Microbial consortia are difficult to study All associations are different; Many specific mechanisms (antibiotics, physical barriers etc); No reliable “observables”;

Microbial consortia are difficult to study

• All associations are different;• Many specific mechanisms (antibiotics,

physical barriers etc);• No reliable “observables”;

• Generic (simplified) models:

1) synthetic communities (wet lab)

2) agent-based models (in silico)

Observed growth patterns

No (very slow) growth Swarming (fast, diffusion limited growth)

Constrained growth

Lab experiment

Sensing

Solitary / Planktonicstate (low signal production)

Activated state (production of secreted factors, increased signal production)

Increased metabolism and movement

Swarming, spontaneous community formation

Biological model: Quorum sensing

QUORUM SENSINGTheoretical model

Simplified example

Signal

Signal

Protease

Protease

aa

aa

Cell 1

Cell 2

Food

“Physicochemical” mechanism: production, diffusion, decay

Theoretical model

Regulatory model

[R-S]

Signal S

Signal synthase I Sensor R

Metabolism

Movement

1) Autoinduction, possitive feedback loop

S2) Equilibrium of internal and external signal levels

3) Can be studied with knockout mutants

Theoretical model

Regulatory model: communication and cooperation

[R-S]

Signal S

Signal synthase I Sensor R

Metabolism

Movement

Signal = communication

Sensing = cooperation

Non-communicating mutant

Non-communicating mutant

Theoretical model

Competition of strains: Cooperation or collapse

WT + SN

24 h

WT + SB

0

20

40

60

80

100

120

0 10000 20000 30000 40000 50000

Time

Rel

ativ

e sp

eed

of

po

pu

lati

on

(%

of

WT

ste

ady

stat

e)

Transient phase Steady phase

WT

WT+SN

WT+SB(QS collapse) SN or SB alone

(no movement)

“No swarming”

(NS)

“Swarming” “Collapse”

(C)

Phenotypes:

B

P. aeruginosaB. cepacia

0

20

40

60

80

100

center

popu

lati

on c

ompo

siti

on (

%)

0

20

40

60

80

100

border

popu

lati

on c

ompo

siti

on (

%)

P.aeruginosa + B. cepacia

A BC

1

WT+BC

2 97:3

Cooperation combines the skills of participants

Divided plate experiment: Center: Rim:

PA: + -

BC: - +

Collapse of a dendritic community

Ádám Kerényi

Blue: WT co-operators

Red: non-cooperating cheats

Computatonal model

B) 16 hours after SB injectionA) Before SB injection

= places of SB injection

C) Escaping dendrite magnified

Collapse is local: it protects against bad mutations....

Communication is not global....Iris Bertani

Lab experiment

Globally communicating community

(e.g. well-mixed, liquid media)

Locally communicating microcommunities

(e.g. swarming, growth on surfaces)

Local collapse, local communication

vulnerable stable

Dóra Bihary

Polymicrobial communities are less efficient but more versatile than (some) monocultures…

Summary

• Microbial communities were modeled with engineered bacteria and computer models.

• Non-communicating mutants can be part of the community, non-cooperating mutants cause (local) collapse.

• Microbial communities are stable because:– Cooperation combines the skills of participants.– Deleterious mutants are eliminated by local collapse

• Stability is a general consequence of local communication, it acts in absence of specific mechanisms… Polymicrobial communities are less efficient but more versatile than (some) monocultural communities…