Fatin Siti N, Boon-Khai Tan, Shu-Chien Alexander Chong, Khairuddean Melati, Al-Ashraf Abdullah Amirul
Centre for Chemical Biology, Universiti Sains Malaysia, Bayan Lepas, Malaysia.
Malaysian Institute of Pharmaceuticals and Nutraceuticals (IPHARM), National Institute of Biotechnology Malaysia, Ministry of Science, Technology and Innovation, Bukit Gambir, Malaysia.
Front Microbiol. 2017 Nov 16;8:2267. doi: 10.3389/fmicb.2017.02267. eCollection 2017.
The resistance of to conventional antimicrobial treatment is a major scourge in healthcare. Therefore, it is crucial that novel potent anti-infectives are discovered. The aim of the present study is to screen marine actinomycetes for chemical entities capable of overcoming infection through mechanisms involving anti-virulence or host immunity activities. A total of 18 actinomycetes isolates were sampled from marine sediment of Songsong Island, Kedah, Malaysia. Upon confirming that the methanolic crude extract of these isolates do not display direct bactericidal activities, they were tested for capacity to rescue infected with strain PA14. A hexane partition of the extract from one isolate, designated as sp. CCB-PSK207, could promote the survival of PA14 infected worms by more than 60%. Partial 16S sequence analysis on this isolate showed identity of 99.79% with . This partition did not impair feeding behavior of worms. Tested on PA14, the partition also did not affect bacterial growth or its ability to colonize host gut. The production of biofilm, protease, and pyocyanin in PA14 were uninterrupted, although there was an increase in elastase production. In ::GFP worms, this partition was shown to induce the expression of , an important innate immunity defense molecule that was repressed during PA14 infection. GC-MS analysis of the bioactive fraction of sp. CCB-PSK207 revealed the presence of methyl esters of branched saturated fatty acids. In conclusion, this is the first report of a marine actinomycete producing metabolites capable of rescuing from PA14 through a mediated activity.
对传统抗菌治疗产生耐药性是医疗保健领域的一大祸害。因此，发现新型强效抗感染药物至关重要。本研究的目的是筛选海洋放线菌，寻找能够通过涉及抗毒力或宿主免疫活性的机制克服感染的化学物质。总共从马来西亚吉打州松松岛的海洋沉积物中采集了18株放线菌分离株。在确认这些分离株的甲醇粗提物不显示直接杀菌活性后，测试它们拯救被PA14菌株感染的秀丽隐杆线虫的能力。来自一株被命名为链霉菌属CCB-PSK207的分离株提取物的己烷馏分，可使被PA14感染的线虫存活率提高60%以上。对该分离株进行的部分16S序列分析显示，其与[具体菌株名称未给出]的同一性为99.79%。该馏分不损害秀丽隐杆线虫的摄食行为。在PA14上进行测试时，该馏分也不影响细菌生长或其在宿主肠道内定殖的能力。PA14中生物膜、蛋白酶和绿脓菌素的产生未受影响，尽管弹性蛋白酶的产生有所增加。在转入绿色荧光蛋白（GFP）的秀丽隐杆线虫中，该馏分可诱导[具体基因名称未给出]的表达，该基因是一种重要的固有免疫防御分子，在PA14感染期间受到抑制。对链霉菌属CCB-PSK207的生物活性部分进行气相色谱-质谱（GC-MS）分析，发现存在支链饱和脂肪酸的甲酯。总之，这是关于一种海洋放线菌产生能够通过[具体分子名称未给出]介导的活性从PA14感染中拯救秀丽隐杆线虫的代谢产物的首次报道。
