Antibiotic resistance:the end of modern medicine?

Associate Professor Siouxsie Wiles

Bioluminescent Superbugs Lab

@SiouxsieW

http://www.compoundchem.com/wp-content/uploads/2014/09/A-Guide-to-Different-Classes-of-Antibiotics-Aug-15.png

@SiouxsieW

http://www.biomedcentral.com/content/figures/1741-7007-8-123-1-l.jpgAntibiotic targets and mechanisms of resistance. Wright BMC Biology 2010 8:123 doi:10.1186/1741-7007-8-123

Broad vs narrow spectrum

Bactericidal vs bacteriostatic

@SiouxsieW

https://vimeo.com/180908160

@baym

@SiouxsieW

https://vimeo.com/180908160

https://vimeo.com/180908160

@baym

@SiouxsieW

https://vimeo.com/180908160

http://www.biomedcentral.com/content/figures/1741-7007-8-123-1-l.jpgAntibiotic targets and mechanisms of resistance. Wright BMC Biology 2010 8:123 doi:10.1186/1741-7007-8-123

@SiouxsieW

Taking up genetic material from their

environment

Transformation

Image credit: http://cnx.org/contents/GFy_h8cu@10.53:rZudN6XP@2/Introductionhttps://commons.wikimedia.org/w/index.php?curid=49931304

@SiouxsieW

Receiving genetic material after infection

with a virus

Transduction

Image credit: http://cnx.org/contents/GFy_h8cu@10.53:rZudN6XP@2/Introductionhttps://commons.wikimedia.org/w/index.php?curid=49931304

@SiouxsieW

Transfer of genetic material between

bacterial cells of same or different species

by direct cell-to-cell contact

Conjugation

Image credit: http://cnx.org/contents/GFy_h8cu@10.53:rZudN6XP@2/Introductionhttps://commons.wikimedia.org/w/index.php?curid=49931304

@SiouxsieW

Myth 3

It’s us that become

resistant to antibiotics

Image credit: http://www.mightyearth.org/wp-content/uploads/2016/10/CHANGING-MARKET-SUPERBUGS-IN-THE-SUPPLY-CHAIN-GUARD-FONT-FIN-PRINT.pdf

@SiouxsieW

https://www.flickr.com/photos/diethylstilbestrol/24474659711

“Discovery void”

@SiouxsieW

“the end of modern medicine as we know it”

Margaret Chan, former Director General

World Health Organization

@SiouxsieW

@SiouxsieW

@SiouxsieW

WHO Priority Pathogens

http://media.infectiousdiseaseadvisor.com/images/2017/03/02/globalpathogensprioritylist_1170810.jpg

@SiouxsieW

@SiouxsieW

@SiouxsieW

http://www.newshub.co.nz/home/health/2018/02/superbug-infects-national-burns-centre-patients.html

@SiouxsieW

Patient number

Species ResistanceLikely place of

acquisition

35

K. pneumoniae NDM-1

Tahitian hospital

P. aeruginosa NDM-1

37

P. stuartii NDM-1

Middlemore Hospital

K. pneumoniae NDM-1

K. oxytoca NDM-1

E. coli NDM-1

E. cloacae complex

NDM-1

@SiouxsieW

@SiouxsieW

https://surv.esr.cri.nz/PDF_surveillance/Antimicrobial/ACE/2018Carbap.pdf

@SiouxsieW

Clinical

Subclinical

Increase in transmission - colonisation

Detection of transmission & infection

@SiouxsieW

Private surgical hospital

Acute care hospital 2 ICU

Long term care facility B

Long term care facility A

Acute care hospital 1 Gen Med ward

Long term care facility A

Patient 1 March 2019

Overseas travel

Patient X May 2019 Patient Y July 2019

Long term care facility A

??

Blue arrows represent potential for further spread within the particular facility at each point

@SiouxsieW

@SiouxsieW

http://bwb.co.nz/books/antibiotic-resistance

@SiouxsieW

http://bwb.co.nz/books/antibiotic-resistance

@SiouxsieW

Bioluminescence

lux

operon

C D A B E

R T S

RT S

-

Fatty Acid

(RCOOH)

Aldehyde

(RHO)

? ?

? ?

Luciferase

FMNH FMN

NAD(P) NAD(P)HH+

Flavin

oxidoreductase

Light

(490nm)

O2 H

2O

lux

operon

C D A B E

R T S

RT S

-

Fatty Acid

(RCOOH)

Aldehyde

(RHO)

? ?

? ?

Luciferase

FMNH2

FMN

NAD(P)H+

Flavin

oxidoreductase

Light

(490nm)

O2 H

2O

lux

operon

C D A B E

R T S

RT S

RT S

Fatty acid reductase complex-

Fatty Acid

(RCOOH)

Aldehyde

(RHO)

? ?

Luciferase

FMNH FMN

NAD(P)H+

Flavin

oxidoreductase

Light

(490nm)

O2 H

2O

@SiouxsieW

Answer in seconds/minutes rather than days/weeks/months

Bacterial numbers

Lig

ht

levels

Dead or alive?

Counting live bacteria with light

@SiouxsieW

Image credit: Manaaki Whenua

@SiouxsieW

*Gross misrepresentation of the fungi in the ICMP…

*Hopefully not just penicillin again and again…

Brent CoppBevan Weir

Screening using light

@SiouxsieW

@SiouxsieW @SiouxsieW

Glowing chromatography!

@SiouxsieW

B

>800 tested

>500 active

>50 compounds

6 novel compounds

@SiouxsieW

Team fungi!

BenedictUy

DanielMulholland

Cleo Hall Strom

ChrisWille

DamienTan

SoerenGeese

Dr MelissaCadelis

YiweiDiao

AlexGrey

Sharavan de Pas

www.givingtoauckland.org.nz/fungi

@SiouxsieW