18: Microbial Symbioses

Microbial Relationships

Symbiosis = living together of 2 organisms

• Mutualistic = reciprocal benefit to both partners

• Commensalistic = benefits 1 organism, the other is neither harmed nor benefited

• Pathogenic = benefits 1 organism, the other is harmed

Human microbiome

• There are approximately 10^13 microbes in the human microbiome living in complex communities.

• There are approximately 10^13 of our own cells in our bodies

  – 1:1 ratio, not 10:1 as previously thought

• There are about 10x more bacterial genes in this population than human genes

Biofilms

Growth of complex, slime-encased communities (dynamic, interactive)

Planktonic growth: growth as suspension

Sessile growth: attached to surface

• can develop into biofilms

• attached polysaccharide matrix containing embedded bacteria

Biofilms form in stages:

• Planktonic cells attach.

• Sticky matrix forms.

Microbial mats: multilayered sheets with different organisms in each layer (e.g., hot springs, intertidal regions)

Biofilms

• Biofilms prevent harmful chemicals (e.g.,antibiotics) from penetrating, prevent protists from grazing, and prevent washing away of cells.

• Biofilms affect human health, water distribution systems, and fuel storage.

• Benefits to microbes:
  – ↑ nutrient concentration
  – ↑ resistance
  – ↑ communication & gene expression

  – movement to other locations.

Biofilm development

Pathogenic bacteria in biofilms are physiologically different

• ↓ sensitivity to antibiotics

• ↑ resistance to host defense mechanisms

Cell-Cell Communication

Quorum Sensing

• Communication using small organic molecules – allows cells to assess population density

• target level induces gene expression

  • mutualism, pathogenicity

How do bacteria sense others?

• Bacteria actively communicate with each other to coordinate gene expression as a population

• Quorum Sensing: the process of detecting the population size and changing group behavior once a large enough population is present

Quorum controlled behaviors

• Biofilm formation

• Motility

• Differentiation

• Competence

• Light production

• Toxin production

Signaling molecules

Gram Negatives:

• Autoinducers

  • Acyl homoserine lactones (AHLs)

Gram Positives:

• Oligopeptides

Signaling Molecules

Autoinducer-1: talk within a species

• AHL with specific R group

Autoinducer-2: talk between species

Autoinducter-3: talk between a pathogen and its host

Signaling molecules

Small

Membrane permeable in both directions

Passive diffusion

Quorum receptors

Cytoplasmic

DNA binding proteins or sensor kinases from two-component signaling systems

Cell-Cell Communication: Quorum Sensing

Low cell density v.s. High cell density

High cell density → AHL signal will act as an inducer and can create gene expression of Quorum proteins

Cell-Cell Communication: Quorum Sensing

Example: marine bioluminescent bacteria (Vibrio fischeri)

• autoinducer = AHL (AI-1)

• host-microbe interaction

  • microbe provides light

  • animal provides nutrients/habitat.

Differentiation controlled by AI-1

Myxococcus lifecycle

Signaling between species

Autoinducer-2

• one of few biomolecules to contain Boron

Produced by, and sensed by diverse bacterial taxa

• Receptor is a sensor kinase (HPK-RR), changes gene expression

• Some bacteria can only respond to but don’t produce AI-2

  • stealth!

Signaling between kingdoms

Autoinducer 3

• Produced and sensed by EHEC

  • coordinates transition from motile/avirulent to adherent/virulent

  • induces expression of type III secretion system

• Also sensed by human cells

  • activates inflammation

  • helps to clear infection

• The AI-3 receptor can also be activated by epinephrine and norepinephrine to induce virulence gene expression

Signaling between kingdoms

• The bacteria is listening to the host, and the host to the bacteria

  • bacteria: cause infection

  • host: resist infection

• QseC: the AI-3 receptor can also be bound and inhibited by cannabinoids (endocannabinoids and plant derived)

Gram positive signals

AIP: auto-inducing peptide

• made as pre-peptide

  • leader cleaved off during transport to make active only after export (why?)

