A significant challenge in the development of effective antibacterial agents arises from bacterial pathogens that have evolved to inhabit mammalian cells, such as phagocytic macrophages. Within these intracellular safe havens the bacteria reproduce and form a repository, and are able to evade the host immune response as well as a number of antibiotic drugs. Therefore, there is a great need to develop antibiotics with the ability to enter mammalian cells and target intracellular pathogens at their specific sub-cellular site. We have developed a class of molecules, cationic amphiphilic polyproline helices (CAPHs), that effectively enter mammalian cells through both direct transport and endocytosis. We have determined that CAPHs also have potent broad-spectrum antibacterial activity. This dual mode of action, non-lytic antibacterial activity with the ability to localize within mammalian cells, provided us with agents with a pronounced ability to target and kill pathogenic intracellular bacteria within human macrophages.

Stalking elusive pathogenic bacteria with cationic amphiphilic polyproline helices: Diving into human cells to treat infections

ACS Spring 2022

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