Staphylococcal Bacterial Persister Cells, Biofilms, and Intracellular Infection Are Disrupted by JD1, a Membrane-Damaging Small Molecule
Jamie L. Dombach, Joaquin L. J. Quintana, Corrella S. Detweiler
Abstract
Untreatable bacterial infections are a critical public health care issue. In addition to increasing antibiotic resistance, bacteria that are in slow-growing or nongrowing states, or that live inside mammalian cells, are typically insensitive to clinical antibiotics and therefore difficult to eradicate. Bacterial cell membranes have been proposed as potential novel antibiotic targets that may be vulnerable in these difficult to treat cell types because cell membranes are always present and performing essential functions. The small molecule JD1 was previously shown to disrupt Gram-negative bacterial cell membranes. Here, we show that it also disrupts the cell membrane of Gram-positive bacteria and reduces viable bacteria within persister populations, biofilms, and mammalian cells. These observations demonstrate the importance of testing novel compounds under infection-relevant conditions, because their potency against rapidly growing cells may not reveal their full potential.