• AIP sensed by a sensor kinase and gene expression regulated

Interfering with quorum sensing

Many quorum sensing behaviors are detrimental to humans

• biofilms

• virulence

Traditional antibiotics lead to selective pressure

Targeting quorum sensing, also termed quorum quenching, could lead to less antibiotic resistance

Probiotics and quorum quenching

AI-2 production:

• production of AI-2 by a probiotic strain can inhibit virulence gene production by a pathogen

Peptide produced by B. subtilis can bind to AIP receptor of S. aureus

• prevents sensing AIP levels

• prevents activation of virulence genes

Nutritional cooperation

Nitrogen fixing bacteria invade plant root cells

• plant provides sugars, protection and anaerobic environment

• microbe provides fixed nitrogen

Enteric Microbial Community of Animals:

Animals are colonized extensively by bacteria, archaea and fungi in their gastrointestinal tracts to aid in digestion of food:

• plant polymers especially

Carnivores and omnivores have mutualistic relationships with enteric microbes, but herbivores are totally dependent on microbial filtration

Microbes also produce beneficial compounds for the host

• vitamins

• short chain fatty acids

Different organization of animal digestion:

• The digestive tract is responsible for breaking down food and absorption of nutrients from the food

• All vertebrates have an acidic stomach and large and small intestines

Organization of animal digestion

• The acidic stomach is a barrier to survival for most microbial species

• The large and small intestine are responsible for nutrient absorption

• Microbes can be found throughout the digestive tract but are found at high density in specialized subsections

  • if before stomach=foregut fermentation

  • if after stomach=hindgut

Herbivory

Herbivory has evolved many times in mammals.

• As has association with microbes

Plant polymers are the most abundant carbon source for land animals

Vertebrates cannot digest, rely on microbes

• specialized anoxic compartments

  • rumen

  • cecum

  • colon

• extended time

Foregut vs Hindgut

• Foregut fermenters are more efficient at digesting plant material

  • horses vs cows

• Foregut fermenters get more protein from the microbes that pass with the food into the acid stomach

• Some hindgut fermenters (rabbits) will practice coprophagy to recover some lost microbes and lost proteins

Ruminants

The most abundant herbivory strategy for land animals

Specialized foregut fermentation organ

Microbes participate in the conversion of cellulose to glucose and the fermentation of the glucose to volatile fatty acids (VFAs)

VFAs directly enter bloodstream

• used as nutrients by other cells in body

Other fermentation products are gasses that are burped out by the animal

Agricultural ruminants contribute 14.5% of the greenhouse gasses annually

Termites

Termites have symbiosis with microbes capable of degrading plant polymers found in wood

Termites as hindgut fermenters

• Insects do not have the same acidic stomach and small and large intestine that vertebrates have

• But the termite has specialized fermentative organs in the hindgut that harbor specific microbes for digestion of wood to provide energy

Humans as hindgut fermenters

• As omnivores we are not obligate fermenters, but we derive energy and nutrition from the microbial communities in our small and large intestines

• Microbes throughout, but highest density and diversity in colon

Stomach is not sterile

Helicobacter pylori

• linked to gastric ulcer

Barry Marshall self experiment

• Nobel Prize in 2005

Produces CO2 as part of metabolism

• non-invasive breath test

Colon

• Majority of microbial numbers and diversity in humans

• Anaerobic

  • though facultative anaerobes are also present

• Outer mucus layer colonized, inner mucus layer protects cells

Products produced by human gut microbes

vitamins

• B12

• K

“essential” amino acids

volatile fatty acids

Butyrate

While several volatile fatty acids are produced by human enteric microbes, butyrate has been best linked to positive health outcomes

Local effects of butyrate:

• Increases integrity of the gut barrier

• Reduces oxygen content

  • less growth of pathogenic microbes

• Signals to local immune cells to suppress inflammation

Systemic effects of butyrate:

Butyrate enters the bloodstream

Can be used as an energy source

Also can reduce inflammation systemically

Butyrate and the gut-brain axis:

• Signals produced by the microbiota in the gut can be sensed by neurons and can cause wide scale changes in psychological and neurological disorders

• Butyrate is one signal
  • can also cross blood-brain barrier to act in CNS

• More supported by animal models than human trials

• Butyrate from the gut microbes enters the blood and can alter inflammation in other organs

• High levels of butyrate producing microbes in the gut can make the immune cells in the lung better able to clear bacterial and viral infection

  • also can limit damaging inflammation and production of scarring in the lungs after severe viral infection