Exam 4 Microbio

Symbiosis

Association of one organism with another

Facultative interaction

Microbe has an alternative lifestyle

Obligatory interaction

Absolute requirement for another organism (some level of coevolution)

Consortium

A host with more than one associated symbiont

Consortium Time

Intermittent and cyclic or permanent

Mutualism

Both organisms benefit from the interaction, some degree of obligatory relationship

Cooperation

Both Organisms benefit but the relationship is not obligatory

Commensalism

Organism A benefits while organism B is unaffected
Unidirectional

Often Syntrophic

Syntrophy

Cross feeding,
One organism benefits from metabolic products of the other organism
Modification of environment where one benefits from another

Predation

A predator attacking and killing it’s prey
Predator obtains biochemical precursors and energy after the prey is dead

Parasitism

A parasite exploits it’s host for it’s own gain

Obtains biochemical precursors and energy while the prey is still alive

Always some co-existence

Successful parasites have evolved to co-exist

Amensalism

Organism A exerts a negative effect on organism B

Competition

Occurs when two organisms try to acquire or use the same resources

Competition out come A

One outcompetes the other for resources of a site

Competition outcome B

Both coexist at lower levels due to limited resources

Positive Interactions

Mutualism, Cooperation, Commensalism

Negative interactions

Predation (killing)
Parasitism (exploitation)

Amensalism

Competition

Mutualism Microorganism-insect relationship

Aphids (insect) and B. aphidicola (bacteria) have coevolved, B. aphidicola is an enosymbiote

B. aphidcola produces amino acids for aphids and cannot survive outside of aphids

Mutualistic Protozoan-termite relationship

Lignocellulose is broken down by Trichonympha sp. (a protist)

TRichonympha protist may further have its own symbiont nitrogen fixing bacteria, such as Elusimicrobium

Other examples of Mutualism

Nitrogen fixing bacteria and legumes

Mycorrhizae and plants

Cooperation example, Bacteria and nematode relationship

BActeria lives in nematode gut

Nematode eats insect larvae, bacteria release enzymes and toxins that kill larvae using T3SS

The bacteria releases antimicrobial compounds which prevent other microbes from consuming the cadaver

Nematode uses insect corpse as nutrient source to reproduce, and the bacteria colonizes juvenile nematodes before emergence

Commensalism and sharks

Sharks will kill prey and fish will feed on leftovers

Commensalism example Nitrification

Syntrophic
Nitrosomonas and Nitrobacter

Nitrosomonas converts NH3→NO2 for energy, Nitrobacter uses NO2→NO3 for energy

Commensalism and milk

Microbial succession during milk spoilage
Lactobacillus can be found in milk (gram positive, anaerobic) ferments lactose→lactic acid
Changes the environment of milk, allows us to consume as lactic acid prevents formation of pathogenic organism

Commensalism and biofilms

Need a surface
Organisms colonize the area and release adhesion factors, metabolic by products

Teeth have biofilms

Predation Vampiroccus

Uses an epibiotic mode of attacking prey
Goes into periplasmic space and secretes degradative enzymes into the cytoplasm
Lyses cell and gets contents from cytoplasm

Epibiotic

Attaches to the surface of prey, does not enter.

Bdellovibrio

Penetrates the cell wall, but grows outside the plasma membrane

Lyses cell membrane and consumes nutrient

Bdello Vibrio Specifics

SWims at rapid rate and bores a hole through cell wall, flagella is lost before it enters periplasmic length.
BDello vibrio grows 4 times in length, and host cell becomes rounded forming a bdelloplast
Elongated bdello vibrio splits in 4 smaller cells, the wall then lyses

Daptobacter

Penetrates prey and directly consumes cytoplasmic contents

Endosymbiont

Myxococcus

Wolf pack, cells use gliding motility to creep, overtake their prey, and release degradative enzymes

Facultative predator

Parasite example Mycobacterium leprae

Experienced genomic reduction

obligate intracellular parasite cannot grow outside of a cell, depends on host

Competitive exclusion principle

One organism dominates, other dies/low pop

Contact dependant growth inhibition

Cells need to be in close physical proximity to deliver compounds that inhibit growth of other organism

Mediated by T5SS and T6SS

Negative impact of one on another

Vibrio cholerae and Pseudomonas aeruginosa use T6SS to kill gut microbiota, as well as against host cells to cause disease.

