Commensal bacteria vs Pathogens

what is the microbiota?

collection of microorganisms that live in and on the human body

what is dysbiosis?

alteration in the normal composition of the microbiota (particularly in the gut) where harmful microbes may overgrow and outnumber beneficial ones

what diseases can result from dysbiosis?

• inflammatory bowel disease → UC and CD

• liver diseases e.g. cirrhosis

• type 2 diabetes

• cancers

• heart diseases e.g. hypertension

in what ways is the microbiota utilised in disease treatment?

• probiotics: live beneficial bacteria that help restore or maintain a healthy balance of gut microbiot

• diet → pre and postbiotics

• engineered bacteria

• bacteriophage therapy

• faecal microbiota transplantation

• live biotherapeutic products: similar to probiotics but often more specifically designed for targeted treatments

what is a symbiotic association?

close relationship between two different species where at least one benefits from the interaction → other may benefit, be harmed, or remain unaffected

what are the 3 types of symbiotic associations?

• mutualism

• commensalism

• parasitism

what is mutualism?

relationship where both organisms benefit from the interaction

• e.g. in the gut, certain bacteria help in the digestion of food while the bacteria receive nutrients from the host :. mutually beneficial relationship

• often metabolically dependent on each other to some degree

what is commensalism?

one symbiont (commensal) benefiting from the relationship while the other (host) is neither helped nor harmed → they are unaffected

• e.g. bacteria on human skin → bacteria gain nutrients from sweat and oils while humans are largely unaffected

what is parasitism?

one organism benefits at the expense of the other

• e.g. parasites like tapeworms in the human intestine gain nutrients from the host while causing harm to the host → disease or malnutrition

are symbiotic relationships static?

no → dynamic

• under certain conditions they can shift from their natural nutritional form to another e.g. mutualist may become parasitic under certain conditions

what is the difference between infection, disease, colonisation and asymptomatic disease?

• infection: occurs when a pathogen enters and multiplies within a host → can potentially causing harm → may or may not lead to noticeable symptoms.

• disease: condition where the infection causes observable symptoms or damage to the host → results from pathogen disrupting the normal function of the host's body

• colonisation: presence and growth of microorganisms on or within the body without causing disease

• asymptomatic disease: state where a person is infected with a pathogen and may even carry the disease but does not exhibit symptoms → pathogen can still be transmitted to others.

why is asymptomatic disease a public health issue?

• pathogen can still be transmitted

• can cause disease in others unknowingly

why is the skin’s microbiome beneficial?

protect the skin by outcompeting potential pathogens for resources, producing antimicrobial substances, and modulating the immune system to prevent inflammation

which areas of the skin have a favourable environment to support commensals?

• sufficiently moist regions like scalp, palm, ears, genital regions

• many are associated with glands which can provide them with nutrients

what properties of the skin prevents commensal organisms from overgrowing and becoming infectious? (5)

• limited nutrient availability: skin’s surface is relatively dry and nutrient poor :. limits the resources available for bacterial growth → restricts their ability to multiply excessively

• acidic pH: The skin's acidic pH (around 4.5 to 5.5) creates an environment that inhibits the overgrowth of bacteria

• antimicrobial compounds: skin produces antimicrobial peptides (AMPs), fatty acids, and other inhibitory substances through sweat and sebum → these compounds have broad-spectrum antimicrobial activity that helps keep bacterial populations in check :. prevents overgrowth

• desquamation: constant shedding of dead skin cells (desquamation) helps to remove bacteria from the surface → natural exfoliation reduces the chances of bacteria establishing large colonies or overgrowing on the skin

• immune system surveillance: skin is home to various immune cells such as T cells which monitor and respond to pathogens or imbalances in the microbiota

give examples of commensals associated with the skin

• Staphylococcus epidermis

• Propionibacterium acnes = most prevalent bacteria associated with skin glands (gram negative anaerobe)

describe the nature of the microbiome in the respiratory tract

• upper respiratory tract (nose, throat, and sinuses) is home to a wide variety of bacteria, with Streptococcus and Staphylococcus species being most abundant → can be pathogenic but part of normal microbiome because they lack virulence factors :. lower potential to cause disease

• lower respiratory tract (lungs and bronchi) typically has fewer microbes due to the mucociliary escalator and immune defenses that clear foreign particles and pathogens

• microbial community in the respiratory tract is shaped by factors such as age, diet, environmental exposures, and health conditions like smoking or asthma

how do organisms part of the normal microbiome in the oral cavity resist mechanical clearance?

have virulence factors that allow them to adhere to tongue, teeth, gums etc

what prevents the overgrowth of commensals in the respiratory tract microbiome?

lysosomes in mucus → hydrolyse the peptidoglycan layer :. break down bacterial cell walls

what are the 3 sections of the small intestine?

