IMED2001 - Medically important gram positive bacilli (L4)

Classification of Medically Important Gram positive bacilli

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- They can be endospore formers or non endospore formers

- non endospore formers can be regular shape and staining or irregular shape and staining

- irregular shape and staining can be non-acid fast, acid fast or filamentous

- endospore formers that are aerobic are called bacillus

- endospore formers that are anaerobic are called clostridium

Medically Important Bacteria

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Important bacteria for humans

- Bacillus anthracis (causes anthrax) (common in some parts of the world, not Australia)

- Bacillus cereus (food poisoning)

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Listeria (Regular shape and staining)

Listeria monocytogenes (listerosis)

- Severe disseminated infection in immune compromised people and in pregnancy - transmitted to foetus

- Usually acquired from contaminated foods (esp. cold meats, soft cheeses)

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NEED TO KNOW ALL THE NAMES OF THE SUBCATEGORIES OF EACH MAJOR CATEGORY!!

Corynebacterium (non-acid fast of irregular shape and staining of non-endospore formers)

- Normal flora of the skin - rare infections, except Corynebacterium diphtheriae - recent resurgence of diphtheria

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Diphtheria

- toxin mediated

- membrane on throat and bull-neck

- Vaccine preventable (toxoid vaccine)

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Myobacterium (acid-fast of irregular shape and staining of non-endospore formers)

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- tuberculosis

Actinomyces and Nocardia

- environmental organisms (soil) - uncommon human infections

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Bacillus Anthracis (of Bacillus (aerobic) which are endospore formers))

- causes anthrax

- Spores inhaled or ingestedor contaminate a wound

- Rapidly progressive, causesskin sores, vomiting, shock

- Bioterrorism agent

Clostridium perfringens (gasgangrene)

Clostridium difficile

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Clostridioides (Clostridium) difficile

- In faeces of most neonates and up to 30% of hospital patients

- we used to call it clostridium difficile but now we say clostridiodes

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SPORES WIDESPREAD IN ENVIRONMENT (LINK IN WA WITH PIG FARMING)

- spread on hands of staff, fomites

- spores difficult to eradicate

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TOXIN PRODUCING STRAINS CAUSE ANTIBIOTIC ASSOCIATED DIARRHOEA

- during of after antibiotic treatment

- mild to severe, intractible diarrhoea

- most severe: pseudomembranous colitis

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DISEASE IS A CONSEQUENCE OF DISRUPTION OF THE GUT MICROBIOME

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Pathogenesis of Clostridioides difficle infection

ASYMPTOMATIC COLONISATION

factors controlling C. difficile

- Colonisation resistance

- Bacteriocin secretion

- Bile acids composition

- Increased IgA levels

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EXPLANATION:

- if you get exposed to lots of C. difficile spores, from Health Care Facility (HCF), Food or PPI (proton pump inhibitors whcih basically reduce acid production in stomachs)

- the key thing is disrupting the normal microbiome that allows its growth

- antibiotics can wipe out bacteria in the colon which can give space for C. difficile to grow

- thats the reason its also in babies becasue they dont have a proper microbiome in gut

Treatment of Clostridioides difficile infection

- Antibiotics (metronidazole, vancomyocin)

- if refractory or severe, consider faecal transplant

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Definitions related to the human microbiome

- Microbiome: microbial community that occupies a well-defined habitat

Dysbiosis: An imbalance in the microbial community associated with disease - may be due to:

- Overgrowth of members of the commensal microbiota, e.g enterobacteriaceae, in inflammatory bowel disease

- Loss of commensals (e.g antibiotic therapy) - often accompanied by pathogen overgrowth, e.g Clostridioides difficile associated colitis

- Loss of diversity - documented in association with inflammatory bowel disease, HIV and type 1 diabetes mellitus

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Factors determining microbial community composition

ENVIRONMENTAL PARAMETERS:

- e.g oxygen tension, pH, temperature, energy sources

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INTERACTIONS BETWEEN MICROBES

