Strategies and molecular tools to fight antimicrobial resistance: resistome, transcriptome, and antimicrobial peptides

Abstract

The increasing number of antibiotic resistant bacteria motivates prospective research toward discovery of new antimicrobial active substances. There are, however, controversies concerning the cost-effectiveness of such research with regards to the description of new substances with novel cellular interactions, or description of new uses of existing substances to overcome resistance. Although examination of bacteria isolated from remote locations with limited exposure to humans has revealed an absence of antibiotic resistance genes, it is accepted that these genes were both abundant and diverse in ancient living organisms, as detected in DNA recovered from Pleistocene deposits (30,000 years ago). Indeed, even before the first clinical use of antibiotics more than 60 years ago, resistant organisms had been isolated. Bacteria can exhibit different strategies for resistance against antibiotics. New genetic information may lead to the modification of protein structure affecting the antibiotic carriage into the cell, enzymatic inactivation of drugs, or even modification of cellular structure interfering in the drug-bacteria interaction. There are still plenty of new genes out there in the environment that can be appropriated by putative pathogenic bacteria to resist antimicrobial agents. On the other hand, there are several natural compounds with antibiotic activity that may be used to oppose them. Antimicrobial peptides (AMPs) are molecules which are wide-spread in all forms of life, from multi-cellular organisms to bacterial cells used to interfere with microbial growth. Several AMPs have been shown to be effective against multi-drug resistant bacteria and have low propensity to resistance development, probably due to their unique mode of action, different from well-known antimicrobial drugs. These substances may interact in different ways with bacterial cell membrane, protein synthesis, protein modulation, and protein folding. The analysis of bacterial transcriptome may contribute to the understanding of microbial strategies under different environmental stresses and allows the understanding of their interaction with novel AMPs.

Keywords: NGS applications; antimicrobial peptides; genetic; molecular modeling; resistome; transcription.

Figure 1

Schematic antimicrobial peptides prospecting from the in silico analysis of sequences obtained by next generation sequencing. The demand for new antimicrobials to prevent microbial resistance from multifunctional action encourages the search for AMPs through prediction for next-generation sequencing followed by analysis of bioinformatics and computational modeling in order to produce effective peptides after antimicrobial trials. PDB IDs 3GP6; 1THQ; 2JSO; 3HUM; 2L24; 2KUS; 2LB7; 2NY8.