Contact independent growth inhibition

Ammensalism, where organism secretes diffusible compounds to inhibit other organism

Colicin

Produced by E. coli, a bacteriocin

Toxin that kills other microbes

Cycles can occur, where some Produce, Become sensitive, become resistant

Ammensalism mechanism

Contact independent growth

Antibiotic production, compounds are diffusible

Streptomyces produce antibiotics

• Antibiotic production

• Bacteriocin production

Kirby Bauer

Lawn inoculation

Antibiotic disks, zone of inhibition

Human-Microbe interactions

Diverse environment with various specific niches and dynamic relationships, change across life

Microbiome

All of the genes found in one’s microbiota

Superorganisms

When gene-encoded metabolic processes of the host become integrated with those of the microbes

Human microbiome project what happened in 2007 and 2014

Started in 2007 by NIH

As of 2014:

• Whole metagenomic sequencing data of 800 healthy ppl obtained

• 16S sequence data from 5000 healthy ppl

Information gained may shed light on complex interactions

Metagenomic sequencing

What are the 5 phyla present in most people

Actinobacteriota, bacteroidota, firmicutes, fusobacteria, proteobacteria, and verrucomicobiota

Bifidobacteria

Found in breastfed babies, first bacteria to colonize the gut

Milk helps to select for nonpathogenic bacteria

Milk has specific polysaccharides that benefit specific bacteria

Levels decrease as you age

Environment determines the amount

C section impact on bifido bacteria

Decreases the amount of bacteria in babies

Bifidobacteria characteristics

gram positive

obligate anaerobe

fermentation, provides calories for us and other microbes in biome, lowers gut pH

can synthesize amino acids (prototrophic)

Probiotic

Bifidobacteria lowers gut pH

Commensalism, mutualism, and ammensalism

Germfree Animals

Studied to determine necessity/effect of microbes

• Compare normal to gnotobiotic mammals

• Introduce single microbes

Coupled with genomic studies for maximum benefit

What do we learn from gnotobiotic animals

Gut brain axis, digestion, metabolic processes, what and how they eat?

Gnotobiotic

Gnostos: known

Bios: life

Living organism reared in environment where every microbe is either known or absent

Skin microbiome

Largest organ

Lots of resident/transient microbes

Skin environment

Slightly acidic pH

high salt concentrations

low moisture

highly varied

Skin inhibitory substances

Lysozymes and antimicrobial peptides (AMPs) by macrophages and granulocytes

oleic acid by gram positive C. acnes to inhibit gram negatives

Cause of Acne?

Acne vulgaris caused by cutibacterium acnes, live in follicles and pores

sebum accumulation in puberty feeds cutibacterium acnes

opportunistic pathogen

Creams and antibiotics treat

Staphylococcus epidermidis

Supports keratinocyte growth and controls pathogen growth

Can grow on salt, halotolerant

Coagulase

Deoderants

Contain antibacterials

MRSA

Staph aureus also found on our skin, low levels

Staph. aureus

Eye microbiota

Small number of commensal bacteria found on conjunctiva (clear membrane) of the eye

Predominant bacteria is staph. epidermidis

Conjunctivitis, yellow pus

External ear microbiota

Similar to that of skin

Has fungi, C. auris

Mouth Microbiome

Dental plaque, dental caries, gingivitis, periodontal disease

• streptococcus parasanguinis, S. mutans and S. salivarius

Oral cavity colonized by microorganisms from surrounding environment

After teething phase, obligate anaerobes become dominant

Why do obligate anaerobes become dominant?

Anoxic nature of area between teeth and gingiva

Stomach microbiome

Very acidic, pH of 2-3

Very few microorganisms can survive

• Streptococcus, staphylococcus, Lactobacillus, Peptostreptococus spp. and Candida spp.

Some can survive if ingested with food

10 viable bacteria/mL of gastric fluid, transient

Maybe spores

H. pylori increases pH in the stomach and causes ulcers

Intestinal microbiome

Varies from section to section

Duodenum (SI)

Contains very few microorganisms, where acid initially enters from the gut

Jejunum (SI)

Enterococcus faecalis, lactobacilli, and C. albicans

Higher pH than Duodenum

Ileum (SI)

Flora similar to colon

pH becomes more alkaline

Anaerobic gram-negative and Enterobacteriaceae

Large intestine

Largest microbial population of body

Replaced rapidly because of their high reproductive rate

Most microbes are anaerobes

fermicutes and bacteriotes

ferment food we can’t digest, create vitamins, intermediates, beneficial to immune systems, metabolize dietary toxins, mature our immune system

Protect against enteric pathogens

Respond to diet

10^12 cells/stool

Nose and Nasopharynx

Close to the skin, large overlap

S. aureus and S. epidermidis

• predominant bacteria

• just outside the nostrils

Nasopharynx may contain low number of potential pathogens

• Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae

Oropharynx microbiome

Divvision of pharynx between soft palate and upper edge of epiglottis

• alpha hemolytic streptococci

• diphtheroids (gram positive)

• Gram-negative cocci

• anaerobes in tonsillar crypt

Lower respiratory tract

Consist of larynx trachea, bronchi and lungs

Previously believed to lack normal microbiota

Has transient bacteria

Microbes moved by

• continuous stream of mucous generated by ciliated epithelial cells

• phagocytic action of alveolar macrophages

• lysozyme in mucus

Genitourinary tract antimicrobial properties

Unfavorable for foreign microbes

• low pH of urine and vagina

• vagina has lactobacilli

• urea and other toxic metabolic end products in urine

• hypertonic nature of kidney medulla

Flushing with urine and mucus

Distance Barrier of male urethra

Usual flora:Kidneys ureter, and bladder

Normally microbe free

Kidney or UTI is bad and painful

Distal Urethra

Few microbe found

Female genital tract

Complex microbiota in state of flux due to menstrual cycle

acid tolerant lactobacilli predominate (pH 4.4-4.6), prevent pathogenic bacteria from surviving, prevents yeast infections