Competition and Collaboration between microbes

- Positive example: cross feeding (one helps another)

- negative example (competing bacteria): bacteria produce antibiotics (bacteriocins) that inhibit the growth of competing bacteria

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RAPID EVOLUTION

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STOCHASTIC (UNPREDICTABLE) FORCES:

- e,g dispersal

How do we measure the microbiota and its function

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DNA:

- Gene Amplicon and Shotgun Metagenomics

RNA:

- Metatranscriptomics

PROTEIN:

- Metaproteomics

METABOLITE:

- Metabolomics

Composition of the gut microbiome

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- STOMACH

- DUODENUM

- JEJUNUM AND ILEUM

- COLON

Factors influencing the gut microbiome

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- should know all of these roughly

The role of the gut microbiome in health and disease

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- should know all of these roughly

A classic experiment: Obesity and the gut Microbiota

- Higher firmicutes to bacteriodetes ratio in obese

- Higher bacteriodetes to firmicutes ratio in lean

- Obese people who lost weight over a year: bacteriodetes level restored

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The gut microbiota and metabolic health

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DIET LOW IN ANIMAL FAT AND PROTEIN BUT HIGH IN PLANT FIBRES:

- microbiota related to metabolic health

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DIET HIGH IN ANIMAL FAT AND PROTEIN BUT LOW IN PLANT FIBRES:

- abberant microbiota related to metabolic diseases

Microbiome-directed interventions

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Myobacterium tuberculosis

- Tuberculosis (TB) is a global problem (30% world population infected, 1.4 million deaths p.a.

- disease of the lung, but can involve any organ in the body

- Poverty and crowding increase risk of TB

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Natural history of tuberculosis

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- a proportion of individuals are unable to control initial immune bacteria but they are able to control its growth sufficiently that they dont develop active TB

- they develop latent TB where there are live TB bacteria in the lungs and possibly other sites of the body but are coontained by the immune system

Acquisition of infection

- no animal or environmental reservoir

- direct human-to-human transmission

- Aerosol spread (vs. droplet spread)

- Very low infectious dose (1-10 bacteria)

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Adhesion, Invasion and Evasion

- Small droplet nuclei enter terminal airspaces

- Phagocytosed by alveolar macrophages

- Spread throughout body

- Survive within macrophages

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Myobacterium tuberculosis causes cavitation in the lung and in other organs

- Pathogenicity largely due to host inflammatory reaction tot he bacterium which causes tissue destruction

- No classic toxins

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TB treatment

- Need therapy with multiple drugs (to prevent emergence of resistant strains)

- Minimum treatment duration is 4-6 months for drug sensitive TB (slow-growing bacterium which develops tolerance to drugs (not all bacteria are killed by drug exposure))

Multi-drug therapy is needed for TB

- antibiotic resistance arises in TB as a consequence of chance spotaneous mutations in the chromosome

- antibiotics dont cause mutations to occur, they select for pre-existing resistant mutants

- TB doesnt actually do horizontal gene transfer (doesnt get new genes from other bacteria)

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- MDR is multidrug resistant (chance is very low)

- black dot shows multi drug resistance because you multiply the chance that its resistant to both common antibiotics

Chance of having Multi drug reistance TB strain

1 in 10 to the 14

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- diagram shows that there are basically 0 black bacteria

A person whos got TB bacteria that has been administered antibiotics

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- red dots are sensitive bacteria

- blue dots are resistant to iIsoniazid

- green dots are rifampicin resistant

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- so if we treat this patient with these antibiotics essentially none of the bacteria are going to survive

Tb patient just treated with INH

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- more common, so they will survive and grow

- therefore these resistant strains grow, giving rise to some that are also resistant to MDR (mutliple drugs)

Now treated with INH and Rifampicin

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- now you kill off all the blue ones, the black ones grow and duplicate

- now all of them are multi drug resistant

- this can be transmitted to another person