Kavya Boyina, King Blake, Rigsbee Abby S, Yang Jennifer G, Sprinkles Wilson, Patel Visha M, McDonald Allison A, Amburn Sue Katz, Champlin Franklin R
Department of Biochemistry and Molecular Biology, College of Agriculture, Oklahoma State University, Stillwater, OK, USA.
Department of Natural Sciences, College of Science and Health Professions, Northeastern State University, Broken Arrow, OK, USA.
Heliyon. 2023 Apr 8;9(4):e15385. doi: 10.1016/j.heliyon.2023.e15385. eCollection 2023 Apr.
Triclosan is a hydrophobic antimicrobial agent commonly employed in health care settings. While it exhibits broad-spectrum antibacterial properties, the gram-negative nosocomial opportunists and are atypically refractory. Intrinsic resistance to triclosan in is largely due to its outer membrane impermeability properties for hydrophobic and bulky substances. The present study was undertaken to determine the relationship between triclosan and the outer cell envelopes of thirteen strains of ten species reported to be opportunistic pathogens in humans. General intrinsic resistance to hydrophobic and other outer membrane impermeant compounds was assessed using cultural selection, disk agar diffusion, and macrobroth dilution bioassays. Uptake of the hydrophobic fluorescent probe 1--phenylnapthylamine was assessed in four disparate strains of . Batch culture kinetics in the presence of combinations of triclosan and outer membrane permeabilizer compound 48/80 allowed analysis of outer membrane involvement in intrinsic resistance. Aggregate results revealed that individual species ranged in response to hydrophobic and bulky molecules from generally refractory to extremely susceptible. Moreover, susceptivity to triclosan sensitization by chemical disruption of outer membrane exclusionary properties differed markedly among species which exhibited intrinsic resistance to triclosan. These data suggest that disparate opportunistic pathogens within the genus differ phenotypically regarding the degree to which outer membrane exclusion contributes to intrinsic resistance for impermeant molecules in general, and triclosan specifically. Ancillary resistance mechanisms appear to contribute in some species and may involve constitutive multi-drug efflux systems. A paucity of knowledge exists regarding the cellular and molecular mechanisms by which opportunistically pathogenic members of the genus are able to infect immunocompromised and otherwise susceptible individuals, and then evade chemotherapy. This is especially true for species other than and , although much remains to be learned with regard to the nature of key virulence factors and infection mechanisms which allow for the typically nosocomial acquisition of even these species. The research described in the present study will provide a better understanding of the contribution of outer cell envelope permeability properties to the pathogenicity of these opportunistic species in an ever-increasing susceptible patient population. It is our hope that greater knowledge of the basic biology of these organisms will contribute to the mitigation of suffering they cause in patients with underlying diseases.
三氯生是一种疏水性抗菌剂，常用于医疗保健环境。虽然它具有广谱抗菌特性，但革兰氏阴性医院机会致病菌对其具有非典型的耐药性。三氯生内在耐药性的产生主要是由于其外膜对疏水性和大分子物质的不渗透性。本研究旨在确定三氯生与13株属于10个物种的菌株外细胞膜之间的关系，这些菌株被报道为人类机会致病菌。通过培养选择、纸片琼脂扩散和大管肉汤稀释生物测定法评估了对疏水性和其他外膜不透性化合物的一般内在耐药性。在4株不同的菌株中评估了疏水性荧光探针1-苯基萘胺的摄取。在三氯生和外膜通透剂化合物48/80组合存在的情况下进行分批培养动力学分析，以分析外膜在内在耐药性中的作用。综合结果显示，不同物种对疏水性和大分子物质的反应各不相同，从一般耐药到极度敏感。此外，在对三氯生具有内在耐药性的物种中，通过化学破坏外膜排斥特性对三氯生致敏的敏感性差异显著。这些数据表明，该属内不同的机会致病菌在外膜排斥对一般不透性分子特别是三氯生内在耐药性的贡献程度方面存在表型差异。辅助耐药机制似乎在某些物种中起作用，可能涉及组成型多药外排系统。关于该属机会致病菌能够感染免疫受损及其他易感个体，然后逃避化疗的细胞和分子机制，我们知之甚少。对于除[具体物种1]和[具体物种2]之外的物种尤其如此，尽管关于关键毒力因子的性质和感染机制仍有许多需要了解的地方，这些机制使得即使是这些物种也通常在医院获得感染。本研究中描述的研究将有助于更好地理解外细胞膜通透性特性对这些机会致病菌在不断增加的易感患者群体中致病性的贡献。我们希望对这些生物体基本生物学的更多了解将有助于减轻它们给患有基础疾病的患者带来的痛苦。
