Bacteria Outline. 1. Overview. 2. Structural & Functional Features. 3. Taxonomy. 4. Communities

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1 Bacteria Outline 1. Overview 2. Structural & Functional Features 3. Taxonomy 4. Communities

2 Bacteria - Taxonomy PHYLUM CLASS ORDER FAMILY GENUS SPECIES SUB-SPECIES & STRAINS

3 Bacteria - Phyla Firmicutes Bacteroidetes 90% Proteobacteria Actinobacteria Tenericutes Verrucomicrobia Fusobacteria Cyanobacteria etc.

4 Do we really need to learn taxonomy? Yes. (if you want to interpret functional labs and understand the microbiome in depth)

5 Taxonomy + Function Important for Interpreting functional microbiome test results (stool tests, organic acid tests, etc.) Understanding probiotics and interaction with microbiome Understanding importance / relevance of scientific and clinical microbiome research Be patient! Mastering technical terminology takes time and familiarity.

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8 1. Lactobacillus acidophilus 2. Bifidobacterium bifidum PHYLUM CLASS ORDER FAMILY GENUS SPECIES STRAIN Firmicutes Bacilli Lactobacillales Lactobacillaceae Lactobacillus L. acidophilus DDS-1 Actinobacteria Actinobacteria Bifidobacteriales Bifidobacteriaceae Bifidobacterium B. bifidum ATCC 29521

9 Firmicutes Mostly gram-positive ( strong skin ) Tend to be associated closely with intestinal mucosa (vs. lumenal) Mostly coccus and bacillus forms Many can produce endospores Common groups: Lactobacillus (commensal and probiotic) Bacillus (commensal and probiotic) Clostridia (commensal)

10 Gram-negative & anaerobic Tend to be located lumenally (vs. mucosal) Rod-shaped Do not form endospores Common groups: Bacteroides Prevotella Bacteroidetes

11 Gram-negative Proteobacteria Facultative & obligate anaerobes Very diverse forms ( protean = capable of assuming many forms) Includes a variety of well-known pathogens / pathobionts Escherichia coli, Salmonella, Helicobacter pylori, Yersinia pestis (plague)

12 Actinobacteria Gram-positive Long rods & filaments Example: Bifidobacteria Verrucomicrobia Other Phyla Verruca = wart Anaerobic, gram-negative Example: Akkermansia muciniphila

13 A few notable groups and species (commensals, pathobionts, and pathogens)

14 Firmicutes > Clostridia Clostridia Abundant (10-40% of total gut bacteria) and complex group Very important group; some perform many beneficial functions Strictly anaerobic, gram-positive Colonizes near the epithelial barrier in the colon

15 Clostridia Major butyrate producers (feed colon epithelial cells) Also produce secondary bile acids from primary bile acids Form endospores Includes some pathogens: C. difficile, C. tetani, C. botulinum, etc.

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19 Clostridia Examples COMMENSALS Faecalibacterium prausnitzii Roseburia intestinalis Eubacterium rectale Coprococcus eutactus Clostridium scindens Butyrivibrio crossotus PATHOGENS Clostridium difficile (diarrhea, severe colitis) Clostridium tetani (tetanus) Clostridium botulinum (botulism, botox) Clostridium perfringens (food poisoning, gangrene)

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22 Akkermansia Muciniphila Phylum: Verrucomicrobia Relatively abundant: up to 3.0% of gut bacterial population on average Strictly anaerobic, gram-negative Colonizes the mucus layer; produces propionate and acetate from mucus SCFAs modulate gene expression via epigenetics Improves epithelial barrier function

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24 Pathobionts & Pathogens INTERNAL (Long-term) Commensals (Symbionts) Dysbiosis & Pathobionts EXTERNAL (Transient) Beneficial Microbes Pathogens & Parasites

25 Bacteroidetes Bacteroides fragilis Proteobacteria Pathobiont Examples Helicobacter pylori: Can cause ulcers and stomach cancer but may reduce esophageal cancer risk Bilophila wadsworthia: normal commensal but may contribute to colitis with high-fat diet Klebsiella: normal commensal but can cause infections (sometimes serious)

