Why do we work on it?Models to understand biology of sociality

To develop new medicines to treat devastatingbacterial infections

Understanding bacteria

Sociomicrobiology The “new” science of

Tools for synthetic biology

Sociomicrobiology We work on

Quorum Sensing

Biofilm biology Territoriality and self identity

Quorum Sensing: Bacterial Cell-to-Cell Signaling •Cell-cell signaling used to control specific genes. Allows coordination of group activities.

•The system that is most-well studied-acyl-HSLquorum sensing in proteobacteria. Over 200 species. Signals are dedicated. Made by LuxI familymembers. LuxR family of receptors. They regulatedifferent things in different bacterial species.

Acyl-HSL SignalingThe Vibrio fischeri Paradigm

The Mechanism of Quorum Sensing in Vibrio fischeri

The V. fischeri acyl-HSL signal

LuxI-type synthases produce a variety

of acyl-HSL signals

Other Bacteria Do ItQuorum sensing and control of public goods

•Light production in V. fischeri-no individual makes enough for biological detection, but we can see the collective activity of the group.

•Exoenzymes

•Toxics•Aggregation factors- “The first step in the origin of animal eusociality is the formation of groups within a freely mixing population” (Nowak, Tarnita and Wilson, Nature, August 2010).

Pseudomonas aeruginosa-an opportunistic pathogensenses cell density through quorum sensing

Low bacterial density,Low [QS signal],

Little activation of QS-controlledvirulence and biofilm genes

High bacterial density,High [QS signal],

Activation of >300 genes

P. aeruginosa Communicate via Two Quorum-Sensing Signals

C4-HSL

C12-HSL

RhlR-RhlIP. aeruginosa Acyl-HSL Signals

C4-HSL

C12-HSL

LasR-LasI

LasR-LasI regulates RhlR-RhlI. LasR-I is atop the quorumsensing cascade.

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RhlRI QscR

LasRI RpoS

MvfR

Vfr

GacA

RsaL

PA1760

PQS

ppGpp

ANR VqsR

QS regulon

RsmZ

RsmA ppGpp

RelA

ppGpp

The Integrated P. aeruginosa AHSL SystemsA Gratuitous Network Slide

Diverse Signals from Diverse Bacterial Species

- A structured community of bacterial cells enclosed in a self-produced polymeric matrix.

-Biofilms are a protective mode of growth that allows survival in hostile environments.-Bacteria in biofilms are inherently resistant to killing.

What is a Biofilm?

confocal microscope

influent

biofilm

effluent

polycarbonate base

CSLM to View Cells or Reporters in Flow Cell Biofilms

glass coverslip

Iron replete

Iron-A signal for biofilm development

Low iron

Iron as a Cue for Biofilm Development•A host iron chelator can block biofilm formation.•Iron is a signal in biofilm development-on glass.•Mutant P. aeruginosa that cannot take up iron form flat biofilms at high external iron levels.•We have identified several iron receptors-iron citrate, ornibactin, anguibactin, ferioxamine (two!).•Iron is functioning as a signal in the cytoplasm.

DFO-GaCapitalizing on basic information

We can make it and it is a tightly bound adduct

P. aeruginosa has two DFO-Fe uptake systems

Gallium is toxic to bacteria-Singh and co-workers JCI.

DFO-Ga Kills Biofilm Bacteria

Flow cells

Spinning disk reactors

DFO-Ga potentiates Gentamicin Therapy in Model Cornea Infections

DFO-Ga+gent

Systems and Synthetic Ecology

•Bacteria are cells, but they are also organisms.

•The way the organisms interact with each other has profound affects on their activities and drives their evolution.

•Systems and synthetic ecology has an enormous potential-new understanding, new medicines, new capabilities in manipulation.

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McFall-Ngai and Ruby