Converting Natural Biomass to Amphiphilic Antimicrobial

Polymers in Solution and on Surfaces

Tang Polymer Research Group @ USC, Columbia, SC. URL: http://www.tangpolymer.org

Motivation

Antimicrobial Surfaces Bacterial infectious diseases have

become a widespread health care crisis.

Most antibiotics used today are prone to

bacterial resistance.

There is a great need for a resilient

platform to develop antimicrobial agents

to face the evolving microbial resistance.

Antimicrobial peptides are a

class of natural molecules

acting to defend animals from

emerging pathogens.

They typically target bacterial

cell membranes.

Antimicrobial polymers are

synthetic counterparts of

them.

An economical method was developed to prepare cationic resin acid

compounds at kilograms scale without any chromatography purification.

Strong antimicrobial activities against MRSA strains and minimum

toxicities towards mammalian cells.

Molecular dynamics simulations and dye-leakage assays indicated a

membrane-disruptive mechanism of action.

Medically relevant antimicrobial and anti-biofilm coatings were

developed by grafting resin acid derived compounds and

polymers on surfaces.

The surfaces showed antimicrobial

and antibiofilm properties against

Gram (-) E. Coli and Gram (+) S.

aureus bacteria.

Quaternary ammonium containing cationic materials can be conveniently

synthesized from biomass derived resin acids and itaconic acid and can

be applied as antimicrobial agents in solution and on surfaces.

Strong antimicrobial and anti-biofilm properties with minimum toxicities

indicate that these materials are promising for biomedical applications.

Dr. Kristen P. Miller

Dr. Juhua Zhou

Dr. Jerry Ebalunode

Dr. Jifu Wang

Dr. Kejian Yao

Dr. Perry Wilbon

S. Parker Singleton

Mitra S. Ganewatta,† Pegah Mehrpouya-Bahrami,§ Md Anisur Rahman,† Louis N. Mercado,† Yung P. Chen,‡

Mitzi Nagarkatti,§ Prakash Nagarkatti,§ Alan W. Decho,‡ and Chuanbing Tang†*

†Department of Chemistry and Biochemistry, ‡Department of Environmental Health Sciences, §Department of Pathology, Microbiology and Immunology (School of Medicine), University of South Carolina, Columbia, SC 29208

Antimicrobial Polymers

Natural biomass derived chemicals show the potential to be modified into

amphiphilic molecules with antimicrobial properties.

Objectives

Hydrophobic Cationic

Convert natural resin acids and itaconic acid into cationic compounds

and polymers that are soluble in water.

Modify solid substrate surfaces using the biomass derived cationic

polymers.

Introduction

Itaconic acid derived cationic and hydrophobic random polymers were

synthesized via RAFT polymerization and post-polymerization

modifications. Conclusions

Acknowledgements

22 24 26 28 30

Elution Time (min)

Đ = 1.26

Mn= 3200 g/mol

0 100 200 300 400 5000

20

40

60

80

100

% H

em

oly

sis

Polymer Concentration (µg/mL)

S. aureus strain Compound 1 Polymer 2

MIC (µg/mL)

CA-MRSA ATCC BAA-1717 5.0 9.9

HA-MRSA ATCC BAA-29213 6.0 14.0

CA-MSSA ATCC BAA-1718 7.3 8.8

MRSA-252 ATCC BAA-1720 4.8 19.0

HC50 (µg/mL) > 500 > 492 Selectivity index (HC50/MIC) > 68 > 26

0

10

20

30

40

50

60

70 B cells

CD8 T cells

poly

mer

2

com

pound 1Pe

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nt

of

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ll p

op

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tio

n

in s

ple

no

cy

tes

In-vitro

In-vivo

contr

ol

poly

mer

2

com

pound 1

contr

ol

poly

mer

2

com

pound 1

contr

ol

CD4 T cells

• Hydrophobic ring structure

• Bulkiness - steric effects

• Carboxylic acid

• Conjugated diene

• Anhydride

Key Features: • Polymerizable acrylate group

• Carboxylic acid

• Anhydride

Ganewatta M. S.; Tang C. Polymer, 2015, 63, A1-A29.

The cationic surfaces promoted

human dermal fibroblast growth.

Ganewatta M. S.; Miller K. P.; Singleton S. P.; Mehrpouya-Bahrami P.; Chen Y. P.; Yan Y.; Nagarkatti M.; Nagarkatti P.; Decho A. W.;

Tang C. Biomacromolecules, 2015, 16, 3336–3344.

10 20 300

2

4

6

8

10

12

Dia

mete

r o

f In

hib

itio

n Z

on

e (

mm

)

Polymer Concentration (µg/disk)

S. aureus

E. coli

Ganewatta M. S.; Chen Y. P.; Wang J.; Zhou J.; Ebalunde J.; Nagarkatti M.; Decho A. W.; Tang C. Chem. Sci., 2014, 5, 2011-2016.