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New tools enabled the development of microbiology
The development of microbiology was closely linked to tools that allowed people to see microbe
Microscopes enabled people to see individual microbe cells
Agar plates allowed people to see communities of microbes (colonies)
The first microscope
1665: fungal fruiting bodies were first observed, with drawings published by english naturalist robert hooke.
this used a multi-lens compound microscope he developed
1676: bacterial cells were first observed by the Dutch scientist Antonie van leeuwenhoek.
He designed and used a single lens microscope
spontaneous genration theory
300BC: aristotle belived that a ‘vital force’ forma life
The spontaneous generation theory help that living organism could arise from non-living matter
disproving spontaneous generation theory
1864: Louis Pasteur filled flasks with rich broth. He sterilised the broth by heating and created a ‘swan’s neck’ in the flasks.
When the flask remained upright but open to the air, the broth remained sterile.
Tilting the flask brought the liquid broth into contact with the bend, resulted in growth in the broth.
➢This provided strong evidence to disprove the spontaneous generation theory.
➢ It strengthened the biogenesis theory (all life comes from preexisting life)
biogenesis theory
the biogenesis theory held that living organisms could only arise from pre-existing life
the first vaccine
1798: Edward Jenner showed that inoculating a healthy person with cowpox infection material protected from smallpox.
germ theory of disease
1835: Agostino Bassi showed that a silkworm disease was caused by a fungus. This was the first microorganism recognised as causing an infectious disease.
handwashing
1847: Ignaz Semmelweis advocated handwashing to prevent transmission of child-bed fever between patients.
Two wards, one with doctors and midwifes, rates of diseases much higher to in doctors ward, due to doctors training medical students on autopsies, who would then go upstairs to deliver babies
pasteurisation
1862: Louis Pasteur demonstrated that heating wine for a short period killed the microbes responsible for wine spoilage. This process was named pasteurisation.
disinfectant
1867: Joseph Lister treated surgical wounds with phenol (carbolic acid), reducing post-operative infections. This was the first disinfectant.
growing bacteria
1876: Robert Koch was the first to grow bacteria in pure culture – with help from Angelina Hesse.
With this breakthrough, Dr Koch devised a set of 4 experimental steps known as Koch’s Postulates to show a link between a bacterium and a disease.
He used these to identify bacteria causing anthrax, tuberculosis, and cholera. These steps are still used today.
What are bacteria
Single celled microbes, in contrast to acellular microbes (such as viruses)
Bacteria are prokaryotes,
Bacetria are everywhere, abundant in seawatera nd soil associated with plants and animals
Bacteria make up out microbiota (beneficial icrobes)
Occasionally, they can cause disease
found in nearly every niche on the planet, may be adapted to extremes
Bacteria have both positive and negative effects on us
Negative
Human disease
Plant and animal disease
Food and material spoilage
Positive effects
Biochemical cycles
Producing O2
Breaking down dead organic matter
Nitrogen fixation and nutrient cycling
Agriculture and food production
Biotechnology
Bioremediation
Basic research
Bacteria are prokaryotes
Pre-nucleus, includes bacteria and archaea
Eukaryotic cells are larger and more complex than prokaryotic cells
Doesn't have organelles, relies of surface area to volume ratio, so cannot get too big
Lack nucleus, instead have nucleoid
Divide by binary fission
Lack intracellar organelles
Rigid cell wall
Surface organelles (motility, attachment)
key processes of bacteria
Metabolism:
Uptake of chemicals from environment, their transformation within a cell, and elimination of wastes into the environment cell is thus and open cell system
Reproduction (growth)
Chemicals from environment are turned into new cells under direction of preexisting cells
Differentiation
Formation of new cells structure such as a spore, usually as part of a cellular life cycle
Communication
Cells communicate or interact primarily by means of chemical that are released or uptaken
Movement
Living organism are often capable of self-propulsion
biofilm
Biofilms are structures of bacterial communities attached to surfaces.
Held together by polysaccharides, secreted by the bacteria.
Protect bacteria from toxins and predators.
Medically important because:
they form on many solid surfaces, including teeth or medical devices.
Bacteria become resistant to antibiotics and immune cells
How are bacteria classfiied
Classification of microorganisms places them into groups with evolutionarily-related organisms.
Early classification of bacteria was based on physical traits (phenotypicproperties) that could be observed or measured, including:
Morphology (cells, colonies)
Differential Staining
Motility
Metabolism
Habitat
Pathogenicity
However phenotypes are not always reliable for classification
Distant relatives might appear similar, while close relatives might not appear similar.
