Lysins as a powerful alternative to combat Bacillus anthracis

Abstract

This review gathers all, to the best of our current knowledge, known lysins, mainly bacteriophage-derived, that have demonstrated activity against Bacillus anthracis strains. B. anthracis is a spore-forming, toxin-producing bacteria, naturally dwelling in soil. It is best known as a potential biowarfare threat, an etiological agent of anthrax, and a severe zoonotic disease. Anthrax can be treated with antibiotics (ciprofloxacin, penicillin, doxycycline); however, their administration may take up even to 60 days, and different factors can compromise their effectiveness. Bacterial viruses, bacteriophages (phages), are natural enemies of bacteria and use their lytic enzymes, endolysins (lysins), to specifically kill bacterial cells. Harnessing the potential of lysins to combat bacterial infections holds promise for diminishing antibiotic usage and, consequently, addressing the escalating antibiotic resistance in bacteria. In this context, we list the lysins with the activity against B. anthracis, providing a summary of their lytic properties in vitro and the outcomes observed in animal models. Bacillus cereus strain ATCC 4342/RSVF1, a surrogate for B. anthracis, was also included as a target bacteria. KEY POINTS: • More than a dozen different B. anthracis lysins have been identified and studied. • They fall into three blocks regarding their amino acid sequence similarity and most of them are amidases. • Lysins could be used in treating B. anthracis infections.

Keywords: Bacillus anthracis; Anthrax; CBD domain; Endolysin; Lytic activity.

Fig. 1

Multiple sequence alignment of the cell wall–binding domains of the 17 B. anthracis lysins. The alignment and the positioning of the particular domains were generated by ClustalW. Three distinct blocks, indicated by red frames, were proposed to encompass the most similar CBDs sharing analogous domain types, spanning from Block I at the top to Block III at the bottom of the alignment. Within each block, amino acid residues common to more than half of the aligned sequences are highlighted in blue, green, and pink. Yellow indicates the amino acid residues that are conserved across more than one block. Purple indicates the amino acid residues critical for the binding activity of PlyG to B. anthracis (Kikkawa 2007), which are repeated in the closely related lysins within the respective block. The sequences of the short linkers connecting two CBDs in lysins Ply57, gp217, LysPW2, and LysBC17 are marked by green frames

Fig. 2

Phylogenetic tree of CBD domains. The amino acid sequence of each CBD domain was used to create a neighbor-joining tree without distance corrections (UniProt). Blue represents Cluster 1, green Cluster 2, and pink Cluster 3 of the CBDs domain