Download Antibiotic-resistant Bacteria Selective Extermination

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Antibiotic-resistant Bacteria
Selective Extermination
through NanoTargeting
Stan Willems
[email protected]
Motivation
Antibiotics have made it possible to cure and prevent infections
in humans and animals. Unfortunately, antibiotic resistance (AR)
has developed among bacteria due to society overusing antibiotics.
Antibiotics and genes in waste-water encoding for antibiotic
resistance are discharged from areas such as hospitals into
environmental reservoirs, allowing for further spreading of antibiotic
resistance throughout discharge routes[1]. A platform on which ARB
can be selectively captured is therefore a novel way for preventing
the spread of ARB and their resistance encoding genes at the
source, for example from hospital waste-water. Bacterial cells can
be captured via cell-targeting (at the cell surface)[2] by translating
techniques already used for targeting tumour cells in a clinical
setting. A nanoplatform based on these targeting capabilities and
using non-covalent and orthogonal interactions (for example with
cyclodextrin surfaces[3]) will allow for selective capturing of target
ARB and provide a controlled release mechanism of the ARB in a
separate environment where they can be exterminated.
Technological challenge
Removal of ARB from water using specific targeting molecules that
selectively interact and bind with ARB is new principle within wastewater treatment technology. The challenge within this project is the
immobilization of bacteria in flow-setting on a functionalized (nano)
platform. Multivalency is key to improving binding speed of targeted
bacteria to the nanoplatform. Furthermore, achieving specificity for
ARB capture with the targeting molecules attached to the (nano)
platform is also a challenge. Bacterial binding experiments to
validate interaction with targeting molecules can be carried out
using functionalized glass substrates. Intermediary molecules can
be microcontact printed (µCP) in a certain pattern on these surfaces
as a proof-of-concept method.
Antibiotic-resistant
bacteria
Selective targeting
Recyclable
Nanoplatform
Isolation
&
Extermination
Fig 1. Functionalized nanoplatform based on cyclodextrin layers on a glass surface
immobilizing bacterial cells with a targeting peptide. The size of bacteria compared to
targeting groups is not to scale: bacteria are approximately 1000 times larger. Confocal microscopy image courtesy of IMI group, LUMC.
Research goals
Important research objectives to be met in creating a nanoplatform
that can specifically target and immobilize ARB in hospital waste
water are: 1) high affinity interactions of targeting molecules
of the functionalized nanoplatform with bacterial cells through
multivalency to allow for quick immobilization as water flows past,
2) reversible interactions to allow for release of bacteria in a separate
environment followed by extermination and subsequently reusability
of the nanoplatform, 3) validation of tethering targeting molecules
to nanoplatform, 4) researching possibilities for specific targeting of
ARB in waste-water, and 5) validation of created nanoplatforms in
model waste-water streams
Scale-up
Implementation in waste-water flow devices
Fig 2. Project approach shown on the left and concept of how targeting molecules
tethered to a surface could be used in waste-water flow device. Important is to realize
that the scale of bacteria is approximately 1000 times larger than the targeting molecules depicted.
www.wetsus.eu
www.wageningenur.nl
[1] Chastre, J. (2008). CMI 14: 3-14.
[2] Mick M. Welling, Anton Bunschoten, Joeri Kuil, Rob G. H. H. Nelissen, Freek J. Beekman, Tessa
Buckle, and Fijs W. B. van Leeuwen (2015). Bioconjugate Chemistry 26 (5), 839-849
[3] Gonzalez-Campo, A., S. H. Hsu, et al. (2010). J. Am. Chem. Soc 132(33): 11434-11436.
S.B.J. Willems (MSc), prof.dr. A.H. Velders,
dr. F.W.B. Van Leeuwen, dr. L. Hernandez-Leal