause disease
What is the most common infection?
Respiratory infection
Ingress
Entry w/o penetration through tissues (w/o crossing epithelial barriers)
EX: cholera, whooping cough, bladder infections
Penetration
Entry into tissues after crossing epithelial barriers
EX: insect bites, cuts and wounds, organ transplants, blood transfusions, and inoculum size
Inoculum size
the # of invading organisms
Bacteria from body sites
skin: e. coli, staphylococcus epidermidis, s. aureus
vagina: streptococci, staphylococci, bacteroides, fusobacterium
Resident biota
a large array of microorganisms that favourably inhabit the human body in abundance
Transient microbiota
colonises the superficial layers of the skin; amendable to removal by routine hand hygiene.
transient v. resident microbiota
transient microbiota are present for a relatively short time
Opportunists
cause disease when given opportunity
5 roles of normal flora
- Microbial antagonism: the most significant (competitive exclusion)
- Stimulate the immune system and provide antigens to train IS
- Provide vitamins B12 and K
- Can be a common source of infection
- Help digestion
Symbiosis
The relationship btwn normal microbiota and the host
commensalism, mutualism, parasitism
Commensalism
one organism benefits and the other is unaffected
Mutualism
both organisms benefit
Parasitism
One organism benefits at the expense of the other
What kind of symbiotic relationship exists btwn humans and members of their normal microbiota?
commensalism
Why is skin a hostile place for bacteria?
- Crowded conditions (keep out invaders)
- Dry skin
- High salt
- Sloughing off of dead cells
Microbiota can grow back to near-normal numbers within
approx. one day
Losing a large area of the skin (burn victims) most probable cause of death
Psuedomembranous colitis
Pseudomembranous colotis
antibiotic associated diarrhoea caused by Clostridium difficile
Harmful effects of normal biota
- use vitamins
- chemical conversions
Helpful effects of normal biota
- Microbial antagonism
- Stimulate the immune system
- Provide supplemental vitamins (B12 and K)
The three challenges
nutrition, occupancy, and resistance
Nutrition as a challenge
intermittent availability of food
Occupancy as a challenge
need to remain in a certain habitat - avoid being washed away by liquid
Occupancy as a challenge
Colonisation
Resistance as a challenge
resistance to damaging agents such as antibiotics
Feast and famine
Bacteria feast for a given time then go through famine stage. This increases bacterial population growth rate but decreases total population size.
Colonisation
Bacteria must be able to remain in a given place and avoid being washed away by liquid contents
T/F: All bacteria are smaller than eukaryotic cells?
FALSE, there are always exceptions
Small size promotes metabolic efficiency
Surface area grows slower than volume
- High SA: V increases as size of cell decreases
Issues in bacterial colonisation
- Sweep away by liquid currents: adhere to epithelial cells
- Kill microbes w/ host phagocytes
- Starve microbes for lack of needed nutrients
- Inhibit growth by secreting antimicrobial factors such as cationic peptides
Avoid being taken up
Slimy capsules
Kill the phagocyte
Toxin punches hole in neutrophil membrane
Derive needed nutrients from host cells
Lyse RBCs and use the iron
Structure of Gram (+) peptidoglycan layer
Thick multilayer peptidoglycan murein (cell wall)
Murein
sugars (glycan) chains that are cross-linked to one another via peptides; critical component in maintaining rigidity of both G+ and G-; larger role in G+
Structure of Gram (-) peptidoglycan layer
Use an outer membrane outside the murein cell wall made of Lipid A, the core, and O-antigen.
Outer membrane (G-)
- Made of Lipid A, the core, and O-antigen.
- Functions as an endotoxin.
- Protects against antibiotics and disinfects
Disadvantage of outer membrane (G-)
some bacteriophages use outer membrane proteins as attachment sites for infecting their host bacteria
Which one has Teichoic acid and Lipoteichoic acid in their cell wall?
G+
What biological roles are played by peptides that contain D- amino acids?
- Structural function in cell wall
- Growth fitness
- Biofilm development
- Spore germination
- Signaling
How does gram staining work?
What kind of cell wall
G+ - crystal violet - no cell wall
G- - pink - cell wall
Cytoplasmic membrane
Contains the enzymes and equipment that carry out photosynthesis and respiration as well as transporting molecules in and out of the cell.
How do bacteria protect the cytoplasmic membrane?
