Polyamines are ubiquitous polycationic molecules that are present in all prokaryotic and eukaryotic cells, and they serve as important modulators of cell growth, stress, and cell proliferation. Polyamines are present at high concentrations in the periodontal pocket and could potentially affect the stress response of periodontal bacteria to antibiotics. The effects of polyamines on inhibition of growth by amoxicillin (AMX), azithromycin (AZM), and doxycycline (DOX) were investigated with the Y4 strain of Aggregatibacter actinomycetemcomitans (Aa). Bacteria were grown in brain heart infusion broth under the following conditions: (1) Aa only, (2) Aa + polyamine mix (1 mM putrescine, 0.4 mM spermidine, and 0.4 mM spermine), (3) Aa + antibiotic, and (4) Aa + antibiotic + polyamines. Growth curve analysis, minimal inhibitory concentration determination, and transcriptomic studies were conducted. The presence of exogenous polyamines produced a small, but significant increase in Aa growth, and polyamines attenuated the inhibitory effects of AMX, AZM, and DOX on growth. Transcriptomic analysis revealed that polyamines upregulate expression of ribosomal biogenesis proteins and small subunits, attenuate the bacterial stress response to antibiotics, and modulate bacterial nutritional pathways in a manner that could potentially increase the virulence of Aa. In summary, the polyamine-rich environment found in periodontal pockets appears to protect Aa and reduce its susceptibility to several antimicrobial agents in this in vitro model.

中文翻译：

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多胺对伴随放线菌 Y4 抗生素抑制生长的衰减研究的体外模型

多胺是普遍存在的聚阳离子分子，存在于所有原核和真核细胞中，它们是细胞生长、应激和细胞增殖的重要调节剂。多胺以高浓度存在于牙周袋中，可能会影响牙周细菌对抗生素的应激反应。研究了多胺对阿莫西林 (AMX)、阿奇霉素 (AZM) 和多西环素 (DOX) 抑制生长的作用，并用放线聚合杆菌( Aa ) 的 Y4 菌株进行了研究。细菌在以下条件下在脑心浸液肉汤中生长：(1)仅Aa，(2) Aa + 多胺混合物（1 mM 腐胺、0.4 mM 亚精胺和 0.4 mM 精胺），(3)Aa + 抗生素，和 (4) Aa + 抗生素 + 多胺。进行了生长曲线分析、最小抑制浓度测定和转录组学研究。外源多胺的存在对Aa生长产生了少量但显着的增加，并且多胺减弱了 AMX、AZM 和 DOX 对生长的抑制作用。转录组学分析表明，多胺上调核糖体生物发生蛋白和小亚基的表达，减弱细菌对抗生素的应激反应，并以可能增加Aa毒力的方式调节细菌营养途径。总之，牙周袋中富含多胺的环境似乎可以保护Aa并在该体外模型中降低其对几种抗菌剂的敏感性。