Phenotypes can change – depending on environment or other signals.
Relatedness is difficult to quantify based on phenotypes.
phylotyping
Physical traits may change, but DNA sequence does not.
Phylotyping is the comparison of the DNA sequences of specific genes. It is a reliable way to establish evolutionary relationships (= phylogeny).
Genes that are useful for phylotyping must:
be widely distributed
be highly conserved
contain regions of variation
not be spread by horizontal gene transfer
Widely used phylotyping genes include components of ribosomal RNA.
16S rRNA prokaryotes
18S rRNA eukaryotes
Process of phylotyping eg with bacteria 16S small subunit rRNA
16S rRNA gene is sequenced
Aligned with sequence from other organisms
Alignments used to generate a phylogenetic tree
Universal phylogenetic tree of life
16S and 18S sequences reveal the evolutionary history of all cells
There are three domains of life: bacteria, archaea, and eukarya.
Bacteria and archaea are very distinct evolutionarily.
All cells descend from a single ancestor, LUCA (=last universal common ancestor)
Common shapes of bacteria
Bacteria have a range of cell shapes, size, and ararangements
Variations in cell morphology enable adaptation to a range of environments.
Common shape insclude
Rod
Coccus
spirilum
less common shape include:
spirochete
budding and appendages bacteria
filamentous
Some like spirochete are more adapted to living in a host, while filamentous and stalk and hydra are more adapted to living in environment
Bacteria can undergo cell division where it stays togetehr instead of completly seperating. Shape depends on how they divide: (along what plane)
Shape can tell what adapted for
Arrangements of rod-shaped bacteria
(bacilli (rods)
Eg myccobacterium tubercolosis:
Streptobacilli:
Strepto=twisted; bacilli=rods
Eg ballcillus anthracis
Arrangement of coccoid arrangemetns
Cocci=spherical:
diplococcus: two
streptococcus: string
staphylococcus: 2d triangle
tetrad: square
sarcina: cube
Arrangement of spiral shape bacteria
vibrio: one curve
spirllium: spirally curve
spirochete: thin
Structure of bacteria
Bacteria consist of the following
A cytoplasmic membrane,
usually surrounded by cell wall and sometimes an addition outer layer
An internal cytoplasm
contains ribosomes, chromosomes, and enzymes
External structures
Such as capsules flagella, and pili
inside bacteria
Bacteria cells contain ribosomes, a nucleoid, and other components in their cytoplasm
Unlike eukaryotic cells bacteria do not have intracellular organelles
Dna all in one place, so can adapt faster than eukaryotes
The bacterial nucleoid contains DNA (the chromosome) organised by DNA-binding proteins but not enclosed in a nuclear membrane
The cytoplasmic membrane
The cytoplasmic membrane forms the boundary between a cell and its environment.
It is semi-fluid, comprised of a phospholipid bilayer and embedded proteins, which may form channels.
Its main function is to regulate movement of materials in and out of the cell by transport mechanisms.
The bacterial cell wall
Doesn't really keep anything inside the cell (the cell membrane dosent that)
Bacterial cell wall is made outside the cytoplasmic membrane
It is made of multiple layers of peptidoglycan, which is extensively covalently linked and strong (like a chain link fence)
Gram-positive cell envelope
Thick layer of peptidoglycal on surface that interacts with environment
Gives very rigid structre, determines shape of cell
Eg of pathogens incl. Staphylococcus aureus, Streptococcus pyogenes, Listeria monocytogenes, Bacillus anthracis, Clostridium tetani
The gram negative cell envelope
Thin peptidoglycan layer
Have inner and outer membrane, with peptidoglycan layer between, with space between
Immune system aprticularly primed to recognised compoents of grma negatiive cell wall
Pathogens incl. Escherichia coli, Salmonella enterica, Helicobacter pylori, Vibrio cholerae, Pseudomonas aeruginosa, Yersinia pestis
Gram-negative bacteria also have an outer membrane, located outside of the cell wall.
The outer membrane is partly composed of lipopolysaccharide (LPS), also known as endotoxin.
