Antibiotic Resistance https://upload.wikimedia.org/wikipedia/commons/2/20/Antibiotic_sensitvity_and_resistance.

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https://upload.wikimedia.org/wikipedia/commons/2/20/Antibiotic_sensitvity_and_resistance.JPG

Tanjheela Jahan
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 Antibiotic Resistance
1928 Discovery of penicillin
1960 Golden era of Antibiotics
2000 Beginning of resistance era
2019 The world is on the verge of ‘’post antibiotic era’’

Bacteria: are clever, they learned how to fight antibiotics

Human: helped bacteria by overusing and misusing antibiotics
How Bacteria grows resistance?

• By degrading/altering the antibiotic (e.g. B lactamases

alters Penicillin)
• By modification of drug target (e.g. modification of cell
wall proteins)
• By increasing drug efflux (e.g. Tetracyclines)
• By decreasing drug influx (e.g. Aminoglycoside)
• By developing antibiotic resistant genes (e.g. through
plasmid)
How Bacteria grows resistance?

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 How Nanoparticles can help?
Can have antibacterial
property (e.g. Ag NPs) 2
NPs
Can be used as a vehicle
to deliver antibiotic (eg.
Liposomes, micelles,
dendrimers)
Can be coupled with existing
antibiotics for synergistic effect (Au
NPs combined with Ampicillin
reduces MIC of Ampicillin)1
-directly interacts with bacterial cell wall
-trigger innate and adaptive host immune
response
-generate oxygen species that are reactive
(ROS)
-interact with bacterial DNA and/or proteins
and inhibit biofilm formation.
Biofilms: Big challenge
Penetration
in Biofilms

Targeted
NPs can delivery to
inhibit the
help notorious
gene

Coating of
medical
devices
with NPs
Targeting Challenges……
Overcoming the physical and chemical barriers is challenge for the
nanoparticles. This can be overcome by both Active targeting or Passive
Targeting.
 Passive Targeting using NPs

❑EPR Effect
❑pH
❑Light
❑Temperature
Active Targeting using NPs

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Design Challenge……
• Small sized and spherical shaped Nps facilitate uptake. For biofilm
penetration, needle shaped NPs are suitable. Tranmission Electron
Microscopy and Scaning Electron Microscopy can be used for
characterization of size and shape of NPs.
• Materials need to be nontoxic to human and selectively kills bacteria cells
only. In vitro cell survival assay and checking the autophagy level from the
cell lysates can be used to test the toxicity of the particles. Also checking
the MIC of the particles by measuring the zone of inhibition (disc diffusion
method) will be helpful.
• Among In Vivo tests, pharmacokinetics study to measure the
biodistribution, half-life, elimination rate, therapeutic index needs to be
performed.
Success Stories……
• Silver is one of the FDA approved potent antimicrobial agents for
coating catheters. Silver nanoparticles show promising result in
eradicating infection of urinary catheters with better efficacy. 4

For the 2-year period following the

introduction of the silver
alloy/hydrogel-coated urinary
catheter, the overall rate of UTI per
1000 catheter-days, for the units
under surveillance, declined
significantly. 7
 Success Stories……
FDA approved Liposomal Amikacin
for treatment of NTM infection.
Liposome-encapsulated amikacin
(Arikayce), can penetrate the
biofilms formed in non-
tubercoulosis mycobacterium
infection, and is taken up
by immune system cells called
macrophages. 5, 8
Success Stories……
Gold nanoparticles combined with other antibacterial agents (ampicillin,
streptomycin, and kanamycin) shows better efficacy by decreasing the MIC
of the antibiotics. Also, conjugation of antibiotic with gold nanoparticles
result in better stability of the drug.6

Bactericidal activity (S.aureas) by agar well diffusion assay for

free antibiotics and their respective GNPs conjugated form.
Success Stories……
Ashley N. Brown et al showed that functionalization of AuNP
with ampicillin makes them potent and resulted in disruption
of the antimicrobial mechanism of multiple-drug-resistant
bacteria. They found that AuNps alone were nontoxic to
bacterial cells but AuNP functionalized with ampicillin (AuNP-
AMP) were bactericidal.
Success Stories……
Antibody conjugated Nps can be used to detect
pathogenic bacteria. This can help to quick and
accurate diagnosis of bacterial infections.
Future…
Antibiotic resistance is a natural process. Bacteria mutates and learn to
fight antibiotics. With current success and continuous study with
nanoparticles, we can find ways to fight the resistant bacteria.

However, we need to be sensible in using antibiotics. Misuse and

overuse of antibiotics can lead us to the ‘’post antibiotic era’’. We
should not let it be.
Reference:
1. Brown, A. N., Smith, K., Samuels, T. A., Lu, J., Obare, S. O., & Scott, M. E. (2012). Nanoparticles
functionalized with ampicillin destroy multiple-antibiotic-resistant isolates of Pseudomonas aeruginosa and
Enterobacter aerogenes and methicillin-resistant Staphylococcus aureus. Applied and environmental
microbiology, 78(8), 2768–2774. doi:10.1128/AEM.06513-11
2. Burdușel, A. C., Gherasim, O., Grumezescu, A. M., Mogoantă, L., Ficai, A., & Andronescu, E. (2018).
Biomedical Applications of Silver Nanoparticles: An Up-to-Date Overview. Nanomaterials (Basel,
Switzerland), 8(9), 681. doi:10.3390/nano8090681
3. Antibacterial drug discovery in the resistance era. Eric D. Brown & Gerard D. Wright. N at u r e | vo l 5 2 9 |
2 1 Ja n uary 2 0 1 6
4. Singha P, Locklin J, Handa H. A review of the recent advances in antimicrobial coatings for urinary
catheters. Acta Biomater. 2017;50:20–40. doi:10.1016/j.actbio.2016.11.070
5. https://copdnewstoday.com/copd-experimental-treatments__trashed/arikayce/
6. T.-K. Nguyen, H. T. T. Duong, R. Selvanayagam, C. Boyer, N. Barraud, Sci. Rep. 2015, 5, 18385.
Reference:
7. Rupp, M.E., Fitzgerald, T., Marion, N.D., Helget, V., Puumala, S.S., Anderson, J.R., & Fey, P.D. (2004). Effect of
silver-coated urinary catheters: efficacy, cost-effectiveness, and antimicrobial resistance. American journal of
infection control, 32 8, 445-50 .
8. https://www.businesswire.com/news/home/20140326005630/en/Insmed-Announces-Results-Phase-2-
Clinical-Trial
9. Antibody conjugated Nps can be used to detect pathogenic bacteria. This can help to quick and accurate
diagnosis of bacterial infections