Dr Angelika Gründling

Reader in Molecular Microbiology, Imperial College London,

 抗生物質を作り出す微生物を遺伝子レベルで探索し、配列や化学構造を同定できる新たな手法を開発できた点が大きいと思います。これまで培養できなかった微生物由来の物質が探せるようになります。

原文

“Antimicrobial resistance is a widespread problem that is slowly undermining our ability to treat common bacterial infections. The study by Ling et al., which describes the discovery of a new antibiotic that kills a large range of bacteria, raises our hopes that new antibiotics can be brought to the clinics in the not too distant future. The authors used an old strategy, looking for antimicrobials naturally produced by bacteria, but now with a new and important twist – in a new group of bacteria, which in the past were considered unculturable. The authors developed a method to propagate many of these ‘unculturable’ bacteria, which allowed them to tap them as a source of new antimicrobials. The great hope is now that many more new antibiotics can be uncovered in a similar manner. This study is also a great testimony for the technological advances that have been made in recent years and the speed with which one can now progress from the discovery of a new compound, to the identification of it chemical structure, its producer down to the genes coding for the enzymes required for its production.

“But before getting too carried away, it’s important to bear in mind that the new antibiotic only works against certain types of bacteria – such as MRSA and Streptococcus, and not on other multi-drug resistant pathogens such as E. coli, Klebsiella and Pseudomonas, which are all major causes of infection in humans. And of course the new antibiotic described in the paper has yet to be tested in humans. It is possible that it might not be as effective as hoped and there could be unforeseen side-effects that might limit its use.”

Dr Bob Lauder

Associate Dean in the Faculty of Health and Medicine, Lancaster University

新しい解析手法はコストや規模がそれほど大がかりではなく、現実的です。ただし、テイクソバクチンをヒトに投与するには、安全性や投与量を調べる必要があります。

原文

“The search for new antibiotics is an enormous challenge, and this work reports a major development in this arena. The importance of this arena is seen in the fact that the Longitude Prize 2014 chose antibiotic resistance as the topic for the prize from a wide range of really major social issues such as dementia and the provision of safe drinking water and food.

“Antibiotics made many conditions which were normally fatal, survivable, and so they have had an enormous impact on all of our lives. However, the widely recognised danger of antibiotic resistance, when bacteria develop resistance to an antibiotic rendering it much less useful, could undermine the progress in healthcare in this area made over the last 70 years.

“The costs of discovering, developing and testing a new antibiotic are huge and the financial risks are large as the antibiotic may have a limited lifespan if bacterial resistance develops. In fact few new antibiotics have been identified in the last 30 years and so this thorough study, is a welcome development in a field looking for new advances.

“The antibiotic identified is a bacterial product; produced by one soil bacteria to stop the growth of others. However, rather than grow these using conventional microbiological approaches, the approach taken by this group was to explore antibiotic production in the soil. This allowed them to access the products from bacteria which cannot be cultured in a lab. In fact it is likely than the vast majority of bacteria in soil cannot easily be cultured in the lab, and so this is likely to be an approach which is more widely used in the future to access novel antibiotics.

“The authors have conducted a detailed and thorough study which has reported the structure of this new antibiotic. Although this is a complex molecule it has a structure which is very likely to be suitable for synthesis, and hence production at a cost and scale which would be appropriate for a therapeutic material.

 “The report is very exciting but more work needs to be done before this new antibiotic can be used. While the initial toxicity studies reported suggest that it will likely be safe to use, that work needs to be developed. In addition more detailed studies will be needed to understand dosage, how much and how often should it be taken. The data suggest that it may be cleared from human plasma quite quickly.

“This new antibiotic appears to work in an interesting way, attacking key parts of the bacterial coat. While that may make it less likely that antibiotic resistance develops, that's not a certainty and we'll all need to use this new compound, and any others developed carefully, otherwise we risk wasting the potential this antibiotic has.”

Prof Roger Pickup

Associate Dean for Research, Lancaster University

非常にエキサイティングな手法が開発されました。今までなかったユニークな効果を発揮する抗生物質開発につながるかもしれません。ただし、医療や農業、畜産業における抗生物質の濫用をやめる、単なる風邪やインフルエンザで抗生物質を処方しないよう医学教育を徹底する、といったことは必要でしょう。

原文

“This is a very exciting development.  In the microbial world the uncultured majority, which constitutes >99.9% of all bacteria, are rarely exploited for their products.  Tapping into this vast resource by culture has been unfunded by government and industry, perhaps as it not considered exciting science in comparison to the characterisation of the microbial world by methods such as the next generation sequencing. Coupled with the reluctance of the pharmaceutical industry to fund the discovery of new antibiotics, the identification of this new antibiotic in this often unexplored sphere of microbiology is very exciting. This may lead to the discovery of more unique antibiotics that can come on line and replace, or work in tandem, with current therapies that fight infection, particularly those caused by bacteria currently resistant to the spectrum of antibiotics available to us at present.

“These ‘magic bullets’ have been discovered before only to have their effectiveness whittled away by the emergence of  bacteria resistant to those antibiotics. Although the prediction that developing bacterial resistance to Teixobactin will be more difficult due to its mode of action, precaution is a key principle here. Bacteria are tenacious in their ability to rapidly evolve and become resistant to antibiotics; lessons have been learnt from the current antibiotic crisis and these must implemented if Teixobactin is to be an effective readily available drug for fighting infection. These lessons include educating the public and medical professionals to prevent indiscriminate use of prescriptions (this drug will not fight cold and flu [viral diseases]), controlling its use in farming and animal production and using it as a second line defence if current antibiotics fail. Hopefully the pharmaceutical industry will take note of this discovery and direct funds to explore and exploit the bacteria that, at present, remain uncultured.”

●●●参考資料●●●

薬剤耐性菌をめぐる最近のイシュー

AFP通信（2014.12.17）

リオ五輪セーリング会場で薬剤耐性菌発見、医療廃棄物由来か

http://www.jiji.com/jc/a?g=afp_all&k=20141217032152a

AFP通信(2014.8.31)

高まる薬剤耐性菌リスク、インドの抗生物質多用が世界の問題に

http://www.afpbb.com/articles/-/3024540

産経新聞（2014.3.20）

4年で患者114人感染　多剤耐性菌、死者も　国立病院機構大阪医療センター

http://www.sankei.com/west/news/140320/wst1403200004-n1.html

薬剤耐性菌について

日本感染症学会

多剤耐性菌を正しく理解するための　Q&A

http://www.kansensho.or.jp/mrsa/100913publicqa.html

国立感染症研究所

薬剤耐性菌感染症

http://www.nih.go.jp/niid/ja/route/dr.html