26 Bacteroides fragilis Obligate anaerobe, gram-negative Polysaccharide A: stimulates anti-inflammatory response (induces Treg cells) BUT, it can be a pathobiont Can produce a capsule (virulence factor) Common opportunistic pathogen in internal abdominal infections (leaky gut) Underscores importance of barrier integrity for both commensals and pathogens

27 Proteobacteria Salmonella enterica (typhimurium) Escherichia coli (pathogenic strains) Vibrio cholerae Pathogenic Bacteria Campylobacter jejuni Klebsiella pneumoniae Firmicutes > Bacilli > Lactobaciallales Enterococcus faecalis Enterococcus faecium

28 Taxonomy: Take-Homes Taxonomy important for working with microbiome Commensals: some groups and species play a special positive role Immune function, intestinal barrier, motility, many others Keeping pathobionts and pathogens in check Pathobionts & pathogens Can cause disease Depends on context, including the health of the individual, the overall health of the microbiome, and environmental factors

29 Bacteria Outline 1. Overview 2. Structural & Functional Features 3. Taxonomy 4. Communities

30 Adaptibility & Resilience Flexibility in using different substrates (depending on genes within each bacteria) Ability to tolerate variable physiological factors (oxygen, ph, bile, etc.) Rapid evolution of DNA Horizontal gene transfer (via plasmids) Replication rate, formation of endospores Community interactions, biofilms

31 Microbiome Communities Complex ecological communities of microbes Composition depends on local factors (physiological conditions, available substrates, other microbes, etc.) Highly interdependent, complex functional relationships (with each other & with us) Cooperate and compete Relatively stable & resilient

32 Physiological Factors Location Digestive tract region & microenvironment / niche Mucus layer vs. lumen Available substrates ph Oxygen Transit time / flow rate Barriers & immune factors Attachment sites Others: Redox status, bile salts, etc.

33 Substrates (Nutrients) Sources & types (diet, secretions, microbe metabolites) Availability Competition with other microbes Digestion / absorption by GI tract Concentration, flow rate, etc. Position in community food chain

34 Cross-Feeding & Competition A Resistant starch Butyrate SPECIES 2 SPECIES 1 C B Acetate SPECIES 3 SPECIES 4

35 Direct Competition Substrates (nutrients / metabolites) Space / attachment sites (mucus / epithelial later) Antimicrobial factors: organic acids, bacteriocins, lactocillin, etc. Indirect Suppress immune response to themselves Enhance immune response to competitors Others, including possibly affecting eating behavior

36 Cross-feeding / food web (mutualism) Metabolites produced by one species can be used as a substrate for another Coordination via quorum sensing Molecules used to coordinate activities Depends on density Sharing DNA e.g. - antibiotic resistance genes Biofilms Cooperation

37 Biofilms Bacteria + EPS (extracellular polymeric substance polysaccharides, proteins & nucleic acids) Normal part of many communities, but can contribute to pathogenicity (resistance to treatments) More stable, protected microenvironment Enables greater synergy & cooperation within community Contains extracellular enzymes external shared digestion

38 Colonization Resistance Capacity of microbiome communities to resist new colonization by pathogens and other transients (e.g., probiotics, foodborne microbes) Key to preventing GI infections: First line of defense Main factors contributing: Lack of niches (competition - space, available substrates) Hostile environment (ph, antimicrobial factors, immune factors) Biofilms Coordination (quorum sensing)

39 Stability & Resilience Above factors contribute to stability & resilience Stability: resistance to change, ability to maintain homeostasis Resilience: capacity to return to homeostasis after disturbance Diverse ecosystems are generally more stable & resilient Microbiome stability, resilience, & functional capacity contribute to human health & resilience Less prone to disruption of our homeostasis & health Contributes to tolerance of a wider range of foods and conditions Makes it challenging to change the microbiome BUT less diverse (less stable) microbiomes may be easier to change

40 Bacteria Outline 1. Overview 2. Structural & Functional Features 3. Taxonomy 4. Communities

41 Module 1 Overview 1. Microbiome overview: getting a sense of the microbiome, research, what we know 2. Bacteria: features, functions, communities & taxonomy 3. Other microbes: archaea, fungi, viruses, parasites (protozoa & helminths)

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