A new genetic approach can accelerate the study of phage-microbe interactions with implications for health, agriculture, and climate
一種能加速有關噬菌體與微生物交互作用之研究新的遺傳方法，對健康、農業及氣候具有諸多意涵。
圖1. 這張經著色的透射式電子顯微照片顯示了，大量噬菌體附著在細菌細胞壁上。 (圖援用自原文)
Scientists are continually searching for new and improved ways to deal with bacteria, be it to eliminate disease-causing strains or to modify potentially beneficial strains. And despite the numerous clever drugs and genetic engineering tools humans have invented for these tasks, those approaches can seem clumsy when compared to the finely tuned attacks waged by phages – the viruses that infect bacteria.
科學家們正持續找尋應付細菌，經改善的新方法來處理細菌。也就是，剔除致病菌株，或修飾潛在有益的菌株。不過，儘管人類為此些工作，已經發明諸多令人滿意的藥物及遺傳工程工具。當與噬菌體進行的攻擊作比較時，那些方法看來應是笨拙的。
Phages, like other parasites, are continually evolving ways to target and exploit their specific host bacterial strain, and in turn, the bacteria are continually evolving means to evade the phages. These perpetual battles for survival yield incredibly diverse molecular arsenals that researchers are itching to study, yet doing so can be tedious and labor-intensive.
與其他寄生蟲一樣，噬菌體也正持續演化諸多方式，來鎖定及利用其特定宿主細菌的菌株。依序，細菌也持續演化諸多方法，來規避噬菌體。此些為生存的持久戰，令人難以置信地產生了，研究人員們渴望進行研究，不過這麼做會是冗長乏味，且勞動密集的多種分子武器庫。
To gain insight into these defensive strategies, a team led by Berkeley Lab scientists has just developed an efficient and inexpensive new method. As reported in PLOS Biology, the team showed that a combination of three techniques can reveal which bacterial receptors phages exploit to infect the cell, as well as what cellular mechanisms the bacteria use to respond to a phage infection.
為了獲得此些防禦策略的洞察力，一支由美國柏克萊實驗室，科學家們領導的團隊已經剛研發出一種，有效率且廉價的新方法。如同於《公共科學圖書館：生物學》期刊中記述的，該團隊證實，結合三種技術，除了細菌使用什麽細胞機制，來對噬菌體感染作出反應之外，也能揭露噬菌體利用哪些細菌受體，來感染細胞。
“Despite nearly a century of molecular work, the underlying mechanisms of phage-host interactions are only known for a few pairs, where the host is a well-studied model organism that can be cultured in a lab,” said corresponding author Vivek Mutalik, a research scientist in Berkeley Lab’s Environmental Genomics and Systems Biology (EGSB) Division.
通訊撰文人，柏克萊實驗室環境基因體學暨系統生物學(EGSB)部門的研究科學家，Vivek Mutalik宣稱：「儘管將近一個世紀的分子研究，不過有關噬菌體與宿主之交互作用的潛在機制，已知僅有幾對。在宿主方面是能在實驗室中，被培養、經充分研究的模型生物。」
However, phages represent the most abundant biological entities on Earth, and due to their impact on bacteria, they are key drivers of environmental nutrient cycles, agricultural output, and human and animal health. It has become imperative to gain more foundational knowledge of these interactions in order to better understand the planet’s microbiomes and to develop new medicines, such as bacteria-based vaccines or phage cocktails to treat antibiotic-resistant infections.”
不過，噬菌體是地球上最豐富的生物實體，由於它們對細菌的影響，它們是環境養分循環、農業產量及人類與動物健康的關鍵驅動物。為了更深入瞭解地球的微生物群落，及開發諸如以細菌為基礎的疫苗，或噬菌體雞尾酒，來治療對抗生素具抵抗力之感染的新藥物。」
The team’s three-pronged approach, called barcoded loss-of-function and gain-of-function libraries, uses the established technique of creating gene deletions and also increasing gene expression to identify which genes the bacteria use to evade the phages.
該團隊被稱為條碼功能喪失及功能增益庫之三管齊下的方法，使用了經證實產生基因缺失且也提升基因表現，以確認細菌使用哪些基因，來規避噬菌體的技術。
This information also tells the scientists which receptors the phages are targeting without having to analyze the phages’ genomes. (However, the scientists do plan to adapt the technique for use on viruses in the future, to learn even more about their function.)
無需分析噬菌體的基因體，這種訊息也能告訴科學家們，噬菌體正鎖定哪些受體。(不過，為了於未來使用於病毒上，科學家們確實計劃，修改該項技術。)
Mutalik and his colleagues tested their method on two strains of E. coli that are known to be targeted by 14 genetically diverse phages. Their results confirmed that the method works smoothly by speedily revealing the same suite of phage receptors that had been previously identified through decades of research, and also provided new hits that were missed in earlier studies.
Mutalik及其同僚們針對，已知遭14種遺傳上不同之噬菌體鎖定的兩種大腸桿菌菌株，試驗了他們的方法。因快速揭露經過數十年研究，先前已經被確認的同組噬菌體受體。他們的試驗結果證實，該種方法平順地運作。因此，也提供了早期諸多研究中，遭漏掉的新事物。
According to Mutalik, the approach can also be scaled-up to simultaneously evaluate phage relationships for hundreds of bacteria sampled from diverse environments.
根據Mutalik的說法，此方法也能被擴大規模來同時評估，採自不同環境之數百種細菌的噬菌體關係。
This will make it much easier for scientists to study the planet’s biological “dark matter,” which refers to the unculturable and therefore poorly understood microorganisms that abound in many environments. In fact, it is estimated that 99% of all living microorganisms can’t be cultured in a lab.
對科學家們而言，這將使其更容易研究地球，大量存在於諸多環境中，適用於無法培養，因此鮮少被瞭解的微生物“暗物質”。實際上，據估所有的活微生物，在實驗室中，99％無法被培養。
The team’s approach also represents an opportunity to standardize genetic resources used in phage research, which has always been an ad-hoc and highly variable process, and create sharable reagents and datasets.
該團隊的方法也代表了，標準化被使用於噬菌體研究中之遺傳資源的一個機會。這始終是一種特別且高度可變的方法，因此創建了可共享的反應物(試劑)及數據集。
“The role of phages is a huge ‘known-unknown,’ as we know there are phages everywhere, but hardly know anything more. For example, we understand less than 10% of the genes encoded in previously sequenced phage genomes,” said Mutalik. “Now that we finally have a streamlined tool to look at phages, there are many exciting questions we can start to answer and an opportunity to make a difference in the world.”
Mutalik宣稱：「噬菌體的角色是一大“已知的未知事”。因為他們知曉到處有噬菌體，不過幾乎一無所知。譬如，在先前經排序之噬菌體之基因體中，被編碼的基因，他們瞭解不到10％。由於終究擁有一種探究噬菌體的有效率工具，他們能開始回答諸多引人好奇的問題，及改變世界的機會。」
原文網址：https://newscenter.lbl.gov/2020/12/10/phages-natures-hidden-arsenal/
翻譯：許東榮
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