(582y) Characterization of AmiBA2446, a Novel Bacteriolytic Enzyme Active Against Bacillus Species

Characterization of AmiBA2446, a novel bacteriolytic enzyme active against Bacillus species

As more bacterial pathogens become resistant to available antibiotics, there is a need to develop novel antibacterial agents [1]. A particularly relevant target of high economic and biodefense importance is the spore-forming pathogen Bacillus anthracis, the causative agent of anthrax. Given the high cost of decontamination and the recalcitrance of dormant spores [2] there is acute interest in developing an efficient and environmentally-friendly approach to decontamination. Bacteriophage endolysins and lytic enzymes encoded by bacterial genomes are emerging as promising antibacterial agents [3], with highly evolved specificity toward bacterium-specific peptidoglycan cell walls. Moreover, gained resistance against lytic enzymes appears to be extremely low compared to antibiotics, which represent a significant motivation for further investigation. In this work, we analyzed in silico the genome of Bacillus anthracis Str. Ames, and identified a novel lytic enzyme termed AmiBA2446, and demonstrated its bactericidal efficacy against B. anthracis and B. cereus. We observe that AmiBA2446 retains its activity in solution for at least 24 h at 50 °C, and at least 4 months at room temperature.  We also observed significant sporicidal activity in presence of environmental germinants. The approach used to identify and characterize AmiBA2446 showcases our ability to dramatically expand the repertoire of highly selective bactericidal agents. The environmentally-friendly nature and high stability of AmiBA2446 further expands its potential for commercial use. In fact, we are extending the approach used in this work for effective decontamination of other resistant bacterial pathogens by sequencing its genome and using bioinformatics to identify putative lytic enzymes. This approach, therefore, may be important for addressing the growing concern posed by antimicrobial resistance and could be very useful in surface decontamination strategies amongst others [4].

References

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2.        Driks, A., The dynamic spore. Proc Natl Acad Sci U S A, 2003. 100(6): p. 3007-9.

3.        Loessner, M.J., Bacteriophage endolysins--current state of research and applications. Curr Opin Microbiol, 2005. 8(4): p. 480-7.

4.        Pangule, R.C., et al., Antistaphylococcal nanocomposite films based on enzyme-nanotube conjugates. ACS Nano. 4(7): p. 3993-4000.