Antibiotic-cell-penetrating peptide conjugates targeting challenging drug-resistant and intracellular pathogenic bacteria

The failure to treat everyday bacterial infections is a current threat as pathogens are finding new ways to thwart antibiotics through mechanisms of resistance and intracellular refuge, thus rendering current antibiotic strategies ineffective. Cell-penetrating peptides (CPPs) are providing a means to improve antibiotics that are already approved for use. Through coadministration and conjugation of antibiotics with CPPs, improved accumulation and selectivity with alternative and/or additional modes of action against infections have been observed. Herein, we review the recent progress of this antibiotic-cell-penetrating peptide strategy in combatting sensitive and drug-resistant pathogens. We take a closer look into the specific antibiotics that have been enhanced, and in some cases repurposed as broad-spectrum drugs. Through the addition and conjugation of cell-penetrating peptides to antibiotics, increased permeation across mammalian and/or bacterial membranes and a broader range in bacterial selectivity have been achieved.