MMPphg from the thermophilic Meiothermus bacteriophage MMP17 as a potential antimicrobial agent against both Gram-negative and Gram-positive bacteria

Virol J. 2020 Aug 25;17(1):130. doi: 10.1186/s12985-020-01403-0.

Abstract

Background: New strategies are urgently needed to deal with the growing problem of multidrug-resistant bacterial pathogens. As the natural viruses against bacteria, recently, bacteriophages have received particular attention. Here, we identified and characterized a novel peptidoglycan hydrolase named MMPphg by decoding the complete genome sequence of Meiothermus bacteriophage MMP17, which was isolated in Tengchong hot spring in China and contains a circular genome of 33,172 bp in size and a GC content of 63.4%.

Findings: We cloned the MMPphg gene, overproduced and purified the phage lytic protein, which contains a highly conserved M23 metallopeptidase domain and can be activated by Mg2+ and Zn2+. MMPphg is capable of withstanding temperatures up to 70 °C, and preserved more than 80% of its activity after a 30 min treatment between 35 and 65 °C. More interestingly, by disrupting bacterial cells, MMPphg exhibits surprising antimicrobial activity against both Gram-negative and Gram-positive pathogenic bacteria, especially antibiotic-resistant strains such as Escherichia coli O157, Staphylococcus aureus and Klebsiella pneumonia.

Conclusions: In the current age of mounting antibiotic resistance, these results suggest the great potential of MMPphg, the gene product of bacteriophage MMP17, in combating bacterial infections and shed light on bacteriophage-based strategies to develop alternatives to conventional antibiotics for human or veterinary applications.

Keywords: Antibiotic-resistant bacteria; Antimicrobial activity; Endolysin; Genome sequencing; Meiothermus bacteriophage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / pharmacology*
  • Bacteriophages / enzymology*
  • Bacteriophages / genetics
  • China
  • DNA, Viral / genetics
  • Drug Resistance, Bacterial
  • Enzyme Stability
  • Gram-Negative Bacteria / drug effects*
  • Gram-Positive Bacteria / drug effects*
  • Hot Temperature
  • Metalloproteases / metabolism
  • N-Acetylmuramoyl-L-alanine Amidase / isolation & purification
  • N-Acetylmuramoyl-L-alanine Amidase / pharmacology*
  • Whole Genome Sequencing

Substances

  • Anti-Infective Agents
  • DNA, Viral
  • Metalloproteases
  • N-Acetylmuramoyl-L-alanine Amidase