Lipid A is immedialey recognised as foregn, causes septic shock due to immune system overreaction
It is an integral part of the cell envelope and only released from dead bacteria that are broken down. It can cause endotoxic shock (immune response to endotoxin) during bacterial infections
preparation of gram stain
Spread culture over slide in thin film
Dry in air
Pass slide through flame to heat fix
Flood slide with stain, rinse and dry
Microscopy
Place drop pf oil on slide, examine with 100x objective
procedure of gram staining
Flood heat-fixed smear with crystal violet for 1 min
Result is all cells purple
Add iodine solution for 1 min
Result is all cells remain purple
Decolourise with alcohol briefly – about 20 sec
Gram positive cells are purple, gram negative cells are colourless
Counterstain with safranin for 1-2 min
Gram positive cells are purple, grams negative cells are pink/red
Gram-positive cells: dark blue or purple
Gram-negative cells: red or pink
The stain also enables determination of cell shape (e.g., Gram-positive rod, Gram-negative vibrio)
Acid-fast stain for mycobacterium species
Some bacteria dont stain withn gram stain, sometime need different stain more specific for thebacteria
Mycobacterium species (eg tuberculosis and leprae)nare detected with ziehl0neelsen acid-fast stain.
Acid-fast bacteria retain the bright red carbolfuchsin.
Non acid-fast bacteria stain blue.
acid-fast stain procedure
Stain with carbolfuchsin (red)
Decolourise with HCl/ethanol
Counter stain with methylene blue
This is important for these types of bacteria because they are important human pathogens (cause tuberculosis and leprosy respectivly)
Often slow growing in lab and present with other types of bacteria, so good to differentiate them
Acid-fast cell wall
Dont have outer membrane, more closely related to gram positive
Have thin peptidoglycan layer by instead have waxy coating made of mycolic acid
Capsules
Protective outer layer
Polysaccharide layers
May be thick or thin
May assist in attachment to surfaces or resist desiccation
Protect against phagocytosis (important virulence factor)
Therefore can prove much more deadly
Examples incl:
Mycobacterium tuberculosis,
Mycobacterium leprae
Even though protect bacteria, the capsules very good for vaccines since immune system not able to digest it, but if can recognize, is coated in antibodies and phagocytes can bind to it then digest
Pilli
Appendages that help in attachment
Pili are filamentous organelles found on the surface of some bacteria.
Pili are mainly used to attach bacteria to surfaces or to each other.
Bacteria can have two kinds of pili:
Long conjugation pili (also called sex pili). Involved in the transfer of genetic material.
Short attachment pili (also called fimbriae). These contribute to the pathogenicity of some bacteria.
flagella
Enable bacteria to swim
Particularly prevalent in food-bourne bacteria
Flagella are motility organelles expressed on the surface of bacteria.
They are long filaments that are rotated by a motor complex at the base of the structure.
Flagellated bacteria include:
Listeria monocytogenes, Bacillus cereus (Gram-positive)
Escherichia coli, Salmonella enterica, Helicobacter pylori, Vibrio cholerae, Pseudomonas aeruginosa, Yersinia pestis (Gram-negative).
flagella arrangements
Monotichous
eg vibrio choerae
Amphitrichous
eg campylobacter fetus
Lophotrichous
eg helicobacter pylori
Peritrichous
eg proteus mirabilus
Structure of gram-negative flagellum
Embedded in series of rings in cell envelope
Hollow tube powered through ATP
Has a hook
filament
– long outermost region surrounding a hollow core.
Hook
– curved, slightly wider than filament
Basal body –
anchors the flagellum to the cell wall and plasma membrane.
chemotaxis and movement
Chemotaxis= directed movement of cells towards attractive things and away from repulsive things
speed and direction of flagellar rotation results in various patterns of motility.
“Run” = movement in one direction for a length of time
“Tumble” = abrupt, random changes in direction; caused by reversal of flagellar Rotation
Motility enables movement toward a favourable environment or away from an adverse one. If the stimulus is a chemical, this is known as chemotaxis. Movement toward an attractant results in many runs and few tumbles – runs are longer when the concentration is increasing.
Peritrichous flagella
Counterclockwise rotation, cell runs
Flagella spread apart in clockwise rotation, cell tumbles
Random reorientation then counterclockwise rotation makes cell run in new direction
Polar flagella
Reversible flagella
Counterclockwise roation of flagella =run
Clockwise roation=cell reverse
Unidirectional flagella
Clockwise roation, cell runs
Roation stops, reoreitnation is random
Cw rotation, cell runs
Life processes carried out by bacteria require energy
Reproduction:
Synthesis of structural material for new identical daughter cells.
