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Updated: Sep 27, 2025

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Published on: January 7, 2022
Gramicidin A is hydrolyzed by a d-stereospecific peptidase produced by Bacillus anthracis
Wendy E Kaman1, Kamran Nazmi1, A Ingrid Voskamp-Visser2
1Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan 3004, Amsterdam, 1081 LA, The Netherlands.
Abstract:
Previously we described the discovery of a Bacillus spp. specific peptidase activity related to d-stereospecific peptidases (DSPs). The peptidase showed a strong preference for d-leucine and d-valine amino acids. These amino acids are present in the structure of the non-ribosomal peptide (NRP) antibiotics gramicidin A, B and C and polymyxin E. To examine if the Bacillus spp. DSP-related peptidase can hydrolyze these NRPs, the effect of gramicidin A and C and polymyxin E on peptidase activity in Bacillus anthracis culture supernatant was monitored. It was found that both gramicidins inhibited the DSP-related activity in a competitive manner. MALDI-TOF analysis revealed that upon incubation with B. anthracis culture supernatant gramicidin A hydrolyzation products appeared. This study shows that the Bacillus spp. specific DSP-like peptidase was potentially produced by the bacteria to gain intrinsic resistance against NRP antibiotics. These results are of utmost importance in research towards antimicrobial resistance, whereas transfer of DSP-related activity to other clinically relevant pathogens can be a serious threat to human health.
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