Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan 3004, Amsterdam, 1081 LA, The Netherlands.
Department of CBRN Protection, Netherlands Organization for Applied Scientific Research TNO, Rijswijk, 2288 GJ, The Netherlands.
Environ Microbiol Rep. 2022 Aug;14(4):570-576. doi: 10.1111/1758-2229.13069. Epub 2022 Apr 10.
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.
先前，我们发现了一种与 d-立体专一性蛋白酶（DSPs）相关的芽孢杆菌属特异性肽酶活性。该肽酶对 d-亮氨酸和 d-缬氨酸氨基酸表现出强烈的偏好。这些氨基酸存在于非核糖体肽（NRP）抗生素短杆菌肽 A、B 和 C 以及多粘菌素 E 的结构中。为了研究芽孢杆菌属 DSP 相关肽酶是否能水解这些 NRP，监测了氨基环醇 A 和 C 以及多粘菌素 E 对炭疽杆菌培养上清液中肽酶活性的影响。结果发现，两种短杆菌肽都以竞争性方式抑制了 DSP 相关活性。MALDI-TOF 分析显示，与炭疽杆菌培养上清液孵育后，短杆菌肽 A 的水解产物出现了。本研究表明，芽孢杆菌属特异性 DSP 样肽酶可能是细菌产生的，以获得对 NRP 抗生素的固有抗性。这些结果在研究抗菌药物耐药性方面非常重要，而将 DSP 相关活性转移到其他临床相关病原体可能对人类健康构成严重威胁。