Differentiation:
Synthesis of new specialised cell types.
Communication:
Production of signal molecules, signal transduction
Self propulsion:
Flagellar biosynthesis, motility, chemotaxis
Metabolism supplies bacterial cells with energy; is the sum of all chemical reactions that occur in a cell
bacteria can be used for:
Can be used for:
Sewage treatment
Cyanobacteria remove harmful organic matter
Nitrogen fixation
Bacteria in soil makes atmospheric nitrogen assesible to plant and therefore to things that eat plant
Beverages and food
Can be cultivated for food use, eg fermentation
Drug productions
Virtually all antibiotics made from microbes, eg penicillin
Bacterial metabolism
The major elements C, H, N, O, P, S need to be assimilated into the cell, often against a concentration gradient.
The imported elements then need to be converted into the molecules that make up the structural components of the cell,
i.e., polymers of sugars, amino acids, and lipids, to enable cell growth.
This process requires energy
Catabolic and anabolic pathways
Pathways can be categorized as either catabolism or anabolism
Catabolism: break larger molecules to smaller ones
Produces energy and precursor molecules
Anabolism: combine smaller molecules to make more complex, larger ones
Produces macromolecules
Linkage:
Catabolic and anabolic reactions are frequently linked by energy. Catabolic reactions provide the energy needed for anabolic reactions.
Sometimes energy not enough, so Adenosine triphosphate (ATP) is a small molecule used to store or release energy
Catabolic pathways
Catabolic pathways break down macromolecules into simple component parts, releasing energy in the process.
These reactions release energy and are therefore exergonic.
AB → A + B
Anabolic pathways
Anabolic pathways build macromolecules by combining simpler molecules, using energy in the process.
These reactions require energy and are therefore endergonic.
A + B → AB
Microbial metabolism
Cellular respiration (oxidative phosphorylation)
- Aerobic
- Anaerobic
Fermentation (substrate level phosphorylation)
Photosynthesis Light Reactions (photophosphorylation)
Oxidation-reduction (redox) reactions
Oxidation = removal of an electron
Reduction = addition of an electron
Oxidation-Reduction (Redox) Reactions are always coupled.
Redox Reactions involve electrons being donated by an electron donor and accepted by an electron acceptor.
The oxidised/reduced form of an atom either side of a Redox reaction is known as a redox couple.
Aerobic respiration
The catabolism of glucose by aerobic respiration entails the complete oxidation of the carbon in glucose with oxigen as the terminal electron acceptor
the aerobic respiration of glucose occurs in the following stages:
Glycolysis
Krebs Cycle
Electron Transport Chain
Chemiosmosis
NADH and FADH2 act as electron carriers, citric acid cycle continues until acetyl CoA is used up, oxidative phosphorylation produces the most energy
Final electron acceptors for each type of respiration
Aerobic respiration, anaerobic respiration, and fermentation have different final electron acceptrs
Anaerobic respiration otherwise has same step.
Aerobic respiration uses oxygen, anaerobic respiration uses other biological moelcules
fermentation
Still undergoes glycolysis
One process by which pyruvic acid is subsequently metabolized in the absence of oxygen is called fermentation.
Fermentation results from the need to recycle NAD by passing the electrons of reduced NAD off to other molecules.
Two most common pathways are homolactic fermentation and alcoholic fermentation.
Neither captures energy in ATP; just removes electrons from reduced NAD to keep glycolysis going
Bacteria produce a range of fermentation end products
Lactic acid: cheese
Ethyl alcohol and co2 : wine
bacterial genetics
Bacteria are haploid organisms – they only have one copy of eachchromosome.
Bacteria usually have a single, circular chromosomes.
Bacteria may have plasmids in addition to a chromosome.
Bacterial dna replication
New strands of DNA are copied by the DNApolymerase enzyme in the 5’ → 3’ direction.
The process is initiated by an RNA primer.
The double-stranded helix opens apart to allow synthesis to take place.
One strand may be synthesized continuously (known as the leading strand). The lagging strand is synthesized discontinuously as Okazaki fragments.
As synthesis proceeds, the temporary RNA primers are removed and Okazaki fragments are joined together, resulting in a continuous new DNA strand.
Replication proceeds bi-directionally: both directions at once
DNA replication is semi-conservative – each new DNA molecule contains one strand from the parent
Genetic processes
Replication.
DNA makes new DNA
Transcription.
DNA makes RNA as the first step in protein synthesis
Translation.
