Sulaiman Rand, Trizna Elena, Kolesnikova Alena, Khabibrakhmanova Alsu, Kurbangalieva Almira, Bogachev Mikhail, Kayumov Airat
Laboratory of Molecular Genetics of Microorganisms, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
Biofunctional Chemistry Laboratory, Alexander Butlerov Institute of Chemistry, Kazan Federal University, 420008 Kazan, Russia.
Pathogens. 2022 Dec 23;12(1):26. doi: 10.3390/pathogens12010026.
and are human pathogens that are able to form mixed biofilms on the surface of mucous membranes, implants and catheters. In biofilms, these pathogens have increased resistance to antimicrobials, leading to extreme difficulties in the treatment of mixed infections. The growing frequency of mixed infections caused by and requires either the development of new antimicrobials or the proposal of alternative approaches to increase the efficiency of conventional ones. Here, we show the antimicrobial, biofilm-preventing and biofilm-eradicating activity of 2(5)-furanone derivative containing an -borneol fragment against mixed biofilms. Furanone is also capable of inhibiting the formation of monospecies and mixed biofilms by and . The minimal biofilm-prevention concentration (MBPC) of this compound was 8-16 μg/mL for and mono- and two-species biofilms. While the compound demonstrates slightly lower activity compared to conventional antimicrobials (gentamicin, amikacin, fluconazole, terbinafine and benzalkonium chloride), also increases the antimicrobial activity of fluconazole-gentamicin and benzalkonium chloride against mixed biofilms of , thus reducing MBPC of fluconazole-gentamicin by 4-16 times and benzalkonium chloride twofold. does not affect the transcription of the MDR1, CDR1 and CDR2 genes, thus suggesting a low risk of micromycete resistance to this compound. Altogether, combined use of antibiotics with a could be a promising option to reduce the concentration of fluconazole used in antiseptic compositions and reduce the toxic effect of benzalkonium chloride and gentamicin. This makes them an attractive starting point for the development of alternative antimicrobials for the treatment of skin infections caused by mixed biofilms.
[具体病原体名称1]和[具体病原体名称2]是人类病原体，能够在粘膜、植入物和导管表面形成混合生物膜。在生物膜中，这些病原体对抗菌药物的耐药性增强，导致混合感染的治疗极其困难。由[具体病原体名称1]和[具体病原体名称2]引起的混合感染频率不断增加，这就需要开发新的抗菌药物，或者提出替代方法来提高传统抗菌药物的效率。在此，我们展示了含有冰片片段的2(5)-呋喃酮衍生物对[具体病原体名称1]和[具体病原体名称2]混合生物膜的抗菌、预防生物膜形成和消除生物膜的活性。呋喃酮也能够抑制[具体病原体名称1]和[具体病原体名称2]的单物种生物膜和混合生物膜的形成。该化合物对[具体病原体名称1]和[具体病原体名称2]的单物种和双物种生物膜的最低生物膜预防浓度（MBPC）为8 - 16μg/mL。虽然该化合物与传统抗菌药物（庆大霉素、阿米卡星、氟康唑、特比萘芬和苯扎氯铵）相比活性略低，但它也能增强氟康唑 - 庆大霉素和苯扎氯铵对[具体病原体名称1]和[具体病原体名称2]混合生物膜的抗菌活性，从而使氟康唑 - 庆大霉素的MBPC降低4 - 16倍，苯扎氯铵的MBPC降低两倍。[该化合物名称]不影响MDR1、CDR1和CDR2基因的转录，因此表明微真菌对该化合物产生耐药性的风险较低。总之，将抗生素与[该化合物名称]联合使用可能是一个有前景的选择，可以降低用于防腐组合物中的氟康唑浓度，并降低苯扎氯铵和庆大霉素的毒性作用。这使其成为开发用于治疗由[具体病原体名称1]和[具体病原体名称2]混合生物膜引起的皮肤感染的替代抗菌药物的有吸引力的起点。
