BIOL 2044 - GI Infections

biofilms

• 80% of infections caused by biofilms

• cant study an organism in isolation - must be studied in the community they live in

• found in

  • implants

  • mouth

associated complications with biofilms

ASSOCIATED MEDICAL PROBLEMS

• dental plaque

  • leads to odour, tooth decay, gum disease

• stomach intestine colon infection

  • can cause gastroentiritis —> E. coli, C. diff, H. pylori

• upper respiratory infections

  • can cause cystic fibrosis —> P. auruginosa

• biofilms on heart valves

  • can cause endocarditis —> strep

• urethra/cervical infections

  • can cause gonhhorea, cyphilis —> gonococci, candida

• bone diseases

  • can cause deep seated abscess —> caused by staph, streptococci, bascillus

oral cavity

• succeptible to

  • bacteria

  • fungi

  • mycoplasma

  • protozoa

  • viruses

• normal, healthy bacteria

  • streptococci

  • lactobacilli

  • staphylococci

  • corynebacteria

  • anaerobes

• dental plaque forming on the gum margin can lead to

  • dental caries

  • gingivitis

  • peridontitis

host interaction with microbe

• equilibrium between endogenous bacteria and oral defence system

1. PHYSICAL BARRIER

• keritanised epithelium

• mucin production

• salivary flow

2. CHEMICAL COMPOUNDS

• salivary enzymes

• antibacterials

• gingival fluid secretions

3. INFLAMMATORY REACTION

• bacteria produce a range of molecules sensed by other bacteria which helps to recognise commensal bacteria from pathogens

acquisition of oral flora

• at birth: sterile

• within hours: streptococcus, S. salivarius —> acquisition of oral flora depends on time of birth, pre/post partum, caesarian, vaginal, who handles the baby

• by one year old:

  • streptococcus

  • lactobactilli

  • neisseria

  • staphylococci

  • fusobacterium

  • actinomyces

• when teeth first appear, initial colonisation is by streptococci, Mutans, streptococci Sanguis on the teeth and in gingiva

• other streptococci adhere strongly to gums and cheeks but not the teeth

• colonisation of crevaces of the teeth tend to be prevotella (an anaerobe)

• a loss of microflora as teeth are lost —> 2nd childhood microflora

• organisms acquired reflect the surfaces to which they can adhere (dramatic shift between enammel and dentures)

bacteria in oral cavity

• 10^8 bacteria a shed

• >300 species from dental plaque, 5% of salivary flora

• 1mg of plaque contains 10^6 flora

• flora of healthy gingiva is mostly fulcatative anaerobic bacteria and aerobic bacteria

• >40% of oral cavity is unculturable

dental caries

• due to a high sugar diet and poor hygeine

• holes in teeth, malodour

plaque

• formed by long filamentous structure surrounded by bacteria (bacterionema maturococci and strep sanguis) —> gives corn cob shape

• strep sanguis forms lactic acid and the maturococci converts lactic acid —> butyric acid

• interact with eachother

plaque forming bacteria

STREPTOCOCCUS

• sacrolytic —> metabolise sucrose and other sugars

• glucosyl transferases —> cleaves sucrose into either soluble glucans or insoluble mutans

• fructosyl tranferases —> adds a fructose to a growing fructan or makes inulin (insoluble) —> broken down into glucose

• acidogenic bacteria ferment glucose into lactic acid, formic acids which lower pH

• aciduric bacteria grow at low pH —> plaque adjacent to ennamel has low pH (4) which decalcifies hydroxyapatite enamel

OTHER SPECIES IN PLAQUE:

VEILLONELLA

• gram -ve anaerobe

• thrives in acidic environment of caries and is thought to slow development of caries

• converts lactic acid of other species to less acidic products

LACTOBACILLUS

• gram +ve

• grows aerobic and anaerobically

• found symbiotic in gut but in the mouth is a sign of development of caries

peridontal disease

can either be non destructive gingivitis or can be destructive peridontitis

1. non destructive gingivits

   • poor hygeine

   • inflammed and bleeding gums

2. destructive peridontitis

   • usually get as older unless very poor dental hygeine

   • gum and bone loss

gingivitis

FUSOSPRIOCHETES

• spirochetes and fusiform bacteria live in normal flora and in mouth

• in case of bleeding oral cavity bacteria can cause infection which leads to oral cavity

• diseases include:

