Peptidomimetics as Potential Anti-Virulence Drugs Against Resistant Bacterial Pathogens.

The uncontrollable spread of superbugs calls for new approaches in dealing with microbial-antibiotic resistance. Accordingly, the anti-virulence approach has arisen as an attractive unconventional strategy to face multidrug-resistant pathogens. As an emergent strategy, there is an imperative demand for discovery, design, and development of anti-virulence drugs. In this regard, peptidomimetic compounds could be a valuable source of anti-virulence drugs, since these molecules circumvent several shortcomings of natural peptide-based drugs like proteolytic instability, immunogenicity, toxicity, and low bioavailability. Some emerging evidence points to the feasibility of peptidomimetics to impair pathogen virulence. Consequently, in this review, we shed some light on the potential of peptidomimetics as anti-virulence drugs to overcome antibiotic resistance. Specifically, we address the anti-virulence activity of peptidomimetics against pathogens' secretion systems, biofilms, and quorum-sensing systems.

Peptides as a therapeutic strategy against Klebsiella pneumoniae.

Increasing levels of resistance to conventional antibiotics have led to a search for new therapeutic options against bacterial infections. Klebsiella pneumoniae is considered a world health problem due to high levels of mortality associated with resistance to multiple antibiotics. Antimicrobial peptides (AMPs) have showed activity against this bacterium, which makes them a promising alternative in tackling resistance. In this article, we carried out an overview of the recent development of AMPs against K. pneumoniae using different designs and acting by different mechanisms, such as a recently proposed one against capsulated strains. Moreover, we outline AMPs' therapeutic potential when tested in combination with conventional antibiotics and against biofilms. Furthermore, challenges and perspectives for applying AMPs in clinical practice are discussed here.

Deciphering bioactive peptides and their action mechanisms through proteomics.

INTRODUCTION: Bioactive peptides such as antimicrobial peptides (AMPs), ribosomally synthesized and post translationally modified peptides (RiPPs) and the non-ribosomal peptides (NRPs) have emerged with promising applications in medicine, agriculture and industry. However, their development has been limited by several difficulties making it necessary to search for novel discovery methods. In this context, proteomics has been considered a reliable tool. Areas covered: This review highlights recent developments in proteomic tools that facilitate the discovery of AMPs, RiPPs and NRPs as well as the elucidation of action mechanisms of AMPs and resistance mechanisms of pathogens to them. Expert commentary: Proteomic approaches have emerged as useful tools for the study of bioactive peptides, especially mass spectrometry-based peptidomics profiling, a promising strategy for AMP discovery. Furthermore, the rapidly expanding fields of genome mining and genome sequencing techniques, as well as mass spectrometry, have revolutionized the discovery of novel RiPPs and NRPs from complex biological samples.