commensal bacteria vs pathogens

what is symbiosis?

the interaction between two different organisms living in close physical association

what are the 3 different types of symbiotic associations?

compensation

mutualism

parasitism

what is communalism?

o   where one of the organisms (the commensal) benefit whereas the other (the host) does not benefit but is also not harmed

§  The host may other nutrients or shelter to the commensal

§  The commensal is not directly dependent on the metabolism of the host so if they are separated, the commensal can survive

what is mutualism?

o   both species, the mutualist and the host, both benefit

§  Both parties depend on the metabolism of the other

§  Eg lichens on trees

what is parasitism?

where the host dies or is harmed due to the parasite

what is infection?

-              when a microorganism that can cause disease becomes established in the body

o   Infections do not always lead to disease

what is disease?

-              an infection that produces symptoms

what is persistence?

colonisation of an infection without causing symptoms

what is asymptomatic carriage?

If the host does not cause disease for a long time and remains dormant

describe the microbiome of the skin

-              The epidermis (top layer of the skin) is not a favourable environment for the skin

o   The periodic drying of the epidermis makes a lot of colonies dormant

o   The scalp, behind the ears, the palms and genital regions are sufficiently moist to support commensals

§  The epidermis in these regions have a slightly acidic pH due to oil and sweat secretions

§  Sweat also contains NaCl, giving it osmotic properties

o   However, the skin also produces inhibitory compounds such as lysozymes, which helps to control commensal colonisation, preventing overgrowth and infection

which part of the skin layers do bacteria prefer?

-              Most skin bacteria are associated with glands, which provides nutrients eg sebaceous glands

o   Eg staphylococcus epidermidis – an anaerobic gram-positive cocci bacterium

o   Eg Propionibacterium acnes – the most closely associated to skin glands

§  Is a gram-positive anaerobe

describe the microbiome of the nose

-              The colonies are mostly found in the nose

-              Staphylococcus epidermidis

-              Staphylococcus aureus – gram positive cocci bacteria

-              Both are found in approximately equal numbers

-              Approximately the same number here to the epidermis/skin

describe the microbiome of the nasal pharynx region

o   Staphylococcus pneumoniae – in small numbers and is a lancet shaped bacterium

o   Neisseria meningitidis – gram negative cocci

o   Haemophilus influenza – anaerobic gram-negative cocci

o   Although these disease-causing bacteria occupy the nasal pharynx region, they lack the capsule virulence factors to cause symptoms and hence disease

o   They are carried as commensals in the nasal pharynx

describe the microbiome of the ortho pharynx region

lpha Haemolytic Streptococci – gram positive cocci

describe the microbiome of the respiratory tract

-              doesn’t usually have a normal microflora/microbiome as they are readily removed by mucociliary action and phagocytic action

-              Lysozymes present in the mucus also have an antibacterial effect

Describe the microbiome of the oral cavity

o   The bacteria present here can resist being cleared by these mechanisms by adhering to the gums, teeth and tongue via their virulence factors

o   The initial microbiota after birth is colonised by:

§  Actinomyces

§  Streptococcus

§  Lactobacillus

§  Neisseria

§  Yeast

o   Once teeth start to appear, the bacteria colonies that dominate become anaerobic:

§  Streptococci – which can attach to the buccal and other epithelial surfaces and can also colonise the saliva

·      This can contribute to dental plaque, caries, gingivitis and periodontal disease

·      These are commensal organisms, but if they overgrow, they can become pathogenic

Descrie the microbiome of the GIT

-              Most microorganisms are killed by the stomach acid

-              The organisms that survive (less than 10 colony forming units/ml):

o   Lactobacillus

o   Pepto streptococcus

o   Yersinia

o   Yeast – candida

when does the number of bacteria in the GIT increase?

increases during a meal then begins to drop as the gastric acid kills them off

what happens to the microbiome if there is a blockage of the intestine?

-              (eg due to intestinal obstruction, causing duodenal reflux) can cause an increase in pH in the stomach

o   This would then cause the microbiota of the stomach to reflect that of the ortho pharynx

Alpha Haemolytic Streptococci– gram

describe the microbiome of the small intestine?

