Cell-Penetrating Antimicrobial Peptides with Anti-Infective Activity against Intracellular Pathogens

Abstract

Cell-penetrating peptides (CPPs) are natural or engineered peptide sequences with the intrinsic ability to internalize into a diversity of cell types and simultaneously transport hydrophilic molecules and nanomaterials, of which the cellular uptake is often limited. In addition to this primordial activity of cell penetration without membrane disruption, multivalent antimicrobial activity accompanies some CPPs. Antimicrobial peptides (AMPs) with cell-penetrability exert their effect intracellularly, and they are of great interest. CPPs with antimicrobial activity (CPAPs) comprise a particular class of bioactive peptides that arise as promising agents against difficult-to-treat intracellular infections. This short review aims to present the antibacterial, antiparasitic, and antiviral effects of various cell-penetrating antimicrobial peptides currently documented. Examples include the antimicrobial effects of different CPAPs against bacteria that can propagate intracellularly, like Staphylococcus sp., Streptococcus sp., Chlamydia trachomatis, Escherichia coli, Mycobacterium sp., Listeria sp., Salmonella sp. among others. CPAPs with antiviral effects that interfere with the intracellular replication of HIV, hepatitis B, HPV, and herpes virus. Additionally, CPAPs with activity against protozoa of the genera Leishmania, Trypanosoma, and Plasmodium, the etiological agents of Leishmaniasis, Chagas’ Disease, and Malaria, respectively. The information provided in this review emphasizes the potential of multivalent CPAPs, with anti-infective properties for application against various intracellular infections. So far, CPAPs bear a promise of druggability for the translational medical use of CPPs alone or in combination with chemotherapeutics. Moreover, CPAPs could be an exciting alternative for pharmaceutical design and treating intracellular infectious diseases.

Antimicrobial Drug Resistance in Poultry Production: Current Status and Innovative Strategies for Bacterial Control

“…They evolved as a host defense mechanism against microorganisms and are important to innate immunity [17,61]. Generally, AMPs are small molecules (<10 kDa) with 12-50 amino acids, presenting broad-spectrum antimicrobial activity against bacteria, fungi, protozoa and viruses [62,63]. AMPs have several advantages: they can present several modes of action, are easily degraded in nature, present reduced accumulation, contribute to the enhancement of host immunity, have the ability to neutralize the activity of many microorganisms and seem to present a low resistance frequency [17,64].…”

Cell Penetrating Peptides: Classification, Mechanisms, Methods of Study, and Applications

“…It is not surprising that many AMPs can behave as CPPs as these two groups often share structural and physicochemical characteristics that, depending on the experimental conditions, are balanced between their functions: membrane disruption/ perturbation and cell penetration. [71,79] Many human proteins are also a source of CPPs, possessing the advantage of minimizing possible in vivo immunogenicity and toxicity effects. Many proteins-derived CPPs have been identified such as VectoCell, [80] Lactoferrin, [29] Sim-2, [81] 2IL-1a.…”

Neglected Zoonotic Diseases: Advances in the Development of Cell-Penetrating and Antimicrobial Peptides against Leishmaniosis and Chagas

“…To overcome these deficiencies, AMPs and CPPs could become a promising alternative for pharmaceutical design and treatment of intracellular infectious diseases. Current studies reflect interesting antimicrobial properties of these peptides against intracellular bacteria, virus, and protozoan genera Leishmania, Trypanosoma, and Plasmodium, the etiological agents of the main forms of leishmaniases, trypanosomiasis, and malaria, respectively [8,14].…”

“…That is, the distribution of various types of molecules: proteins, peptides, nucleic acids, liposomes, nanoparticles, or drugs. This group of natural or synthetically generated peptides has the ability to translocate through cell membranes; in many cases, they do so at low concentrations and without significantly damaging the cell membrane [8]. The entry mechanism can be through an indirect endocytosis (energy dependent) or a direct entry (energy independent) that can be associated with membrane toxic activity, or even through both mechanisms occurring simultaneously.…”

“…These are promising strategies to increase therapeutic efficacy, avoiding the development of toxicity or resistance; or in a controlled way [6]. The members of this group of peptides share similar physicochemical properties, but their mechanisms of action can vary, thus making it possible to differentiate them into two subgroups: antimicrobial peptides (AMPs) and cell penetrating peptides (CPPs) [7,8]. This review presents the novelties of these peptide molecules, their potential to replace traditional antibiotics, and their activity and mechanisms of action against two of the most relevant neglected zoonoses: leishmaniosis and Chagas disease.…”