Scorpion Venom Antimicrobial Peptides Induce Siderophore Biosynthesis and Oxidative Stress Responses in Escherichia coli

Abstract

The increasing development of microbial resistance to classical antimicrobial agents has led to the search for novel antimicrobials. Antimicrobial peptides (AMPs) derived from scorpion and snake venoms offer an attractive source for the development of novel therapeutics. Smp24 (24 amino acids [aa]) and Smp43 (43 aa) are broad-spectrum AMPs that have been identified from the venom gland of the Egyptian scorpion Scorpio maurus palmatus and subsequently characterized. Using a DNA microarray approach, we examined the transcriptomic responses of Escherichia coli to subinhibitory concentrations of Smp24 and Smp43 peptides following 5 h of incubation. Seventy-two genes were downregulated by Smp24, and 79 genes were downregulated by Smp43. Of these genes, 14 genes were downregulated in common and were associated with bacterial respiration. Fifty-two genes were specifically upregulated by Smp24. These genes were predominantly related to cation transport, particularly iron transport. Three diverse genes were independently upregulated by Smp43. Strains with knockouts of differentially regulated genes were screened to assess the effect on susceptibility to Smp peptides. Ten mutants in the knockout library had increased levels of resistance to Smp24. These genes were predominantly associated with cation transport and binding. Two mutants increased resistance to Smp43. There was no cross-resistance in mutants resistant to Smp24 or Smp43. Five mutants showed increased susceptibility to Smp24, and seven mutants showed increased susceptibility to Smp43. Of these mutants, formate dehydrogenase knockout (fdnG) resulted in increased susceptibility to both peptides. While the electrostatic association between pore-forming AMPs and bacterial membranes followed by integration of the peptide into the membrane is the initial starting point, it is clear that there are numerous subsequent additional intracellular mechanisms that contribute to their overall antimicrobial effect. IMPORTANCE The development of life-threatening resistance of pathogenic bacteria to the antibiotics typically in use in hospitals and the community today has led to an urgent need to discover novel antimicrobial agents with different mechanisms of action. As an ancient host defense mechanism of the innate immune system, antimicrobial peptides (AMPs) are attractive candidates to fill that role. Scorpion venoms have proven to be a rich source of AMPs. Smp24 and Smp43 are new AMPs that have been identified from the venom gland of the Egyptian scorpion Scorpio maurus palmatus, and these peptides can kill a wide range of bacterial pathogens. By better understanding how these AMPs affect bacterial cells, we can modify their structure to make better drugs in the future.

Identification and Exploration of Transcripts Involved in Antibiotic Resistance Mechanism of Two Critical Superbugs

“…38 Hierarchical clustering was used to group the strain samples, and the dendrogram is displayed at the top of a heatmap that shows the Pearson correlation between each pair of samples. 39 Sample identity was shown by two-way color indexing the group and strain. The results demonstrated that KP and PA samples from different groups and strains could be successfully distinguished.…”

Antimicrobial Peptide Analogs From Scorpions: Modifications and Structure-Activity

“…Furthermore, some AMPs can target intracellular components such as nucleic acid and proteins. It has been reported that AMPs Smp24 and Smp43 from the Egyptian scorpion Scorpio maurus palmatus not only disrupt bacterial cell membranes but can also interfere with intracellular gene expression ( Tawfik et al, 2021 ). A study using radioactive isotopes clearly showed that I9K-IsCT and E7K, which are analogs of IsCT from the scorpion O. madagascariensis , inhibit nucleic acids and protein synthesis in E. coli ( Tripathi et al, 2015 ).…”

Antimicrobial Activity of Apis mellifera Bee Venom Collected in Northern Peru

“…One group of these new molecules are peptides that are antimicrobial (AMP) and are promising molecules for combating antimicrobial resistance (AMR) [ 28 ]. AMP has been found the most in the venoms of different organisms, such as scorpions [ 29 , 30 , 31 ], snakes [ 32 ], spiders [ 33 ], and bees [ 34 ], among other venoms.…”