-              divided into three areas the duodenum, jejunum and ileum

o   Duodenum – contains few microorganisms due to gastric acid secretion and bile secretion from the pancreas

o   Jejunum – gram positive rods and cocci are dominant

o   Ileum – similar microbiota to the colon

§  Gram negative bacteria

§  Enterobacteria

describe the microbiome of the colon

-              10-12 colony forming units per gram wet weight of faeces

o   Enterobacteria faecalis

o   Bacteroides

o   Bifidobacterium

o   Eubacterium

o   Peptococcus

o   Pepto streptococcus

o   Ruminococcin

o   Clostridia

o   Lactobacilli

o   Streptococcus

o   Staphylococcus

o   Non-spore forming bacteria, yeast and protozoa may occur as harmless commensals

what influences the presence of certain bacteria of the GIT?

diet

o   Eg the presence or absence of bifidobacterium and lactobacillus is dependent on the feeding of newborn infants

-              The microbiota can also be affected by disruptive factors such as the use of antibiotics such as penicillins

describe the microbiome of the Genitourinary tract

-              Upper GU tract (kidneys, ureter, bladder) are usually sterile

-              Only a few genera are present in the urethra

o   Staphylococcus epidermidis

o   Enterococcus faecalis

-              The female GU tract has a very complex microbiota due to large surface area and can also change throughout the menstrual cycle

o   Most dominant is the acidic tolerant lactobacilli

§  These ferment glycogen, which is secreted by the vaginal epithelium, forming lactic acid

§  This maintains the pH of the vaginal and cervix (~4.5-4.6)

define virulence/pathogenicity

-              the ability of a microorganism to cause infection

define virulence factor

-              – a product or strategy that contributes to virulence

o   Promotes colonisation or invasion of the host

o   Can damage the host

what is koch’s postulates used for?

-              postulates show whether it is a particular pathogen that causes a particular disease

what are koch’s postulates?

o   The organism must be found in all hosts with the disease

o   The organism must be isolated in pure culture

o   The organism should produce the same disease when inoculated into a healthy host

o   The organism should be re-isolated in pure culture

what are some drawbacks of koch’s postulates?

-              that virulence is independent of the host and is dependent only on the microbial

o   However, if a patient is immunosuppressed, it does render them more susceptible to infection

o   Also it is difficult to isolate many microbials on lab media

o   For ethical reasons it is not always possible to inoculate a healthy host

o   Virulence can be lost upon re-isolating

what is the molecular version of koch’s postulates?

o   Genes should be found (or their products) as they have pathogenic potential

o   Gene should be found in all pathogenic strains but not in avirulent strains

o   Disruption of the gene should reduce virulence

o   Avirulent strains can be transformed into virulent strains by cloning the gene

o   The gene must be expressed during the infectious process

o   The gene product should elicit an immune response in individuals who are not immunosuppressed

how can a pathogen be spread?

o   Via direct contact from host to host (coughing, sneezing, body contact)

o   Indirect transmission (eg by a vector, parasites in faeces, urine or bodily fluids)

o   Fomites – innate objects that harbour and transmit pathogens (eg food, water, dust, sewage)

how does adhesion and colonisation of the host occur?

o   Particularly important in surfaces such as GIT, urinary tract, mouth and mucosal surfaces

o   Occurs via pilli and adhesions – pilli consists of helical bundles of protein deposits

how do the pills cause adhesions?

§  These structures extend outwards to develop contact between cell surfaces and the host cell surface (carbohydrates or glycolipids)

§  The binding of pilli is very specific so the availability of their specific receptors will determine the site and size of colonisation

§  Pilli are constantly being reformed because they are fragile and easily damaged

what is the drawback of the pill being constantly replaced?

§  As these are fragile and they are proteins, they are constantly mounted on by the body by antibodies

·      But because they are constantly replaced, the chance of an immune response occurring is greatly reduced

·      Once antibodies have bound to the pilli tips, it is impossible for adhesion to occur

Eg UTI, STI’s such as gonorrhoea

how is the problem of fragile pilli overcome?