• duodenum

• jejunum

• ileum

describe the microbiome in the GIT

• stomach and duodenum: few microbes due to acidic environment and digestive enzymes

• jejunum: more diverse microbiome than the duodenum due to the higher availability of nutrients including carbohydrates and proteins → but less than ileum

• ileum: most diverse and densely populated microbiome in the small intestine because environment is most similar to colon

• colon/large intestine: more favourable environment → neutral pH, nutrient availability, moisture, temperature :. most diverse microbiome in GIT

give examples of organisms in the microbiome of the GIT

• streptococcus

• staphylococcus

• enterobacteria

what influences the gut microbiome?

• diet: rich in fibre, plant-based foods, and fermented products promotes the growth of beneficial bacteria → high-fat and high-sugar diets can encourage the growth of harmful bacteria or reduce diversity in the microbiome

• antibiotic use: can kill harmful and beneficial bacteria

describe the microbiome of the genital urinary tract

• upper GU tract (kidneys, ureter and bladder) have a low diversity of bacteria

• vagina is predominantly colonised by Lactobacillus species → produce lactic acid and hydrogen peroxide :. maintains a low pH (around 4.5) that inhibits the growth of harmful pathogens

what affects the microbiome in the GUT?

vaginal microbiome is influenced by factors such as:

• age

• hormonal fluctuations (e.g., menstruation, pregnancy, menopause)

• antibiotic use

• sexual activity

• hygiene practices

define virulence

ability of microorganism to cause infection i.e. pathogenicity

what is koch’s postulates?

set of criteria on how to prove is a pathogen is responsible for disease:

• organism must be found in all hosts with disease

• organism must be isolated in pure culture

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

• organism should be re-isolated into pure culture from intentionally infected host

what are the reasons as to why it may not be possible to prove Koch’s postulates?

• ethical: not always possible to infect a healthy host

• biological: when re-isolating, virulence can be lost on culture

what is the molecular version of Koch’s postulates? (6)

more focussed on genes/products that give pathogenic potential rather than identity of organism causing disease→ new criteria:

• genes or their products have pathogenic potential

• gene should be found in all pathogenic strains but not in avirulent strains

• disruption of the gene should reduce virulence

• avirulent strains can be transformed into virulent strains by cloning the gene

• gene must be expressed during infectious process

• gene product should elicit an immune response in patients that are not immunocompromised

what are the 2 means of transmission of pathogens?

• direct contact from host-host by coughing, sneezing, and body contact

• indirect → vectors or fomites

how do vectors indirectly transmit pathogens?

• biting

• urine

• faeces

• bodily fluids

what are fomites?

inanimate objects or surfaces that can carry and transfer infectious microorganisms

• phones

• food

• water

• dust

• sewage

why is adhesion of microorganisms important?

• when microorganism reaches host surface, it needs to adhere to be able to colonise the area

• important for mucosal surfaces which are washed by fluid e.g. mouth

what are the 2 strategies of adhesion that microorganisms use?

• pili

• formation of biofilms

describe the nature of pili in microorganism adhesion

• rod shaped protein structures that mediate attachment → ordered helical bundles which extend out to establish contact

• binding is very specific :. location of available receptors determines where microorganisms will colonise

• fragile → constantly being reformed to evade host immune response → once antibodies bind to pili, adhesion can no longer occur

describe the nature of biofilm formation in microorganism adhesion

• microorganisms adhere to surfaces and produce an extracellular matrix that protects them from environmental stresses and antimicrobial agents :. remain attached and proliferate

• matrix is composed of polysaccharides, proteins, and DNA

• biofilms can form on both biotic and abiotic surfaces

• in handling of urinary bags and catheter tubing, microorganisms can be introduced → may form biofilm on plastic surface :. potential to enter the body

why is colonisation of mucosal surfaces difficult?

bacteria can be cleared by mucosal layer

how has bacteria evolved to induce their uptake by non-phagocytic host cells?

can induce cells that aren’t normally phagocytic to facilitate microorganism uptake inside them

• microorganism has invasin virulence factor which causes cytoskeleton rearrangement in host cells → causes actin depolymerisation :. microorganisms can enter the cell

• once bacteria has been engulfed by the host cells, it again interacts with actin to escape the phagosome by degrading the lipid membrane or forming pores

• bacteria must escape phagosome before fusion with lysosome otherwise it can be degraded by lysozymes

what is needed for the growth and multiplication of microorganisms? how is this retrieved?

• need free iron

• concentration of free iron is low → haemoglobin bound

• siderophores are secreted → this picks up iron

• siderophore-iron complexes are then recognised by specific receptors on the bacterial cell surface and transported into the bacterial cell via specialised uptake systems

• complex is cleaved :. iron is now free to use

• endotoxins can also release bound iron :. will kill host cell and sequester its free iron by haem binding proteins

how do pathogens evade immune response?

virulence factors

• capsule = network of polysaccharide that covers the surface of some bacterial pathogens :. prevents activation of complement pathway :. reduces phagocytic killing

• endotoxins can kill phagocytes, inhibit their migration or reduce their strength