Relevance of microbes to health, industry and the environment 2100a course

1 Dr Carole CREUZENET, fall 2012

Lecture plan
• Microbes and life on earth: • Interactions with microbes: health aspects: - the good vs bad microbes - using microbes to produce vaccines • Microbes and agriculture / environment • Putting microorganisms to work - Metabolites of medical interest - Metabolites of technological interest - Production of foreign compounds
2

Figure 1.6a

Mammals Vascular plants Shelly invertebrates  20% O2

Humans

Origin of Earth
Present (4.6 bya)

1 bya O2 Algal diversity
y ro nl o bi al life for ms 3 2 bya bya

4 bya

Origin of cellular life

Anoxygenic phototrophic bacteria Anoxic Earth

M

ic

Modern eukaryotes

Earth is slowly oxygenated Origin of cyanobacteria
3

Figure 16.8 4 .

how much? • Adapt to O2 or survive underground or in anoxic pockets. • Most microbes are underground but current knowledge is from surface microbes.Where. Table 1.1 5 .

animals . Includes within animals and plants 6 . • Small fraction of surface microbes and microbes within plants and animals are key to higher order life.can make incredible chemical reactions. • Microbes constitute the bulk of the biomass on earth and are key reservoirs of essential nutrients for life.• Genetic and physiological diversity > plants.can live in places that would kill anything else .

the good vs bad microbes .Metabolites of medical interest .Metabolites of technological interest .Lecture plan • Microbes and life on earth: • Interactions with microbes: health aspects: .using microbes to produce vaccines • Microbes and agriculture / environment • Putting microorganisms to work .Production of foreign compounds 7 .

8 . .in humans: .nutritional value.digest and ferment cellulose at neutral pH.For digestive process: .critical to good health.Interactions with microbes: health aspects the good microbes . Rumen Grass Cellulose Glucose Microbial fermentation CO2  CH4 Fatty acids (Nutrition for animal) (Waste products) Figure 1.9d .human digestive microbes in the colon .in rumen of ruminant animals: .

1a Staphyloccous aureus 9 .beneficial or not Fig 1. vagina.skin.10 p9: oral flora Figure 18.Other sites occupied by bacteria: .Helicobacter pylori and others in stomach.digestive processes chemical . oral cavity.human stomach highly acidic .immuno-modulator and protective effects . nasal cavity. . .Interactions with microbes: health aspects the good microbes .

• Mapping of intestinal.via new sequencing technologies . skin… flora: .genome sequencing. IBD etc • All high impact studies. transcriptome . vaginal.relationship to disease.New ways of doing research on microbiota and health • Gnotobiotic mice models : – raised germ free – recolonized with known flora – relationship with immune system development and auto-inflammatory diseases IBD. 10 . See references. Crohns.

Science. Hooper et al. Nat Rev Neurosci. Diversity of the human intestinal microbial flora. Bäckhed et al. Science. 11 . . Gut feelings: the emerging biology of gut-brain communication. 2011. 2001 Commensal host-bacterial relationships in the gut. 2005. Interactions between the microbiota and the immune system Mayer. 2012.Hooper and Gordon. Eckburg et al. Science. 2005 Host-bacterial mutualism in the human intestine. Science.

Hygiene hypothesis Can It Be Bad to Be Too Clean?: The Hygiene Hypothesis http://www.scientificamerican. Barnes 2011 John Hopkins School of Medicine Lack of early childhood exposure to infectious agents. Since 1989… 12 . symbiotic microorganisms and parasites increases susceptibility to allergic and auto-immune diseases by suppressing natural development of the immune system.com/podcast Dr K.

Subtle but complex equilibrium (antibiotics  Clostridia invasion) Clostridium difficile outbreak over in 3 Ontario hospitals (CBC news.Niche occupation by normal microflora prevents colonization by pathogenic bacteria.Microbiology and Immunology department. . Lactobacilli mostly. July 2011) . 13 . The basis of an entire industry. teeth… new research area .Mixed cultures and surface growth: 3D structures (biofilms on rocks..Occupy the niche by “good bacteria”: Probiotics. .

000 population .Interactions microbes / humans: health aspects: the bad microbes Influenza and pneumonia Tuberculosis Gastroenteritis Heart disease Stroke Kidney disease Accidents Cancer Infant diseases Diphtheria Infectious disease Nonmicrobial disease 1900 (children/elderly) 0 100 200 14 Figure 1.8 (Part 1 of 2) Deaths per 100.

