Srivastava A, Singh B N, Deepak D, Rawat A K S, Singh B R
Pharmacognosy & Ethnopharmacology Division, CSIR-National Botanical Research Institute, Lucknow, Uttar Pradesh, India Chemistry Department, Lucknow University, Lucknow, Uttar Pradesh, India.
Pharmacognosy & Ethnopharmacology Division, CSIR-National Botanical Research Institute, Lucknow, Uttar Pradesh, India
Antimicrob Agents Chemother. 2015 Apr;59(4):2169-78. doi: 10.1128/AAC.03722-14. Epub 2015 Feb 2.
The discovery of quorum-sensing (QS) systems regulating antibiotic resistance and virulence factors (VFs) has afforded a novel opportunity to prevent bacterial pathogenicity. Dietary molecules have been demonstrated to attenuate QS circuits of bacteria. But, to our knowledge, no study exploring the potential of colostrum hexasaccharide (CHS) in regulating QS systems has been published. In this study, we analyzed CHS for inhibiting QS signaling in Staphylococcus aureus. We isolated and characterized CHS from mare colostrum by high-performance thin-layer chromatography (HPTLC), reverse-phase high-performance liquid chromatography evaporative light-scattering detection (RP-HPLC-ELSD), (1)H and (13)C nuclear magnetic resonance (NMR), and electrospray ionization mass spectrometry (ESI-MS). Antibiofilm activity of CHS against S. aureus and its possible interference with bacterial QS systems were determined. The inhibition and eradication potentials of the biofilms were studied by microscopic analyses and quantified by 96-well-microtiter-plate assays. Also, the ability of CHS to interfere in bacterial QS by degrading acyl-homoserine lactones (AHLs), one of the most studied signal molecules for Gram-negative bacteria, was evaluated. The results revealed that CHS exhibited promising inhibitory activities against QS-regulated secretion of VFs, including spreading ability, hemolysis, protease, and lipase activities, when applied at a rate of 5 mg/ml. The results of biofilm experiments indicated that CHS is a strong inhibitor of biofilm formation and also has the ability to eradicate it. The potential of CHS to interfere with bacterial QS systems was also examined by degradation of AHLs. Furthermore, it was documented that CHS decreased antibiotic resistance in S. aureus. The results thus give a lead that mare colostrum can be a promising source for isolating a next-generation antibacterial.
群体感应(QS)系统可调控抗生素耐药性和毒力因子(VF),这一发现为预防细菌致病性提供了新契机。膳食分子已被证明可减弱细菌的群体感应回路。但据我们所知,尚未有研究探讨初乳六糖(CHS)在调控群体感应系统方面的潜力。在本研究中,我们分析了CHS对金黄色葡萄球菌群体感应信号的抑制作用。我们通过高效薄层色谱法(HPTLC)、反相高效液相色谱蒸发光散射检测法(RP-HPLC-ELSD)、(1)H和(13)C核磁共振(NMR)以及电喷雾电离质谱法(ESI-MS)从马初乳中分离并鉴定了CHS。测定了CHS对金黄色葡萄球菌的抗生物膜活性及其对细菌群体感应系统的可能干扰。通过显微镜分析研究了生物膜的抑制和根除潜力,并通过96孔微量滴定板试验进行定量。此外,还评估了CHS通过降解酰基高丝氨酸内酯(AHLs)来干扰细菌群体感应的能力,AHLs是革兰氏阴性菌研究最多的信号分子之一。结果显示,当以5mg/ml的浓度应用时,CHS对群体感应调节的毒力因子分泌表现出有前景的抑制活性,包括扩散能力、溶血、蛋白酶和脂肪酶活性。生物膜实验结果表明,CHS是生物膜形成的强力抑制剂,且有能力根除生物膜。还通过AHLs的降解研究了CHS干扰细菌群体感应系统的潜力。此外,有文献记载CHS可降低金黄色葡萄球菌的抗生素耐药性。因此,这些结果表明马初乳可能是分离下一代抗菌剂的有前景来源。