Photoswitchable Bactericide

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.

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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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.