Abstract
Bacterial infections caused by intracellular pathogens are difficult to control. Conventional antibiotic therapies are often ineffective, as high doses are needed to increase the number of antibiotics that will cross the host cell membrane to act on the intracellular bacterium. Moreover, higher doses of antibiotics may lead to elevated severe toxic effects against host cells. In this context, antimicrobial peptides (AMPs) and cell-penetrating peptides (CPPs) have shown great potential to treat such infections by acting directly on the intracellular pathogenic bacterium or performing the delivery of cargos with antibacterial activities. Therefore, in this mini-review, we cover the main AMPs and CPPs described to date, aiming at intracellular bacterial infection treatment. Moreover, we discuss some of the proposed mechanisms of action for these peptide classes and their conjugation with other antimicrobials.
Highlights
Over the years, bacteria have been adapting to survive, become resistant to drugs, and make the host’s phagocytes their home (Cornejo et al, 2017)
Conventional antibiotics used in treatments against extracellular bacteria have reduced permeability in intracellular bacterial infections (Proctor et al, 2006; Lehar et al, 2015)
Another applicability of cell-penetrating peptides (CPPs) includes the transport of antibiotics into the host cell, as these antimicrobials can be useful against intracellular bacteria, but have little permeability
Summary
Bacteria have been adapting to survive, become resistant to drugs, and make the host’s phagocytes their home (Cornejo et al, 2017). CPPs have a high permeability rate, cross the membrane of different cell types, present low cytotoxicity and do not activate the host’s immune response (Ruseska and Zimmer, 2020) These peptides can either exert a direct antibacterial mechanism or perform the delivery of bioactive molecules, including other antimicrobial agents and PNAs (Reissmann, 2014). The bacterium secretes effector proteins into the cytoplasm to modulate the actin cytoskeleton, polymerizing the actin, forming a pseudopod and allowing the bacteria’s entry into the cytoplasm (Veiga and Cossart, 2006; Ó Cróinıń and Backert, 2012) Another problem is that bacterial infections caused by intracellular pathogens are incredibly difficult to eradicate (Cossart and Sansonetti, 2004), as the antibiotics’ concentration internalized in host cells is lower than their minimum inhibitory concentration (MIC) (Harish and Menezes, 2015). The increase in resistance to multiple drugs reinforces the urgent need to develop new intracellularly active antibacterial agents capable of overcoming the low cellular permeability of the antimicrobials currently used (Weissman et al, 2016)
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