Functional core microbiome

Core microbiome is required for homeostasis

Rely on our gut microbiota

• vitamin K by E. coli

Research has focused attention from individual species to metabolome

• products these microorganisms secrete

Role of Fiber

Fiber is broken down by microbes→ferment monomers into short chain fatty acids

• butyrate: intestinal epithelial cells→CO₂, help with oxidation of glucose

• propionate: inhibits cholesterol synthesis, travels to the liver regulates weight, suppresses hunger, releases intestinal hormones

• acetate: absorbed by host cell, precursor for lipid in liver and fat cells, can be reabsorbed, causes weight gain

Gut Microbiome when overweight/obese

Higher concentration of Firmicutes relative to Bacteroidota

• increases production of acetate

• Increases intake and storage of lipids and fat in our cells

Increase in methanogens and archaeans, consume hydrogen gas and increase fermentation, IBS

Fecal Microbiota Transport

Transplants of healthy stool with healthy microbiome, can be taken in a pill to repopulate gut of unhealthy individuals

Immunity

Colonization resistance is based on competitive exclusion and ammensalism

Exogenous Antibiotics disrupt the gut microbial community

Gut microbes can release toxic peptides that target pathogens

• bacteriocins, microcins, colicins

Indirect mechanisms

Induction of Host Cell response:
SCFAs, peptidoglycan→antimicrobial peptides Enterococcus listeria

SCFAs Bile acid modifications→ host immune cell response, clostridioides difficile/ E. coli

Direct Mechanisms

Interaction between gut microbes:
Nutrient consumption→E. coli, Salmonella, C. diff

Bacteriocins,TypeVI secretion system dependent toxins→ Pseudomonas, Vibrio, Bacteroides

Gut-Brain Axis

Gut microbiota may affect CNS

Specific behavioral traits: inquisitiveness, sociability, anxiety, depression

Ways the microbiome can influence the CNS:

• microbiome effect on immune system

• Enteric nervous system, connected to CNS by vagus nerve

• Soluble microbial products (SCFAs) such as butyrate

Dysbiosis

Imbalance of the microbiota in the body

Dysbiosis Effects on cardiovascular disease

Diets high in red meat and high fat foods:

• high l-carnitine and phosphatidylcholine→accelerates atherosclerosis

diet low in fiber: low anti-inflammatory SCFA

Cancer and Dysbiosis

Microbes involved in 20% of malignancies

• Products alter the host cell cycle to favor proliferation

• prevent host cells from repairing damage

Many are driven by inflammatory state

bacteria can be involved in metastasis

Can cause issues in tight junctions of the intestine, lead to inflammation

Probiotics

Live organisms which, when administered in adequate amounts, confer a health benefit to the host

Probiotics are unregulated, claims not rigorously tested

Synbiotics are foods that contain both prebiotics and probiotics

Innate Immune system

Non-specific immune response

Natural

first line

resistance to any microbes

lacks memory

Adaptive immune response

Adaptive

resistance to a particular foreign agent

has memory

Pathogens need to overcome:

Surface barriers

Resistance by host

• nonspecific immune resistance

• specific immune response

Definition of Immune system

composed of widely distributed cells, tissues, and organs

recognizes foreign substances or microbes (antigen)

acts to neutralize or destroy them

Immunity definition

ability to resist a particular disease or infection

Physical Barriers

The first line of defense

1. Skin

2. Mucous Membranes

• Respiratory system

  • mucociliary escalator

• GI tract

  • Gut associated lymphoid tissue (GALT)

  • M Cells, detect foreign microbes

• genitourinary tract

  • flushing

Chemical Mediators

Antimicrobial peptides and proteins

• most ancient primary defense mechanism

• many are positively charged and amphipathic (hydrophillic and hydrophobic)

• examples: lysozyme, lactoferrin and granzyme

• lysozyme 1,4 bond of NAM NAG

Host cell

Innate immune system, in tears and saliva

LActoferrin

Secures iron, cofactors

Granzymes

Punch holes in membranes of certain microbes

Two major types of antimicrobial peptides

• cationic antimicrobial peptides CAMPs

• bacteriocins

Cationic Peptides

Produced by host cells, humans

Three classes of Cationic peptides?

First class: cathelicidins

Second class: alpha/beta defensins

Third Class: histatin

Cathlecidins

Secreted initially inactively

Activated upon a signal, broken down by proteolysis to activate

Broad-spectrum, produced by a variety of cells

Permeate cell wall and cause leakage

Alpha /Beta defensinsDefensins

REleased as a precursor protein, broad spectrum

Found in neutrophils, intestinal paneth cells, intestinal and respiratory epithelial cells

detection (paneth cells)