具備抗生素抗藥性的微生物的出現時間可追溯至4億5000萬年前，遠遠早於恐龍時代

原文網址：http://www.geologypage.com/2017/05/antibiotic-resistant-microbes-date-back-450-million-years-ago-well-age-dinosaurs.html

具備抗生素抗藥性的微生物的出現時間可追溯至4億5000萬年前，遠遠早於恐龍時代

曾經活過大滅絕的這件事蹟，有助於解釋醫院超級細菌為何具有近乎堅不可摧的性質

根據麻州眼耳專科醫院、泛哈佛抗生素抗藥性計畫以及麻省理工學院-哈佛大學布洛德研究所的研究人員主持的新研究，醫院的主要「超級細菌」――腸球菌(enterococci)，其祖先的崛起年代可追溯至4億5000萬年前，大約是第一隻動物爬上陸地的時候(遠早於恐龍時代)。這些病原體演化出近乎堅不可摧的能力，而成為現代醫院內部抗生素抗藥性細菌感染的主要原因。在今日刊登於《細胞》(Cell)的研究中，作者闡明了它們的演化史。

抗生素抗藥性現已成為一項全球關注的重要公共衛生議題。某些經常被稱為「超級細菌」的微生物幾乎對所有的抗生素都有抗藥性。對醫院來說，它們特別擔憂這些細菌，因為未來可能有5%左右的住院病人得對抗他們在住院期間遭到的感染。在世界各地的研究人員迫切尋找問題的解決方法時，從抗生素抗藥性的起源和演化歷程著眼，有助於啟發他們的研究。

「藉由分析現今腸球菌的基因體和行為模式，我們可以把時鐘反轉至它們最初存在的時刻，並拼湊出這些生物是如何逐步變成它們今日的樣貌。」共同通訊作者，麻省理工學院-哈佛大學布洛德研究所細菌基因體小組的組長Ashlee M. Earl博士表示。「瞭解微生物居住的環境如何使它們獲得新的特性，有助於我們預測使用抗生素、抗菌洗手液、消毒劑和其他用來控制微生物擴散的產品時，微生物會如何對其產生適應力。」

研究人員拼湊出來的圖像從生命剛出現的時候開始。細菌大約誕生於40億年前，自此之後包括海洋在內，整個地球就充斥著它們的存在。海洋首度出現動物是在5億4200萬年前，稱作寒武紀大爆發的事件中。當動物出現在滿是細菌的海洋中，細菌便學會在動物的體內與身上生存。某些細菌會保護並服務動物，如同今日生存在我們腸道中的益菌一般；有些則生活在環境中，還有些會造成疾病。隨著動物在大約1億年後緩緩爬上陸地，牠們也將身上的細菌帶往陸地。

此篇《細胞》論文的研究作者發現，包括從未在醫院發現的種類在內，所有的腸球菌自然而然地就對乾旱、飢餓、消毒劑和許多種類的抗生素有抵抗力。由於大多數陸生動物的腸道中一般都有腸球菌在此生活，因此它們也很可能曾生活在現已滅絕的陸生動物的腸道裏，包括恐龍和首度爬上陸地，像蜈蚣般的生物在內。比較這些細菌的基因體呈現出的證據顯示確實如此。事實上，研究團隊發現每當新的動物類型出現時，就會產生新品種的腸球菌。包括了動物首次登陸，許多新型動物隨之產生的時候；以及大滅絕過後不久，許多新型動物趁勢崛起的時候，其中又以二疊紀結束時(2億5100萬年前)，史上最慘重的大滅絕為甚。

從魚之類的海洋生物體內，腸道微生物會被排泄到海水之中。海中每滴海水通常含有5000株大都無害的細菌。它們會沉到海底富含微生物的沉積物中，然後被蟲子、貝類和其他海中食腐動物吃掉。接著這些動物又會被魚類捕食，於是微生物便能經由食物鏈不斷循環。然而，在陸地腸道微生物會跟著排泄物一起排出，它們常常困在其中而逐漸喪失水分，大多數都會隨著時間過去而死亡。

但是，腸球菌卻不會如此。這些微生物通常十分堅韌，並且能夠忍受缺乏水份以及挨餓的狀況。此特性讓它們在陸地上，以及因為消毒劑的使用造成其他微生物難以生存的醫院中，都能生長得十分良好。

領導此研究的Michael S. Gilmore博士表示：「我們現在知道腸球菌在數億年前得到了什麼樣的基因，讓它們可以抵抗乾旱，以及抵禦會攻擊它們細胞壁的消毒劑和抗生素。」他是麻州眼耳專科醫院的高級研究員，以及哈佛傳染病研究所的主任。

此篇研究的第一作者，Gilmore團隊中的計畫主持人Francois Lebreton博士補充：「現在我們研究的目標，是要設計可以專門消滅腸球菌的新型抗生素和消毒劑，讓它們從住院患者的威脅名單上去除。」

這篇《細胞》論文的共同作者除了Earl、Gilmore和Lebreton博士之外，還包括了麻省理工學院-哈佛大學布洛德研究所的Abigail L. Manson博士和Timothy J. Straub，以及麻省理工學院的Jose T. Saavedra。