RNA links amino acids together to form proteins.
Transcription and translation occur simultaneously in bacteria (as transcription occurs, mRNA is immediately translated to proteins)
Transcription
Transcription is the process where RNA is copied from the DNA chromosome.
It begins when RNA polymerase binds to the “start” (promoter) sequence
Transcription proceeds in the 5’ → 3’ direction, then stops when RNA polymerase reaches the “stop” (terminator) sequence
translation
Translation is the synthesis of proteins from a message RNA (mRNA) template.
The mRNA is translated in codons, a sequence of three nucleotides.
Each codon specifies a specific amino acid. Individual amino acids are carried in by tRNA molecules.
Translation of mRNA begins at the START codon, AUG, on the mRNA. Translation ends at a STOP codon (UAA, UAG, or UGA) on the mRNA
Bacteria readily share DNA with other bacteria
Transformation:
DNA is taken up from the environment.
Transduction:
Bacterial DNA is transferred via a virus that infects bacteria (phage)
Can sometime introduce host DNA to bacteria
Conjugation:
DNA is transferred between bacteria via a conjugation pilus.
DNA sharing between bacteria can mean antibiotic resistance, enabling bacteria to share genes allowing bacteria to hide from immune system etc
Bacterial Growth and Cell Division
Bacterial growth refers to an increase in number of cells, not an increase in size. (population increase)
Cell division in bacteria, unlike cell division in eukaryotes, usually occurs by binary fission.
During binary fission, a cell duplicates its components and divides into two identical daughter cells. (asexual reproduction)
The daughter cells become independent when a septum (partition) grows between them, and they separate
Binary fission
Symmetric cell division
Bacteria growth in liquid media
When bacteria are added to fresh liquid media, they normally go through four distinct growth phases:
Lag phase - numbers do not increase but bacteria are adapting to the medium.
Log phase (logarithmic or exponential growth) – highest rate of growth.
Stationary phase – cell division produces new cells at the same rate that old cells die.
Decline phase – cells die more rapidly than new cells arise due to depletion of nutrients or buildup of toxic waste products
Measuring bacteria growth
Direct cell counts
using a specialized microscope counting chamber
Turbidity measurement of bacterial growth
A liquid culture of bacteria has a cloudy appearance (turbidity).
Turbidity can be measured using a spectrophotometer.
Unscattered light is measured, giving readings in optical density
Viable cell counting
Colonies on a plate are counted – measuring a living, reproducing population. Dilutions ensure a countable number.
transmission
Passage of an infectious agent to a new host
Contact transmission
Direct contact
Eg animals bites
Indirect contact by fomites
(inanimate objects, buttons, rusty nail, etc)
Droplets
Eg from sneezes, sitting next to someone coughing
Airbone, faecal-oral
Waterborne
Airborne, incl dust particles
Foodborne
Vector borne
Biological
Lives part of life inside animal, transfers to another
Organisms taken up by vector and transmitted to next host
Mechanical
Eg flys pick up something from landing on rubbish etc, transmitt when land on something else
Steps in infection process
How many pathogen needed to start disease can vary widely depending on disease
Must be exposed to pathogen
Pathogen must adhere to skin or mucosa
Pathogen must invade through epithelium
Pathogen must be established: colonosation and growth oth pathogen
Must avoid/survive immune system
Pathogen can produce toxins to neutralise, kill immune cells
-Can be local effect or systemic
Invasiveness
-Pathogen invades past intial site of infection, spread to rest of body
Tissue damage
-Can occur both due to pathogen or due to immune response to disease
Time course for a ‘typical’ bacterial disease
Incubation period
Where pathogen is adhere and may begin to increase in numbers a small amount
May not be any symptoms
Can sometimes be contagious during this period, pathigen can find new hosts
prodromal phase
Pathogen detected by immune system
Produces some ‘flu-like’ vague symptoms, get sense are sick
Immune sysetm is activated
Invasive (Disease) phase
Symptoms become more severe, toxins being produced in high enough numbers to
– Acme
Peak of invasive phase, pathogen coutn is highest
– Fulminating
Term for when disease onset occurs very fast, acme is reached ra[idly (within hours)
Decline phase
If hsot survives, pathogen numebrs decline eitehr due to treatment or immuen response
Convalescence period
Repair/recovery period, fix tissue damage
Can sometime take a long time
Bacterial virulence mechanism for colonization and disease
Virulence facotrs increase bacteria's ability to infect
Bacteria must:
Avoid being killed by immune system (macrophages, complements factors)
Uses capsule
Flagella (inhibits phagocyte killing
Produces toxins which induce symptoms (enterotoxin
Endotoxin:
Something recognised by immune system as foreign, so immune system produced symptom (eg fever)
Sideophores
Proteins taht steal iron from host
Bacterial infections of the skin
Very few things can infect through intact skin, but are weak spots
Hair follicles
Abrasion, cuts to skin
epidermal layer has no blood access, prevent pathogen from entering blood
The skin for s a protective barrier to infection
the skin is the largest single organ of the body.