G+ - peptidoglycan cell wall
G- : outer membrane
Mycobacterium - large amounts of waxes in cell walls
Mycoplasma
- Naturally lack cell wall
- Extremely tiny (pleomorphic cells)
- Cell membrane stabilised by STEROLS and resistant to lysis
- Offset turgor pressure by pumping Na+ out of cells
- Most important medical species: Mycoplasma pneumoniae
Most important medical species of Mycoplasma
Mycoplasma pneumoniae
Pleomorphic cells
Mycoplasmas
Prokaryotes
- No nucleus (DNA in nucleoid)
- No membrane-bound organelles
- Cell wall contains peptidoglycan
- Less than several micrometers in size
Eukaryotes
- Nucleus
- Membrane-bound organelles
- No peptidoglycan is cell wall is even present
- May be 10x larger than prokaryotes in size
Flagella arrangement: Monotrichous
single flagellum at one pole
Flagella arrangement: Amphitrichous
single flagellum at each pole
Flagella arrangement: Lophotrichous
two of more flagella at one pole
Flagella arrangement: Peritrichous
flagella all over surface of cell
Structures ONLY in prokaryotes: Capsule
well organised layer composed of polysaccharides that surround cell wall
Structures ONLY in prokaryotes: Slime layer
like a capsule, but more loosely associated with cell wall.
Purpose of slime layer
1) make cell virulent
2) attachment
3) avoid dehydration
Structures ONLY in prokaryotes: Endospores
Bacillus, Clostridium, Sporosarcina: Sporolactobacillus, Thermoactinomycetes contain calcium - dipicolinic acid, heat resistant
Protoplast
Lack all traces of a cell wall (G+ rxn to lysozyme)
Lysozyme
destroys bacterial cell walls
Spheroplast
Lack most of cell wall (G- rxn to lysozyme)
L forms
strains of bacteria that sometimes lose their ability to make cell walls
Plasmids
genetic structure that can replicate independently from chromosomes. typically small and circular shaped; in cytoplasm of bacterium or protozoan
5 modes of action of antibiotics
- Inhibition of cell wall synthesis
- Inhibition of protein synthesis
- Inhibition of nucleic acid synthesis
- Inhibition of folic acid synthesis
- Disruption of cell membrane
Inhibition of cell wall synthesis
Penicillins, Cephalosporins, Vancomycin, Bacitracin
Inhibition of protein synthesis
Chloramphenicol, Tetracyclines, Streptomycin, Erythromycin
Inhibition of nucleic acid synthesis
Ciprofloxacin, Rifampin, some anti-viral agents
Inhibition of folic acid synthesis
Sulfonamides
Disruption of cell membrane
Polymyxin B, antifungal agents
Vancomycin
Glycopeptide antibiotic antibiotic used for G+ infections (staphs, streps, and enterococci)
Penicillin
Affect peptidoglycan synthesis where biosynthetic target is absent in the host
Penicillin can...
cause strong allergic rxn
Bacitracin antimicrobial drugs...
affect many targets in prokaryotic cells
Fungal and protozoan infections are more difficult to treat because...
the cells are similar to human cells
Paul Ehrlich
developed the concept of chemotherapy to treat microbial disease
Magic Bullet
Paul Ehrlich; kill pathogens but not human cells
Alexander Fleming (1928)
discovered penicillin produced by Penicillium notatum
First clinical trials of Penicillin were done in...
1940
The first antimicrobial agents used to cure infections in humans
Sulfonamides
Why do Sulfonamides kill bacteria without bothering the host?
Bacteria must synthesise their own folic acid. When sulfonamides are added, it competes with and ultimately displaces pBMA and stops folkc acid synthesis. Because humans cannot make folic acid, we are not bothered.
Sulfa drugs...
interfere with bacteria cell metabolism
General action...
is either by:
- Directly killing microorganisms (Bactericidal)
- Inhibiting their growth (Bacteriostatic)
A narrow-spectrum drug...
affects only a single microbial group
A broad-spectrum drug....
is effective against two or more groups of microbes
Attributes of an ideal antimicrobial agent
Solubility in Body Fluids
agents must dissolve in body fluids
Attributes of an ideal antimicrobial agent
Selective Toxicity
agents must be more toxic to microorganism than to host cells
Attributes of an ideal antimicrobial agent
Toxicity is not easily altered
The agents should maintain a standard toxicity and not be made more or leas toxic by foods or other drugs
Attributes of an ideal antimicrobial agent
Nonallergenic
No allergic rxns
Attributes of an ideal antimicrobial agent
Maintenance of constant therapeutic concentration in blood and tissue fluids
should be sufficiently stable and degraded and excreted slowly
Attributes of an ideal antimicrobial agent
Resistance
Resistance by microorganisms not easily acquired
Attributes of an ideal antimicrobial agent
Shelf life
Shelf life should be long
Attributes of an ideal antimicrobial agent
Cost
Cost should be reasonable
Selective toxicity
Agents are more toxic to microorganisms than to host cells
What must Beta-Lactam antibiotics do?
- Associate with the bacteria
- In G-, must penetrate OM and periplasmic space
- Interact with penicillin-binding proteins of the cytoplasmic membrane
- Activate an autolysin that degrades the cell wall
What are the 2 classes of Beta-Lactamases?