8 (Part 2 of 2) Heart disease Cancer Stroke Pulmonary disease Accidents Diabetes Alzheimer’s disease Influenza and pneumonia Kidney disease Septicemia Suicide 0 Today Children Developed countries Infectious disease Nonmicrobial disease 100 200 15 Deaths per 100.000 population .Figure 1.

coli blamed in European outbreak Canada to increase testing of European vegetables CBC news June 2011 16 . aerosols.Interactions microbes / humans: health aspects: the bad microbes • Problems in developing countries: microbial diseases are a major cause of death. water. person / person • Bacteria evolve fast: genetic exchange • Newly emerging diseases (bird or swine flu. 'Super-toxic' E. food. coli/Shigella hybrid in soy sprouts 2011). • Transmission: insects. new E.

 We can use microbes (virus.No prior exposure  no immunity .  Need for vaccines.  Need to study more complex populations..Threat of microbial bioterrorism. bacteria) to prepare vaccines to protect ourselves against microbes 17 .

Metabolites of medical interest .Lecture plan • Microbes and life on earth: • Interactions with microbes: health aspects: • Microbes and agriculture/environment: .the good vs bad microbes .Metabolites of technological interest .bioremediation • Putting microorganisms to work .Production of foreign compounds 18 .

• Ex: Other bacteria cycle sulfur compounds: oxidize toxic sulfur species (hydrogen sulfide H2S) into sulfate SO42which is an essential nutrient.9a N-cycle S-cycle 19 .Microbes / agriculture: good microbes • 1/ To grow crops: benefits from cycling of nutrients • Ex: legumes & nitrogen fixing bacteria: convert atmospheric N2 to NH3 used as food source by plants. No need for costly and polluting fertilizers. Figure 1.

dairy products (yoghurt. veggies (sauerkraut. cheese. • 3/ To clean up the environment: Bioremediation 20 . Baked goods and alcoholic beverages use yeast.• 2/ To transform crops in better foods: . some sausages. pickles). buttermilk).preparation of many food products rely on the fermentation activities of microbes .

add microbes to a polluted site. • 2 ways for bioremediation: . • Some bacteria can prey on others and destroy them. .Microbes and the environment: Bioremediation • Microbes can consume spilled oil. pesticides. or other toxic pollutants. 21 .add nutrients that stimulate the pre-existing microbes into degrading the pollutant. solvents.

 huge economic losses in the agricultural industry. • Microbial-based food spoilage during storage / commercialization Major economical losses. monitoring of pathogens and tracking 22 .Microbes / agriculture: bad microbes • Microbial disease of plants and animals  less growth yields. Canning. frozen-food and dried-food industries Food safety. lower value of crop.

Lecture plan • Microbes and life on earth: • Interactions with microbes: health aspects: .Metabolites of technological interest .Metabolites of medical interest .Production of foreign compounds 23 .using microbes to produce vaccines • Microbes and agriculture: good vs bad microbes • Putting microorganisms to work (commodities) .the good vs bad microbes .

24 .Putting microorganisms to work at the industrial scale to produce commodities • In industrial microbiology. microbes grown on large scale to produce bulk compounds of low commercial value (ex: antibiotics) • In biotechnology uses genetically engineered microbes to produce compounds of higher commercial value (ex: human proteins) • See bacterial genetics for molecular basis • Main microbes: fungi (yeasts and mold) and some prokaryotes (mostly of genus Streptomyces).

. animals. whey (dairy industry) corn steep liquor (corn wet-milling industry). vaccines) .000 liter fermentors with control systems. for humans. plants.High product yield (selection or genetic engineering).Not pathogenic (safety). .the microbes themselves (probiotics.the substances made (see table next) 25 .Grow easily in large scale cultures 500. Waste carbon. . What are the products of industrial microbiology? .• A few requirements for the microbe: . .Use cheap liquid growth medium.

Growth conditions. Ex ethanol. Produced by spore-forming microbes 26 .Table 15. • Secondary metabolites: formed in stationary phase. Over-produced as groups of related compounds.1 • Two types of metabolites: • Primary metabolites: formed in exponential phase. More complex and important metabolites Non essential for growth.

sugar.1a Alcohol.Figure 15. or cell number Primary metabolite Cells Food Secondary metabolite Food metabolite metabolite Cells Time Time 27 .