Skin surface consists of a thin epidermis and a thicker, underlying layer, the dermis.
The epidermis lacks blood vessels and is nourished by nutrients that diffuse from the dermis.
The epidermis has several layers of dead epithelial cells that function as a barrier against injury and infection.
The epidermis is renewed every 15-30 days.
Dead cells is important as viruses cannot infect dead cells
Cells contain keratin, a water-proofing substance.
Complex protein, very difficult to break down for bacterial enzymes
antimicrobial secretions of the skin
help limit pathogen growth
Sebaceous glands secrete sebum (lipids and organic acids)
Sebum helps maintain an acidic pH to discourage pathogen growth
The high salt concentration (from sweat glands) also inhibits many organisms.
microflora on the skin
The normal microflora is adapted to low pH and high salt conditions.
Resident bacteria exclude pathogens from colonizing but can occasionally cause infections too.
Common components of the skin microflora
– Staphylococcus epidermidis
– Staphylococcus aureus
– Propionibacterium acnes
– Pityrosporon ovale (a fungus)
staphylococcus aureus
skin infection
Staphylococcus: Gram positive, non-motile cocci
Eg Sty
Lesion due to bacterial infection atthe base of an eyelash
Folliculitis (pimple)
Lesion due to bacterial infection of hair follicle
Furuncle (boil)
Pus-filled lesions
Carbuncle
Massive pus-filled lesion
Scalded-skin syndrome
Caused by exfoliatin-producing strains of Staphylococcus aureus.
These toxins travel through the bloodstream and affect skin over much of the body.
The upper skin layers peel off on leaves. Most common in infants.
furuncle
Redness, tenderness, swelling are classical signs of inflammation.
Bacterial enzymes and pore-forming toxins cause tissue damage. In response, the host deposits fibrin, a tough fibre-like protein that forms a protective web.
The result is an abscess.
S. aureus remains trapped in abscess (therefore laregly stays local), limiting spread and damage. However, the bacteria are also protected from immunity and antibiotics!
Produces pus, mostly dead immune cells
Eventually some S. aureus may escape from the abscess if not treated
Typically need to be lanced and treated with antibiotics
Transmission and diesease of staphylococcus aureus
staphylococcus aureus colonises many healthy people.
Normally, S. aureus resides in the nasal passages. When it stays where it’s supposed to, it rarely causes a problem.
But S. aureus can cause opportunistic infections.
These occur when the microbe gets into a location where it doesn’t belong, i.e., in the blood, lungs, bones, or open wounds.
strains of staphylococcus aureus
the 1950’s, methicillin-resistant Staphylococcus aureus (MRSA) strains appeared and are now significant pathogens.
MRSA is resistant to methicillin, an antibiotic
the bacteria acquired a toxin that kills human immune cells
MRSA also acquired genes from commensal Staphylococci that made it more salt-resistant and hence more likely to be carried on the skin
Epidemic strains of S. aureus, on the skin, have led to increasing numbers of community-acquired MRSA infections.
Infections spread easily through skin-skin contact and pose a particular issue in contact sports.
streptococcis pyogenes
Has potential to be both skin and respiratory pathogen
Streptococcus: Gram positive, non-motile cocci
Causes:
Erysipelas:
Due to abrasions or surgery; begins as small raised lesions.
Caused by hemolytic streptococci.
Bacteria spread through the lymphatic system, form strong red lesions.
impetigo
A pus-producing infection which affects the face and other parts of the body. Also caused
by Staphylococci.
Necrotising fasciitis
Manifests as the death of large amounts of tissue due to the release of toxins.
Bacteria live on the dead tissue, producing more toxins. Amputation may be necessary
human respiratory system and infections
The average human breathes in approx 500 million litres of air in a lifetime.