1) Penicillinases
2) Cephalosporinases
Resistance is now...
widespread because of plasmids and jumping genes (TRANSPOSONS)
MRSA
- Methicillin
- Resistant S. aureus
- Can be treated with VANCOMYCIN
Tolerance
Partial resistance, bacteriostatic but not bactericidal b/c the lack of sufficient levels of the suicidal autolysin
Synergism
Penicillin + Streptomycin
- Penetration of streptomycin often enhanced
Antagonism
Chloramp + Penicillin
- Blocks per syn and prevents cell growth required for penicillin to function
Indifference
Each drug works no better or no worse alone or in combination
What are supergerms?
Bacteria resistant to 15 or More antibiotics (e.g. Enterococci)
Most common resistance to antibacterial agents
Penicillins, cephalosporins, carbapenems
Modification of the drug
- Hydrolysis of beta-lactam ring by beta-lactamase
Most common resistance to antibacterial agents
Methicillin (MRSA)
Target modification: acquisition of a resistant penicillin-binding protein (NOT in b-lactamase)
Most common resistance to antibacterial agents
Tetracyclines
Efflux pump transports the drug out of the cell
Most common resistance to antibacterial agents
Aminoglycosides (gentamicin, tobramycin, amikacin, streptomycin, etc.)
Modification of the drug by R-Plasmid encoded enzyme; reduced affinity for the ribosome and reduced transport into the cell
Most common resistance to antibacterial agents
Sulfonamides
Target modification: sulfanilamide-resistant dihydropteroate synthase
Most common resistance to antibacterial agents
Trimethoprim
Target modification: trimethoprim-resistant dihydrofolate reductase
Most common resistance to antibacterial agents
Erythromycin
Target modification: methylation of 23S ribosomal RNA
Most common resistance to antibacterial agents
Chloramphenicol
Modification of the drug: acetylation of hydroxyl groups by chloramphenicol transacetylase; interference w/ transport into cell
Most common resistance to antibacterial agents
Oxazolidinones (linezolid)
Target modification: mutations in 23S ribosomal RNA
Most common resistance to antibacterial agents
Quinolones (nalidixic acid, ciprofloxacin, etc.)
Target modification: mutations in genes encoding DNA gyrase and topoisomerase IV
Most common resistance to antibacterial agents
Vancomycin
- Target modification: change in binding site in the peptidoglycan target
- Restricted access to drug target
Most common resistance to antibacterial agents
Daptomycin
Restricted access to drug target
Why does resistance spread so fast?
Plasmids and jumping genes (TRANSPOSONS)
Beta-lactamases
Enzymes produced by bacteria that provide multi-resistance to B-lactam antibiotics (penicillins, cephalosporins, cephamycins, and carbapenems)
List 4 schemes that bacteria have evolved to gain resistance to antibiotics
1) Inactivation of antibiotics
2) Efflux pumping of the antibiotics
3) Modification of the antibiotic target
4) Alteration of the pathway
All of the following are mechanisms of resistance except:
activation of antibiotic
The best way to deal with antibiotic resistance is to use
all of the prescribed antibiotic
Resistance to antibiotics seen at the level of a ribosome is caused by
changes in the shape of the ribosome (changes in proteins around ribosomes make it impossible for antibiotic to find it)
What will allow you to classify the organism as belonging to bacteria but not archaea or eukarya?
cell walls are made primarily of peptidoglycan
Which of the following is NOT a typical characteristic of most bacterial plasma membranes?
Contains cholesterol
Do plasmids exist in other (not bacterial) cells?
YES; fungi and chloroplasts of plants
Bacteria use 3 strategies to protect their cytoplasmic membranes
1) G+ use thick multilayer peptidoglycan murein (cell wall)
2) G- use an OM, outside murein cell wall, made of Lipid A, the core, and O-antigen
3) Acid-fast bacteria, such as Mycrobacterium tuberculosis, contain large amount of waxes in their cell walls
Big 4 typical bacteria
- G+ cocci
- G+ rods
- G- cocci
- G- rods
Spirochetes
- Treponema
- Leptospira
- Borrelia
G+ Rods
- Bacillus anthracis
- Clostridium tertani
- C. botulinum
- C. perfringens
- C. difficile
G- Rods
- Enterobacteriaceae
- Escherichia
- Enterobacter
- Salmonella
- Shigella
- Klebsiella
- Proteus
- Citrobacter
- Serratia
- Yersenia
IMPORTANT G- RODS
- Vibrio cholerae
- Campylobacter jenuni
- Helicobacter pylori
Fastidious small G- Rods
- Haemophilus
- Bordetella
- Brucella
- Francisella tularemia
- Bartonella
- Legionella pneumophila
NOT SO TYPICAL bacteria
- Mycobacterium: M. tuberculosis, M. leprae
Rickettsiae
strict parasites