Nanomaterial with “Light Switch” Kills Gram-negative or Gram-positive Bacteria
Healthcare-associated infections are a common problem in suppurating
wound care, as is the rise in multi-drug resistant bacteria. In order to
effectively and selectively combat bacterial infections, a team of
researchers have developed a bactericidal nanomaterial equipped with a
photochemical “light switch” that can be directed either against
Gram-positive or Gram-negative bacteria. As the team report in their
study published in Angewandte Chemie, its effectivity against MRSA can be extended to other selective bacterial infections.
Antibiotic-resistant infections have become an urgent public
health concern, particularly in hospital settings. Many of the bacterial
species in question are widespread in nature, but can cause much more
serious, sometimes untreatable, infections in immunocompromised
patients. Bactericidal materials offer a new approach to combating
healthcare-associated infections that does not rely on antibiotics.
Mrinmoy De and colleagues from the Indian Institute of Science in
Bengaluru, India, have now succeeded in producing a
UV-visible-light-responsive nanomaterial that can be switched to target
either Gram-positive or Gram-negative bacteria.
© Wiley-VCH, re-use with credit to 'Angewandte Chemie' and a link to the original article.
Both bacteria types have very different outer membrane structures and
composition. Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), have a bacterial membrane majorly composed of peptidoglycans. In contrast, Gram-negative bacteria, including Pseudomonas aeruginosa,
another healthcare-associated bacterium with problematic resistance to
broadband antibiotics, has both inner and outer membrane mainly composed
of phospholipids with a thin peptidoglycan layer. “It is important to
achieve strain-selective bactericidal activity,” says De.
To achieve a bactericidal agent that could selectively interact with
both chemical surfaces, the team designed a functionalized nanomaterial
made of molybdenum disulfide (MoS2) with azobenzene moieties
to which positively charged quaternary amino groups were attached. While
MoS2 is a bactericide and the quaternary amino groups allow membrane
depolarization, the azobenzene moieties introduce a light-driven switch
in the nanostructure from an elongated trans into a curved cis form to
create selective surface interactions.
The team used several chemical probes and optical measurements to
determine that both the cis and trans forms of the nanomaterial killed
bacteria, albeit in very different ways. For the Gram-negative P. aeruginosa,
the trans form depolarized the bacterial membrane and pierced it
thoroughly. This allowed the MoS2 nanomaterial to generate intracellular
reactive oxygen species and kill the bacteria. Conversely, the
Gram-positive MRSA strain responded to the cis form more effectively. In
this case, the cell wall was damaged and ruptured by specific
interactions.
By simply “flipping” the UV switch from the trans ground state to the
cis state, the team were able to control selectivity for either
bacterial type. They demonstrated the efficacy of their nanomaterial by
successfully healing MRSA-infected wounds in mice models. The wounds
completely closed after 10 days when treated with the cis reagent, while
usual antibiotic treatment with vancomycin was not healing fast.
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About the Author
Dr. Mrinmoy De is an
Associate Professor at the Department of Organic Chemistry, Chemical
Science Division, Indian Institute of Science in Bengaluru, Karnataka,
India. His group is interested in the synthesis of laterally size
controlled 2D single or thin-layer molecular assemblies by chemical
synthesis or processing from their corresponding precursor to explore
the various supramolecular applications including molecular recognition,
antimicrobial activity, sensing and catalytic applications.
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