研究由美國衛生與人群服務部、美國國家衛生研究院、美國國家過敏與感染疾病研究所補助，計畫編號分別為AI072360、AI083214、HHSN272200900018C和U19AI110818

Antibiotic-resistant microbes date back to 450 million years ago, well before the age of dinosaurs

Survival of mass extinctions helps to explain near indestructible properties of hospital superbugs

Leading hospital “superbugs,” known as the enterococci, arose from an ancestor that dates back 450 million years — about the time when animals were first crawling onto land (and well before the age of dinosaurs), according to a new study led by researchers from Massachusetts Eye and Ear, the Harvard-wide Program on Antibiotic Resistance and the Broad Institute of MIT and Harvard. Published online today in Cell, the study authors shed light on the evolutionary history of these pathogens, which evolved nearly indestructible properties and have become leading causes of modern antibiotic-resistant infections in hospitals.

Antibiotic resistance is now a leading public health concern worldwide. Some microbes, often referred to as “superbugs,” are resistant to virtually all antibiotics. This is of special concern in hospitals, where about 5 percent of hospitalized patients will fight infections that arise during their stay. As researchers around the world are urgently seeking solutions for this problem, insight into the origin and evolution of antibiotic resistance will help inform their search.

“By analyzing the genomes and behaviors of today’s enterococci, we were able to rewind the clock back to their earliest existence and piece together a picture of how these organisms were shaped into what they are today” said co-corresponding author Ashlee M. Earl, Ph.D., group leader for the Bacterial Genomics Group at the Broad Institute of MIT and Harvard. “Understanding how the environment in which microbes live leads to new properties could help us to predict how microbes will adapt to the use of antibiotics, antimicrobial hand soaps, disinfectants and other products intended to control their spread.”

The picture the researchers pieced together begins with the dawn of life. Bacteria arose nearly 4 billion years ago, and the planet has teemed with them ever since, including the sea. Animals first arose in the sea during the time known as the Cambrian Explosion, 542 million years ago. As animals emerged in a sea of bacteria, bacteria learned to live in and on them. Some bacteria protect and serve the animals, as the healthy microbes in our intestines do today; others live in the environment, and still others cause disease. As animals crawled onto land about 100 million years later, they took their microbes with them.

The authors of the Cell study found that all species of enterococci, including those that have never been found in hospitals, were naturally resistant to dryness, starvation, disinfectants and many antibiotics. Because enterococci normally live in the intestines of most (if not all) land animals, it seemed likely that they were also in the intestines of land animals that are now extinct, including dinosaurs and the first millipede-like organisms to crawl onto land. Comparison of the genomes of these bacteria provided evidence that this was indeed the case. In fact, the research team found that new species of enterococci appeared whenever new types of animals appeared. This includes when new types of animals arose right after they first crawled onto land, and when new types of animals arose right after mass extinctions, especially the greatest mass extinction, the End Permian Extinction (251 million years ago).

From sea animals, like fish, intestinal microbes are excreted into the ocean, which usually contains about 5,000 mostly harmless bacteria per drop of water. They sink to the seafloor into microbe-rich sediments, and are consumed by worms, shellfish and other sea scavengers. Those are then eaten by fish, and the microbes continue to circulate throughout the food chain. However, on land, intestinal microbes are excreted as feces, where they often dry out and most die over time.

Not the enterococci, however. These microbes are unusually hardy and can withstand drying out and starvation, which serves them well on land and in hospitals where disinfectants make it difficult for a microbe.

“We now know what genes were gained by enterococci hundreds of millions of years ago, when they became resistant to drying out, and to disinfectants and antibiotics that attack their cell walls,” said study leader Michael S. Gilmore, Ph.D., senior scientist at Mass. Eye and Ear and Director of the Harvard Infectious Disease Institute.

“These are now targets for our research to design new types of antibiotics and disinfectants that specifically eliminate enterococci, to remove them as threats to hospitalized patients,” added Francois Lebreton, Ph.D., first author of the study and project leader for the Gilmore team.

In addition to Drs. Earl, Gilmore and Lebreton, authors on the Cell paper include Abigail L. Manson, Ph.D., and Timothy J. Straub, of the Broad Institue of MIT and Harvard, and Jose T. Saavedra, of Massachusetts Institute of Technology.

This research study was supported by Department of Health and Human Services/National Institutes of Health/National Institute of Allergy and Infectious Diseases grants AI072360, AI083214, HHSN272200900018C and U19AI110818.

原始論文：François Lebreton, Abigail L. Manson, Jose T. Saavedra, Timothy J. Straub, Ashlee M. Earl, Michael S. Gilmore. Tracing the Enterococci from Paleozoic Origins to the Hospital. Cell, 2017; DOI: 10.1016/j.cell.2017.04.027

引用自： Massachusetts Eye and Ear Infirmary. “Antibiotic-resistant microbes date back to 450 million years ago, well before the age of dinosaurs.” Geology Page, May 12, 2017