01/23

Rustad et al, 200902/23

03/23

The birth of Antibiotics:

Pencillium notatum

04/23

• Pleuromutilin produced by Clitopilus sp(Pleurotus sp )

• Active against gram positive bacteria• Binds to 23S rRNA

PleuromutilinRetapamulin

05/23

06/23

07/23

08/23

HIT-rate (WDF, n=189)>>366X~4

M. smegmatis : 78%S. aureus : 68% E. coli : 44% C. albicans : 31%

HIT-rate (MEF, n=29)>>(+143)light/dark

M. smegmatis : 98% / 78%S. aureus : 58% / 43% E. coli : 20% / 0%C. albicans : 13% / 0%

HIT-rate (ABF, n=111)>>800+

M. smegmatis : 87%S. aureus : 19% E. coli : 8% C. albicans : 30%

HIT-rate (TEF, n=0)>>400+

M. smegmatis : --S. aureus : --E. coli : --C. albicans : --

HIT-rate (SBF, n=0)>> 201

M. smegmatis : --S. aureus : --E. coli : --C. albicans : --

Total: 2700+09/23

0

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AMP 40 AMX 40 VAN 40 INH10 EMB 20 PZD 40 MOXI 0.5 RIF 10 LIN 5 TET 20 CHLO 40 ERY 40 STREP 20

CYSERIN 2

Zone

of i

nhib

ition

(mm

) M. smegmatis (24 hrs) Phenotypic Array for Standard Antibiotics

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18/22 15/22

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1/22

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0/22

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AMP 40 AMX 40 VAN 40 INH10 EMB 20 PZD 40 MOXI 0.5 RIF 10 LIN 5 TET 20 CHLO 40 ERY 40 STREP 20

CYSERIN 2

Zone

of i

nhib

ition

(mm

) Ery-M. smegmatis (24 hrs) Phenotypic Array for Standard Antibiotics

18/22

12/22

1/22 0/22 0/22 0/22 1/22

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0/22 0/22 0/22 1/22

17/22

0/22

11/23

12

Reverse Phase C-18

Size Exclusion LH-20

Bioassay

12/23

13

BCG cell (GFP)Drug treatment

Quantitative measurements of Cell viability and growth13/23

Mass Spec1D Proton NMR13C, 15N,HSQC, HMBC, HMQC, COSY, TOCSY, ROESY, NOESYetc…14/23

15/23

Miguel A. MatillaGeorge P. C. SalmondDepartment of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW

16/23

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23/23

Project Team MembersSamuel Yaw Aboagye (2009-2011)

Priscilla Koduah (2010-2011)

Vincent Amarh (2011-2012)

Clement Opoku-Temeng (2012-2013)

Samuel Mawuli Adadey (2012- )Gloria Baaba Arkaifie (2013- )Arnold Abraham (2013 - )Precious Cramer (2013 - )

Mentorship and Project SupportDr. Paul A. LarteyLaGray ChemicalCompany – NsawamGHANA

Collaborators

University of CambridgeDr. Finian Leeper

Imperial College LondonDr. Brian Robertson

ETH-Zurich Prof. Ruedi AebersoldOlga SchuberMichael Zimmermann

University of Maryland -CPProf. Herman Sintim

UG-NMIMRProf. Dorothy Yeboah-Manu

FundingDAAD-GermanyGrand Challenges-CanadaTWAS-ItalyIFS-SwedenEMBO/SNF-SwissGates Foundation/NMIMRCAPREx/Alborada