§  Some microorganisms have structures that facilitate much tighter binding after the pilli have bound (little is known about these afibrial adhesions)

·      Eg protein F on streptococcus pyogenes that mediates attachment to fibronectin

what are biofilms?

o   Another mechanism of adhesion is through the formation of biofilms

§  The formation of dense and multi-layered surfaces

§  The first layer attaches directly to the substratas

§  The other layers are attached to the basal layers by a polysaccharide matrix (eg dental plaque or pseudomonas aeruginosa in cystic fibrosis patients)

§  Also important when dealing with urinary catheters as microorganisms can be easily introduced and these can cause biofilms

how do antibodies protect against pathogens in mucosal layers?

-              Pathogens planning to cause infections have to find a way to not be trapped in the mucus/mucin layer

IgA/secretory antibodies bind to bacterial antigens and interact with mucin by Fc receptors on bacteria

how can bacteria colonise mucosal surfaces?

-              Bacteria can however produce proteases, which cleave IgA

o   Most proteases cleave IgA1, which is the most predominant isotope found on mucosal surfaces

how can host cells take up pathogens?

o   This is done by changing the structure of the cytoskeleton of the host cell (actin depolymerisation)

o   The surface proteins that provoke cytoskeleton rearrangement are called invaslings

o   Once bacteria has been ingested, it interacts with actin to free itself from the phagosome by degrading membrane lipids or by forming pores

o   It is important for bacteria to escape before the fusion of lysozymes to the phagosome (this is a defence mechanism that some cells have to kill or destroy invading pathogens)

what is a key metal needed for bacterial growth?

-              Iron is essential for bacterial growth

-              Free iron is limiting in natural environments especially in the human body as it is normally bound

how do siderophores aid bacterial growth?

-              Siderophores (has 2 classes catechols and hydroxamates) chelate or free up free iron with high specificity

o   Siderophores are secreted then bacterial cells take up the siderophore complex

o   Inside the cell, the complex is cleaved, releasing free iron

how do exotoxins aid growth of bacterial cells?

-              Exotoxins can release bound iron from cell at low iron concentrations

o   These kill host cells, releasing bound iron

o   The bacterial cells can then take up the iron via ferritin or haem binding proteins

what is the capsule and what is it’s role?

-              – a network of polysaccharide polymers that cover the surface of some bacterial pathogens

o   The role of the capsule in pathogens is to evade the complement activation and phagocyte mediated killing

describe the complement activation

o   Assembly of the C3 convertase

o   Some capsules can prevent the formation of C3 convertase by failing to bind serum protein B

o   Other capsules have higher affinity to serum protein H than B

o   If the C3B complex binding with factor H occurs instead of B, it is degraded by serum protein H

o   By preventing C3BB formation, the capsule is likely to be optimised by C3B, making the cell less likely to be engulfed by phagocytes

o   Less C3B convertase formation means less C5B will be produced, so less likely for a membrane attack complex will form on the membrane

o   In basic terms, the normal immune response is to form a membrane complex which results in cell and pathogen destruction, but these capsules can prevent this from occurring, essentially hiding the cell from the immune system

what is special about some capsules?

they can resemble the host polysaccharides

how can some bacteria avoid complement activation?

-              A bacterium that specifically degrades C5a (the chemoattractant for phagocytes) has been described in Staphylococcus pyogenes

what are some anti-phagocytic strategies of bacteria?

-              Some bacteria can produce toxins that kill phagocytes, inhibit migration or reduce the strength of oxidative burst

-              Some toxins can prevent phagocytic recruitment to the loci of the infection but also prevent phagocytes that do not reach the sites of the infection

how can some bacteria survive inside phagocytic cells?

o   Can escape the phagosome

o   Prevention of phagocyte lysosome fusion

o   Reduced effectiveness of phagosome killing (resistance to killing by defensins, reduced production of catalase superoxide disputase, detoxifying reactive forms of oxygen, cell surface polysaccharides that detoxify oxygen radicals and refractory cell walls)