  • acute necrotizing ulcerative gingivits referred to as trench mouth

  • caused by prevotella fusobacterium, traponella borella

peridontitis

TERONEMA DENTICOLA

• spiral shape bacterium

• gram -ve

• elevated in people with disease

• motile, highly proteolytic

• contributes to destruction of tissue

PORPHYROMONAS GINGIVALIS

• gram -ve anaerobic bacteria

• found particularly in chronic forms

AGGREGATIBACTER ACTINOMYCETEMOMITANS (AA)

• gram -ve

• facultative rod

• aggressive preidontitis in young patients

• produces leukotoxins which kills PMNs and monocytes, cytoskeletal distending toxin, immunosuppression factors that inhibit blastogenesis

• antibody production and active supressor cells

• anaerobic metabolism: protein degradation and ammonia (provokes immune response and contributes to tissue destruction)

measuring species interaction

• can culture bacteria together and see if they form coaggregates

• primary species - bind to salivary proteins (the acquired pellicle)

• the secondary bacteria bind to pioneer species (vionella) but cant bind acquired pellicle

• tertiary colonisers cant bind to acquired pellicle or pioneer species

cell cell communication

• cell cell signalling molecules used for quorum sensing

• intra species communication —> gram negative bacteria produce small peptides which help promote stimulating peptodes which help promote single species biofilm formation

• inter species: 4,5 dihydroxy 2,3 pentadione also called autoinducer 2

• stimulate plaque formation and virulence determination

anti pathogen strategy

• can control but not eliminate biofilm

• attempts to kill coloniser species such as fusobacterium

• human microbiome project attemot to sequence genome of the microbiome rather than culturing

microbial colonisation

• helicobacter pyori: can get inti stomach and penetrate mucous lining —> protected from immune system and decreases competition with other cells

• produces urease which neutralises acid

• causes stomach ulcer and can also cause cancer

• produces vaculating cytotoxin A which kills cells in lining of teh stomach and allow bacteria better access to nutrients

• kills the cells that they invade and creates holes in the stomach lining —> forms ulcers

• TLPA ad TlpD genes are acid sensors and causes bacteria to swim away from acid (mucin layer has a gradiet pH)

• urease bacteria convert H2O and (NH2)2CO —> HCO3- + NH4+

• NH4+ helps to neutralise acid and facilitate survival

intestinal flora

• contain lots of microbial cells

• 100x as many microbial genes as host

• colon bacteria = 60% of dry mass of feaces

• bacteria in colon form biofilm like layers and high cell density which promotes quorum sensing

• many bacteria are anaerobic but aerobes in calcum close to anus

early gut microflora

• colonise with large no of E. coli and streptococcus

• within days create environment favourable for bfidobacterium, bacteriocides, clostridium, rhuminococcus

• breast fed babies become dominated by bfidobacterium which is beneficial to development of babies

mature gut species

• bacterodietes —> 1/3 of all bacteria

• clostridium, fusobacterium

• rheuminococcus

• bfidobacterim —> beneficial all throughout life

• people have tried to generalise communities to 3 types

  • T1: high bacteroides

  • T2: prevotella common and low bacteroides

  • T3: high levels fo rheuminococcus

• commesnal coexistance

• organisms use fermented unused energy substrates

microboime health dysbiosis relationship

• different axes can lead to different conditions

• continual effect on gut/immune system between pathogens and commensal bacteria

• 3 main innumosensory cells:

  • m cells

  • dendritic cells

  • surface enterocytes

• PRRs include:

  1. toll like receptors

  2. nucleoside binding oligomerisation domains/caspase recruitment domain isoforms

     • cytoplasmic proteins which recognise endogenous proteins/stress response from community

     • leads to activation of NFKb signalling molecules if we enter dysbiosis

PSA: polysaccharide

• key olecule

• capsular polysaccharide which resembles hairs on a kiwi fruit

• 2 of 8 polysaccharides have zwitterionic structure essential for modulating the immune system

• PSA restores CD4 t cell levels

• mutant bacteria lacking PSA doesnt restore t cells and generates inflammatory response

  • inbalance of TH1 cells which moves to TH2 cells

  • leads to inbalance between B and T cells

• production of IL4 and IFN gamma which causes imbalance, PSA helps restore this

• IL17 potent inflammatory cytokine associated with autimmunity

• adding B fragilis bacterai you can dampen the immune response 8

gut flora repress pathogens

• gut floar can prevent harmful effects from competitive exclusion

• overgrowth of C. diff can cause pseudoembranous colitis but can be prevented by exclusion of bacteria

• can be done by fecal transplant