The Human Respiratory System can be infected by a range of bacterial species
Indirect contact: airborne transmission
Very little barrier between alveoli and blood (due to need for gas exchange), weakness
Therefore important to ensure lower respiratory tract is protected from pathogens by upper respiratory tract (much more common than lower tract infections)
Pathogens can make us more likely to sneeze/cough, in order to spread disease to new hosts
Pathgens can live for horus on air (depending on size)
Upper respiratory tract
How does upper respiratory trcat protect the lungs>
Coarse hairs in the nose filter large dust particles from the air. The nose is lined with numerous mucus-secreting cells and ciliated cells.
The pharynx and trachea also contain mucus-secreting cells and ciliated cells.
The mucus moistens inhaled air and traps dust and other particles which may contain microorganisms.
The cilia move in synchronised waves and propel particles and microorganisms which have become trapped in the mucus upwards and away from lungs
this forms the so- called ciliary escalator which keeps the mucus blanket moving at a rate of 1-3 cm/hr.
Long term smoking severely imoacts ciliary escaltor, liekly to get smokers cought, which is another metohd of moving oathogens up
Normal microflora of upper respiatroy tracts
The normal microflora of the upper respiratory tract of healthy individuals contains pathogenic and non-pathogenic bacteria:
Haemophilus influenzae
Klebsiella pneumoniae
Neisseria meningitidis
Staphylococcus aureus
Staphylococcus epidermis
Streptococcus pneumoniae
Streptococcus pyogenes
Streptococcus pharyngitis (strep throat)
an upper respiratory disease caused by the group A Streptococcus species Streptococcus pyogenes.
Gram-positive cocci, nonsporulating, anaerobic, aerotolerant, homofermentative
S. pyogenes also causes other diseases, e.g., impetigo and necrotising fasciitis of the skin; otitis media of the inner ear.
Strep throat is characterized by local inflammation and fever. Enlargement of the tonsils and the lymph nodes in the neck can also occur
Streptococcus pharyngitis (strep throat) method
Most isolates produce streptolysins, toxins that lyse red blood cells.
On blood agar plates, this is seen as clear zones (a process known as β-haemolysis).
Some strains of S. pyogenes carry a lysogenic phage that encodes an endotoxin known as erythrogenic toxin.
This toxin produces a pink rash and damages small blood vessels and instigates a fever.
These symptoms are known collectively as scarlet fever.
S. pyogenes also produces a capsule.
Streptococcus pharyngitis (strep throat) symptom
Inflammation of the throat
Tonsils swell and can develop pus-filled lesions
Lymph nodes in the neck swell
Onset can be accompanied by chills, headache, nausea, and vomiting
Absence of cough or nasal discharge
scarlet fever symptoms
Pinkish red skin rash
Tongue has a spotted-strawberry appearance and loses its upper membrane and becomes enlarged
High fever
Diagnosis of strep throat
In addition to clinical symptoms and signs, diagnosis is based on Rapid Antigen Detection (RAD) systems.
A swab is taken of the patient’s throat
Surface antigens are extracted
S. pyogenes antigens are detected with an immunological assay using antibodies specific for S. pyogenes surface proteins.
Assays include Enzyme-Linked Immunosorbent Assay (ELISA), Latex-Bead Agglutination, and Fluorescent Antibody Staining.
Another diagnostic test involves in vitro cultivation of the bacteria from a throat swab.
Blood agar plates are examined for β- haemolysis – a clear zone on the plates that indicates streptolysin toxins.
strep throat treatment
Penicillin and its semi-synthetic derivatives are used for treatment.
Erythromycin can be used in individuals who have acquired penicillin allergies.
Strep throat currently remains relatively susceptible to penicillin antibiotics and its derivatives
Mycobacterium tuberculosis
Tuberculosis (Tb) is caused by the bacterium Mycobacterium tuberculosis.
Tb is one of the oldest recorded human diseases.
The bacteria were discovered by Robert Koch in 1882, for which he received the Nobel Prize.
At the time, 1 in 3 European adults died of tuberculosis (the “White Plague”)
M.tb characteristics
rod shaped
Acid-fast cell wall
Aflagellate
Long generation time (16-20 hr to double)
Capacity for ‘dormancy’
Obligate aerobe (requires oxygen)
Lacks ‘classical’ virulence factors (pili, flagella, or toxins)
Tb facts
About 1/4 of the world’s population – 2 billion people – are infected with tuberculosis. Most do not have any symptoms.
