Current and potential applications of host-defense peptides and proteins in urology.

Joey Chor Yee Lo,Dirk Lange

doi:10.1155/2015/189016

Abstract

The use of antibiotics has become increasingly disfavored as more multidrug resistant pathogens are on the rise. A promising alternative to the use of these conventional drugs includes antimicrobial peptides or host-defense peptides. These peptides typically consist of short amino acid chains with a net cationic charge and a substantial portion of hydrophobic residues. They mainly target the bacterial cell membrane but are also capable of translocating through the membrane and target intracellular components, making it difficult for bacteria to gain resistance as multiple essential cellular processes are being targeted. The use of these peptides in the field of biomedical therapies has been examined, and the different approaches to using them under various settings are constantly being discovered. In this review, we discuss the current and potential applications of these host-defense peptides in the field of urology. Besides the use of these peptides as antimicrobial agents, the value of these biological molecules has recently been expanded to their use as antitumor and anti-kidney-stone agents.

Highlights

The use of antibiotics can be dated back to the 1930s, when the sulfonamide Prontosil was introduced as the first commercially available antibiotic [1]
Even stated “. . .we had essentially defeated infectious diseases and could close the book on them. . .” [3]. This statement looked true at that time, it was soon refuted when pathogenic bacteria with resistance against conventional antibiotics become increasingly prominent by the end of the 20th century; bacteria had gained resistance to multiple drugs [4]
The rise in multidrug resistant (MDR) bacteria became alarming, with a prevalence rate increase of 57% from the 1950s to the 2000s, with more resistance observed towards drugs that had been used for humans and animals for the longest time [4,5,6]

Summary

Introduction

The use of antibiotics can be dated back to the 1930s, when the sulfonamide Prontosil was introduced as the first commercially available antibiotic [1]. Antimicrobial peptides (AMPs) are ancient defense molecules of the innate immune system that has gained substantial attention over recent years [4, 7] These peptides are found within a wide variety of species, including bacteria, insects, fungi, amphibians, birds, crustaceans, fishes, mammals, and humans, and can be obtained from many different sources, such as neutrophils, macrophages, and epithelial cells [7,8,9]. Unlike current antibiotics, these AMPs have multiple sites as targets rather than single genes or proteins [4] These peptides are mainly known for their ability to disrupt the cell membrane of target organisms, they are known for their ability to translocate through the cell membrane and alter other essential cellular activities and promote immune responses, including but not limiting to upregulating or downregulating DNA, RNA, and protein. KWCFRVCYRGICYRKCR-NH2 KRWRIRVRVIRKC-NH2 RWKRWWRRKK RKKRWWRRKK GIGKFLHSAKKFGKAFVGEIMNS-NH2 KWKLFKKIEKVGQNIRDGIIKAGPAVAVVGQATQIAK-NH2 KWKVFKKIEKMGRNIRNGIVKAGPAIAVLGEAKAL-NH2 Most potent one analyzed: H-(Nlys-Nspe-Nspe)4-NH2 DHYNCVSSGGQCLYSACPIFTKIQGTCYRGKAKCCK-NH2 Many OPN-derived peptides were analyzed; one of the more promising ones being OPN-derived peptide D9: ADAAADDAAADAAADDAA-NH2

C H3 C H2 C

Conclusions

Findings

Conflict of Interests