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Antimicrobial Materials

Surface activity as a tool for antimicrobial


material design

Vignesh Nandakumar
EMA 4121

04/09/2018

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Why is antimicrobial materials a hot topic?
Microbes are smart… and experienced…

• Increasing number of Antimicrobial Resistant Strains (AMR)


• Prevention of a disease is far better than finding a cure!

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Antibiotics Resistance

Decreasing Increasing
pipeline of antibiotic
antibiotics resistance strains

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Antimicrobial resistance

Eg., MRSA, XDR – TB, Gonorrhea

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Super bugs….
Clostridium difficle: CDC fact sheet
• 250,000 Infections per year
• 14,000 deaths
• $ 1B Excess medical costs per year
• Threat level - Desperate

Solution: Poop in a Pill…

Learn more @ bostonchildrens.org/fecaltransplant

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Procrastination at a whole new level…

Current
technology against
AMR/MDR bugs

Things you read about and feel happy as a


Graduate student…. Thou aren’t alone!!!

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Need for alternate technologies
Antimicrobial materials - design criteria (post 2010) :
1) Avoid approaches with extreme specificity – triggers
site specific mutations
2) Non toxic to mammalian cells
3) Weighing kill necessity – Extremely important!
4) Evaluate new generic target sites

Surface actives (surfactants) – Promising antimicrobial agents


Common mechanisms of action
1) Membrane disruption/ permeabilization
2) Protein denaturation
3) Removal based reduction in bacterial counts from
surfaces
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Surfactants (phospholipids) and
polymers (proteins)
an integral part of The cell membrane

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Surfactants and polymers can also destroy cells
Attacking the lipids
• Homogenous surfactants
• CTAB, Tweens, SDS, Triton X100
• Most genetic engineering protocols use surfactants for extraction of
proteins/intracellular components
• Cationic molecules
• Cationic polymers – polyallylamine, PAMs, PEI
• QAC’s, chlorhexidine etc.,

Attacking proteins
• Surfactants
• Unfolding and denaturation – SDS is a common example
• Metal nanoparticles and metal ions
• Thiol group interactions with metal surfaces (protein denaturation)

Attacking intracellular environment


• Surfactant partitioning/permeabilization – (TX- 100, tweens etc..)

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Non – Kill based antimicrobial approaches
Removal based disinfection
 Disinfection does not necessarily have
to involve kill – although this is the
most common mode
 Removal based alternatives have a lot
of potential – Particularly where kill
based approaches are ineffective
Figure: Proper hand wash protocol

Anti – adhesion systems


 Prevent adhesion of microbes to surfaces
using physical and chemical patterns

 Examples: Pluronics, PEO – PPO – PEO


coatings, Sharklet™

Figure: Sharklet ™ patterns

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Motivation for removal approaches
Motivation: Reduce the rate of touch transfer of pathogens
Table: Persistence of clinically relevant bacteria on inanimate dry surfaces4
Role of substrates in infection transfer
Type of organism Duration of persistence
 Pathogens persist on inanimate (range)
surfaces for long durations (hours to Escherichia coli 1.5 hours to 16 months
months)1,4 Staphylococcus aureus 7 days – 7 months
 Hands rank as the #1 substrate for Salmonella typhi 6 hours – 4 weeks
infection transmission (in a non-clinical Mycobacterium tuberculosis 1 day – 4 months
environment)1
 Projected disinfectant market – USD 8.0 Enterococcus spp. 5 days – 4 months
billion (2021)2 Clostridium difficile (spores) 5 months

Existing approaches for Hand hygiene


Comparison of log reduction in pathogens

 Surfactants + wash hydrodynamics  Antibacterial soaps Base 10 Log Reduction Surviving


organism
(~1.1 L.R (92%)5,6) (mostly bacteria limited)
 Physical wash off and removal  Enhanced spatial penetration + 1-log reduction 90% 1 in 10

kill of bacteria (on skin) 2-log reduction 99% 1 in 100


 Studies indicate 95% of the  FDA’s ruling in September 2016 bans
population do not wash hands the use of 19 antimicrobial actives 3-log reduction 99.9% 1 in 1000

enough to kill pathogens!!!!3 currently employed in hand washing7


4-log reduction 99.99% 1 in 10000

Alternate approaches in hand washing and substrate disinfection – A critical need!!


Summary
Role of surfactants and polymers in cell structure and
strategies to prevent infection transmission

• Maintaining cell structure


• Antimicrobial agents – Cell membrane permeabilizing/disrupting
agents
• Antimicrobial coatings
• Anti biofouling coatings – PEO/zwitterions based mixed polymer
systems
• Cleansers

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