Metabolites of medical interest: antibiotics • Most important product of health industry • Human health and cattle industry. 28 . • Produced by a microbe to kill or inhibit growth of others. • Produced by fungi or by bacteria • About 15 years and ~ 1 billion from discovery to clinic • Very few new antibiotics discovered in the past 20 years despite increasing antimicrobial resistance. • Antibiotics are typical secondary metabolites.

broad spectrum. .Taylor final compound via composition of growth medium 29 . .Made using corn steep liquor (for nitrogen and growth factors) and whey as lactose source.Produced by fungi Penicillium and Aspergillus and certain prokaryotes. Ex ampicillin .beta-lactam antibiotics .Example: penicillins .

30 .Knowledge of metabolism to increase growth of microbe and yield of production. using sucrose as carbon source.Example: tetracyclins Chlortetracycline . .Produced by a Streptomyces. .30 genes to make it. .Made mostly from corn steep liquor.

produced using Corynebacterium glutamicum. .aspartic acid and phenylalanine: used to produce the artificial sweetener aspartame . Corynebacterium glutamicum. made by Gram positive bact.Other metabolites of medical interest: vitamins and amino acids . nutraceutical (nutrition supplement) and food industries. .monosodium glutamate MSG: flavour enhancer. Serve as cofactors. .Production of amino acids requires selection of mutants with deregulated control of amino acid synthesis.lysine. .Complex vitamins such as B12 and riboflavin can not be make chemically inexpensively.Used in pharmaceutical. 31 . essential for humans and domestic animals.

Enzymes with extreme optimal conditions : Ex: DNA 32 polymerase for PCR. lipids and starch. Produced by Bacillus.5 p 421.Exo-enzymes produced in high amounts and secreted outside the microbe to digest cellulose.Applications in food and health industries and in laundry and textile industries.Proteases.Metabolites with technological applications: enzymes . Degrade proteins. Used in laundry detergents. . . . Glucose converted by second enzyme into fructose (sweeter) used in food/beverage industry . proteins.Amylases and glucoamylases: to make glucose from starch. . Table 15.

resistant to alcohol. controlled taste ) • Possible bacterial secondary malolactic fermentation: Bitter malic acid  smooth lactic acid + extra flavors. 33 . • For wine: fermentation by yeasts first (wild or selected. Applications for alcoholic beverages and biofuels • Alcoholic beverages by fermentation of a grain. vegetable or fruit by yeasts or bacteria to yield ethanol and carbon dioxide.Metabolites of commercial interest: alcohols .

• For beer: brewing: production of alcoholic beverage from malted grains. • Use Saccharomyces yeast for fermentation of glucose 34 . • Malt: made from germinated seeds (barley mostly) • Contains natural enzymes that digest the starch from the grain and convert it to glucose.

– Ethanol can be produced by fermentation of glucose comprised in feedstock (sugar cane or starch) – Biodiesel can be produced from soybean. – Waste material versus feedstock 35 . – Petroleum: made by fermentation by green algae or engineered bacteria for ad hoc products.Biofuels – Methanogenic microbes produce methane (natural gas) by anaerobic degradation of organic matter.

• Mix with gasoline to reduces emissions of CO2 and NO2 upon burning.Ethanol • Obtain glucose from corn starch or other and ferment by Saccharomyces. High [ethanol]  modified engines. • Paradox: it takes 25% more energy to make 1 l of ethanol than there is energy in the ethanol itself • Called biofuel as it is made from fermentation of recently grown plants as opposed to fossil fuel. 36 . Ethanol extracted by distillation.

Metabolites of medical interest .the good vs bad microbes .Metabolites of technological interest .using microbes to produce vaccines • Microbes and agriculture: good vs bad microbes • Putting microorganisms to work (commodities) .Production of foreign compounds 37 .Lecture plan • Microbes and life on earth: • Interactions with microbes: health aspects: .

• Ex: somatotropin: human growth hormone.Making microbes produce foreign compounds: Expressing mammalian genes in bacteria • make bacteria express compounds that their genome does not code for  Genetic engineering • Difficult. • Also used in dairy industry to stimulate milk production via activity on prolactin receptor. only valuable products. Produced by bacteria. smaller scale. avoids immune reaction to insulin that was previously extracted from animals. 38 . Lack of hormone causes hereditary dwarfism. • Ex: insulin: First product of genetic engineering.

agriculture and environment and by their products. • Quote from Louis Pasteur. natural or engineered. founder of Microbiology: “the role of the infinitely small in nature is infinitely large”.Take home message .Microbes are essential for life and their activities can cause significant benefit or harm to humans via their effects on health. • Intrigued enough about microbes and what they can do? Enjoy 2100a !! 39 .

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