~5-15% of infected individuals become sick or infectious at some point. In 2025, over 10 million people fell ill with TB.
Concurrent infection with HIV greatly increases these odds (20-30 times).
Untreated persons with active TB can infect 10-15 people/year.
TB caused an estimated 1.23 million deaths in 2025. TB is the leading infectious killer.
Over 95% of deaths occur in low- and middle-income countries.
symptoms of tb
Contracted via aerosols
Primary site of disease=lungs
Symptoms:
Persistent cough
Loss of appetite
Weight loss
Fevers
Night sweats
constant tiredness
Disseminated tuberculosis:
Bacteria can spread beyond the lungs in active Tb
Disease can spread to brain, GI tract, lymphatic, genitourinary tract, bones
treatment of tb
Prevention:
live BCG vaccine
variolation
Diagnosis
microscopic and culture examination of sputum samples
- Most common/standard
X-ray
-Cloudy area shows tubercule; immune response trying to contain infectious agent
tuberculin-skin test
-Tests if someone has been previously exposed (not exclusive to infection, can have had the be cured, or have been vaccinated)
- Positive test is red lesion at injection site
PCR
cytokine profile
Intervention
surgery
antibiotics: isoniazid, rifampin, pyrazinamide, ethambutol, streptomycin
Uptake of mycobacterium tuberculosis
When the Mtb reachs the lung in aerosol droplets, the bacteria are phagocytosed (eaten) by resident macrophages.
Mtb inhibits phagosome-lysosome fusion - the bacteria survive inside the macrophage.
Infected macrophages release cytokines, attracting other immune cells.
The cells fuse to form a granuloma (tubercle) that contains the bacteria.
Mtb can survive indefinitely in a granuloma.
Infection cycle of Mycobacterium tuberculosis
For 90% of patients, bacterial replication stops once a granuloma has formed in the lungs.
This is latent tuberculosis (patient feels fine).
In ~10% of cases, the bacteria replicate, and active tuberculosis develops.
People with latent TB can develop active TB later in life.
Immune suppression, smoking, and HIV infection increase the risk of active TB
Active TB is very contagious, bacteria can disseminate beyond the lungs
granuloma
the pathogen is encased in and contained by immune cells.
Mycobacterium tuberculosis Treatment
Starts with a combined therapy (if take one, likely to develop resistance)
- Isoniazid
- Rifampin
- Pyrazinamide
- Ethambutol or streptomycin
Regimen may be adjusted when drug susceptibility results are known.
Total treatment time = 8 weeks of 4 drugs + 16 weeks of 2 drugs = 24 weeks total
Mycobacterium tuberculosis: The other drug problem
TB patients often fail to take full course of prescribed medication.
TB course of treatment is long
Many pills have unpleasant side effects
Many patients stop taking pills when they start to feel better
More susceptible bacteria are killed quickly… more resistant bacteria persist and proliferate.
Multi-drug resistant TB (MDR-TB): resistant to at least two of the optimal drugs for treating TB (“first line”).
Extensively drug resistant TB (XDR-TB): resistant to at least four drugs for treating TB (“first and second line”).
Solution:
Directly Observed Therapy, Short Course (DOTS)
Health care worker watches patient swallow each dose of medication.
Improves adherence, reduces relapse and acquired drug resistance.
Cures TB 80% of the time.
DOTS is widely used in New Zealand too
Bacterial Infections of the Gastrointestinal Tract
The GI tract enables us to ingest food for energy.
Bacteria are introduced at the same time in food and water.
On average, ~8 x 1010 microbes are consumed each day.
Our large intestine is also home to about 1014 resident bacteria.
These bacteria colonise shortly after birth.
They play a key role in our health.
Metabolism
Gut development
Immune development
Protection from disease
Introduced via food and water
Mouth
Many resident microbes, including teeth biofilm
Stomach
Extremely acidic kills most bacteria. Few resident microbes
Small intestine
Digestion aided by secretions from liver and pancreas.
Most digested food absorbed here.
Large intestine
Many resident microflora.
Anaerobic, so microbes mainly ferment.
indigestible fibre metabolised, beneficial products made
Streptococcus mutans and Disease of the Mouth
eat sugar—> breaks down into glucose and fructose. glucose is fermented by bacteria, (becomes dextrans: cemenst bacteria to tooth). fructose becomes lactic acid (eats away tooth enamel)
cause tooth decay and periodontal disease if untreated