摘要
      尽管防腐剂在牙科诊所和口腔护理产品中广泛使用，但公众很少意识到与防腐剂耐药性和潜在的交叉耐药性相关的潜在风险。因此，本研究的目的是研究177个牙菌斑早期定植菌（链球菌、放线菌、Rothia和Veillonella spp.）的临床分离株在使用改良的微量稀释方法重复暴露于低于抑制浓度的氯己定二葡糖酸盐（CHX）或氯化十六烷基吡啶鎓（CPC）10代后的潜在表型适应。在不含防腐剂的营养肉汤中培养24或72小时后，重新评估表型适应的稳定性。对表现出8倍最小抑制浓度（MIC）增加的菌株进一步检查其生物膜形成能力、表型抗生素抗性和抗生素抗性基因（ARGs）的存在。在四个链球菌分离株中检测到对CHX的MIC增加了八倍。与它们各自的野生型菌株相比，这些菌株大多表现出显著增加的生物膜形成能力。检测到对四环素和红霉素的表型抗生素耐药性，与检测到的ARGs一致。总之，这项研究表明，牙菌斑早期定植物的临床分离株在反复暴露后可以表型上适应防腐剂，如CHX。基因组和转录组水平的潜在机制需要在未来的研究中进行研究。
Abstract
Despite the wide-spread use of antiseptics in dental practice and oral care products, there is little public awareness of potential risks associated with antiseptic resistance and potentially concomitant cross-resistance. Therefore, the aim of this study was to investigate potential phenotypic adaptation in 177 clinical isolates of early colonizers of dental plaque (Streptococcus, Actinomyces, Rothia and Veillonella spp.) upon repeated exposure to subinhibitory concentrations of chlorhexidine digluconate (CHX) or cetylpyridinium chloride (CPC) over 10 passages using a modified microdilution method. Stability of phenotypic adaptation was re-evaluated after culture in antiseptic-free nutrient broth for 24 or 72 h. Strains showing 8-fold minimal inhibitory concentration (MIC)-increase were further examined regarding their biofilm formation capacity, phenotypic antibiotic resistance and presence of antibiotic resistance genes (ARGs). Eight-fold MIC-increases to CHX were detected in four Streptococcus isolates. These strains mostly exhibited significantly increased biofilm formation capacity compared to their respective wild-type strains. Phenotypic antibiotic resistance was detected to tetracycline and erythromycin, consistent with the detected ARGs. In conclusion, this study shows that clinical isolates of early colonizers of dental plaque can phenotypically adapt toward antiseptics such as CHX upon repeated exposure. The underlying mechanisms at genomic and transcriptomic levels need to be investigated in future studies.

https://www.mdpi.com/2079-6382/11/5/688