バクテリオファージはフラッキングによる被害を減少させる可能性がある、極めて議論の分かれる手法

化石燃料汚染を抑制するバイオテクノロジー

The rise of shale oil & gas production in the US has been a major change in the global energy landscape. It single-handedly reverted the decline in US production, as conventional oil & gas fields production started declining in the 1970s.

出典: EIA

シェール油の生産には膨大な水が必要で、掘削井戸の刺激に13億バレルの水が使用され、年間で生産された水（PW）は16億バレルに上ります。

この生産された水（PW）は、シェール産業の主な環境廃棄物です（炭素やメタン排出は除く）。イオン（塩分）や揮発性有機化合物（VOCs）、炭化水素、その他の有機化合物が含まれ、非常に複雑な化学混合物となっています。この混合物は細菌の繁殖に最適な環境でもあります。

現在、PWはしばしば処理され油井に再注入され、シェール油層の圧力維持に利用されます。しかし、細菌の増殖はさまざまな問題を引き起こす可能性があります。たとえば、Pseudomonas aeruginosa が鉄を酸化して配管腐食を起こしたり、Bacillus megaterium が炭化水素を分解したりしますが、これらはシェール油採取の目的そのものです。

この問題を解決するために、PWは酸化剤（オゾン、過マンガン酸カリウム、過酸化水素）やグルタルアルデヒド、次亜塩素酸ナトリウム、過酢酸、その他の殺菌剤など、さまざまな方法で消毒されますが、これらの化合物は製造にエネルギーを多く要し、環境汚染の原因にもなり得ます。

さらに、細菌はこれらの処置に迅速に適応し、効果を維持するためにますます高濃度が必要となります。これは、病院での抗生物質耐性の出現に似ています。

新しいタイプの細菌殺菌剤として、バクテリオファージと呼ばれるウイルスのクラスが活用できる可能性があります。

私たちは「Living抗生物質の創造：BiomX (PHGE ) vs Armata」において、抗生物質耐性と治療の文脈でバクテリオファージについて議論しました。

バクテリオファージ対細菌

Bacteriophages are viruses specialized in infecting bacteria and are harmless to other lifeforms. They multiply by injecting their genetic material into the bacteria, forcing it to make more bacteriophages.

They function through a system of ‘lock and key’, primarily depending on the interaction of the phage with receptors found on the bacterial cell surface. This means that most bacteriophages are ultra-specialized, often targeting only one species of bacteria.

As bacteriophages are themselves “alive”, they can co-evolve with the bacteria and adapt to most resistance that would appear when using chemicals or antibiotics.

出典: Britannica

バクテリオファージは塩水や高温、極端なpHなどの過酷な環境でも機能することが知られており、したがってシェール産水中の細菌を殺すのに最適な選択肢となり得ます。

バクテリオファージによる廃水浄化

Researchers at the University of Texas and Universidad Nacional Pedro Henríquez Ureña in the Dominican Republic have investigated the potential of bacteriophages against Pseudomonas aeruginosa and Bacillus megaterium. The two bacteria were chosen for their contribution to problems in shale water processing and for the commercial availability of bacteriophages targeting them.

The researchers demonstrated that in the presence of phages, P. aeruginosa failed to proliferate in the wastewater. For B. megaterium, a mix of 2 phage species called Slash and Palmer has proven to be more effective than a single phage treatment to eliminate the bacteria.

バクテリオファージの将来の進展

In order for this solution to become more widely adopted, mass production of the phages and protocol to incorporate them in shale wastewater processing are needed.

Another limitation is that each bacteriophage is very specific to a bacterial species, so targeting other bacteria will require a larger phage bank and more commercially available phages than currently available.

いずれにせよ、これはシェール産水の処理において生物学的オプションの可能性を示しており、汚染性かつエネルギー集約的な化学処理の必要性を大幅に削減します。

バクテリオファージ企業

Many companies are working on bacteriophage technology, but only a few are publicly traded. Most are focused on therapeutic applications, as these tend to be a much more profitable market, although also one facing much stricter regulations.

出典: Pharmaceutical Technology

1. BiomX

BiomX is a bacteriophage company focused on treating antibiotic-resistant infections related to cystic fibrosis and Staphylococcus aureus infections in diabetic foot osteomyelitis (DFO).

There are 17,000 cystic fibrosis patients in the US and Western Europe with chronic PsA infections, creating a potential commercial opportunity of $1.6 billion worldwide.

DFO is the cause of the majority of 160K lower limb amputations in diabetic patients annually in the US, creating a potential commercial opportunity of $2 billion worldwide.

出典: Biomx

In 2024年3月, it merged with its competitor Adaptive Phage Therapeutics, giving it 2 products in phase II of clinical trials, with results expected in 2025.

出典: Biomx

Initial clinical results have been promising, including penetration of biofilms (the key problem in DFO treatment failures) and a good safety profile, as well as no development of resistance by the bacteria.

BiomX is also looking at treatment for skin infections (atopic dermatitis), with research still in the pre-clinical stage.

2. PHAXIAM Therapeutics (PHXM.PA)

France-based Phaxiam is the result of the merger in 2023年6月 of phage-focused companies Pherecydes Pharma and Erytech Pharma .

The company pipeline is focused on bacteria also targeted by BiomX, Staphylococcus aureus, and Pseudomonas aeruginosa, as well as Escherichia coli.

Most of the phase 2 clinical trials are expected to be launched in 2025.

出典: Phaxiam

The company’s R&D pipeline seems promising, but the decline in stock price over the last few years indicates investors’ concerns regarding its financial stability. In 2024年4月, it announced having a cash runway going only into 2024年9月, and is “Reviewing options to further extend cash runway”.