Fighting against evolution of antibiotic resistance by utilizing evolvable antimicrobial drugs

Curr Genet. 2017 Dec;63(6):973-976. doi: 10.1007/s00294-017-0703-x. Epub 2017 May 11.

Abstract

Antibiotic resistance is a worldwide public health problem (Bush et al. in Nat Rev Microbiol 9:894-896, 2011). The lack of effective therapies against resistant bacteria globally leads to prolonged treatments, increased mortality, and inflating health care costs (Oz et al. in Mol Biol Evol 31:2387-2401, 2014; Martinez in Science 321:365-367, 2008; Lipsitch et al. in Proc Natl Acad Sci USA 97:1938-1943, 2000; Taubes in Science 321:356-361, 2008; Laxminarayan et al. in Lancet, 2016; Laxminarayan et al. in Lancet Infect Dis 13:1057-1098, 2013). Current efforts towards a solution of this problem can be boiled down to two main strategies: (1) developing of new antimicrobial agents and (2) searching for smart strategies that can restore or preserve the efficacy of existing antimicrobial agents. In this short review article, we discuss the need for evolvable antimicrobial agents, focusing on a new antimicrobial technology that utilizes peptide-conjugated phosphorodiamidate morpholino oligomers to inhibit the growth of pathogenic bacteria by targeting bacterial genes.

Keywords: Antibiotic resistance; Evolution; Gene silencing; Microbial evolution; Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs).

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / pharmacology*
  • Drug Resistance, Microbial / drug effects*
  • Drug Resistance, Microbial / genetics
  • Escherichia coli / drug effects
  • Escherichia coli / genetics
  • Escherichia coli / growth & development
  • Escherichia coli Proteins / antagonists & inhibitors*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Evolution, Molecular
  • Gene Expression Regulation, Bacterial*
  • Gene Silencing
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / genetics
  • Klebsiella pneumoniae / growth & development
  • Lipoproteins / antagonists & inhibitors*
  • Lipoproteins / genetics
  • Lipoproteins / metabolism
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Microbial Sensitivity Tests
  • Morpholinos / chemical synthesis
  • Morpholinos / pharmacology*
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Salmonella enterica / drug effects
  • Salmonella enterica / genetics
  • Salmonella enterica / growth & development

Substances

  • AcrA protein, E coli
  • Anti-Bacterial Agents
  • Escherichia coli Proteins
  • Lipoproteins
  • Membrane Transport Proteins
  • Morpholinos
  • Peptides