wiles illuminating new medicines rsnz 2015

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Siouxsie Wiles PhD

Nuria AndreuBrian RobertsonPaul ElkingtonTaryn FletcherNitya KrishnanShiranee SriskandanFaraz Alam

Andrea ZelmerUlrich SchaibleGreg BancroftSimon SwiftBrent CoppBill DennyBrian PalmerPhil CrosierDavid JenkinsJohn FraserKate HannahRichard EastherShaun HendyJim Metson

Jimmy DaltonBenedict UyHannah ReadZakieh Vahdati

Bevan WeirPeter Buchanan

Part I

Superbugs(AKA the microbial apocalypse)

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3

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the end of modern medicine as we know itMargaret Chan, Director GeneralWorld Health Organisation

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Part II

Living Light

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Angels Glow

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Part III

Illuminating new medicines

lux

operon

C

D

A

B

E

R

T

S

R

T

S

-

Fatty Acid

(RCOOH)

Aldehyde

(RHO)

?

?

?

?

Luciferase

FMNH

FMN

NAD(P)

NAD(P)H

H

+

Flavin

oxidoreductase

Light

(490nm)

O

2

H

2

O

lux

operon

C

D

A

B

E

R

T

S

R

T

S

-

Fatty Acid

(RCOOH)

Aldehyde

(RHO)

?

?

?

?

Luciferase

FMNH

2

FMN

NAD(P)

H

+

Flavin

oxidoreductase

Light

(490nm)

O

2

H

2

O

lux

operon

C

D

A

B

E

R

T

S

R

T

S

R

T

S

Fatty acid reductase complex-

Fatty Acid

(RCOOH)

Aldehyde

(RHO)

?

?

Luciferase

FMNH

FMN

NAD(P)

H

+

Flavin

oxidoreductase

Light

(490nm)

O

2

H

2

O

Bioluminescence:a simple chemical reaction

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12

Measuring bacteria with lightBacterial numbersLight levels

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14

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15

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Where are the bacteria?

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Day 1(10 min exp)

Day 3(5 min exp)

Day 6(1 min exp)

Day 8(1 min exp)

Day 10(1 min exp)

Day 14(1 min exp)103106103

Photons sec-1 cm -2 sr-1Watching bacteria in real timeWiles et al (2006). Infection and Immunity 74:5391-5396.

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10101081061021040510152025Time (days)Number of bacteria(colony forming units per gram tissue)

=Reducing animal useWiles et al (2004). Cellular Microbiology 6:963-972.

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=

Dennis et al (2008). Infection and Immunity. 76:4978-4988Reducing animal useTime (days)

Bioluminescence

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Part IV

Tuberculosis(AKA the Captain of Death)

Mycobacterium tuberculosis

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TB in New Zealand626 cases of TB reported in 2011

308 = infectious

318 = latent infection

54.2% in the Auckland region

Recent NZ Herald article placed the costs of treating multi-drug resistant TB at NZ$10,000 per month

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Andreu N, et al (2013). J Antimicrob Chemother. 68(9):2118-27.

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Fish-fanciers finger!

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Zebrafish for TB research

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Zebrafish for TB research

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Light levelsTime (days)A*B*CD*E*0303030303030303

UntreatedF*Rif*No activity in vitroZebrafish for TB research

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Part V

Want to help?

NZ Fungi as a source of new antibiotics?

Image credit: Landcare Research

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www.givingtoauckland.org.nz/fungi

Biolumination II

www.redbubble.com/people/siouxsiewShop with us!

[email protected]/user/Skeptimoo

www.sciblogs.co.nz/infectious-thoughts/

www.superbugslab.org

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