The use of the viruses of bacteria, bacteriophages (phages), as therapeutic agents to treat bacterial infections began 20 years before the first clinical use of an antibiotic drug, but the introduction of broad-spectrum antibiotics in the 1940s rapidly eclipsed and displaced the development of phage therapeutics in much of the world.
therapeutic agents 약제
drug 약물
broad-spectrum 폭넓은 효능을 지닌
therapeutics 치료학
Phage therapy continued to be developed with ongoing use in the Soviet Union and Eastern Europe that continues to the present in Poland, Russia, and Georgia [1–3]. However, until the rising global dissemination of multidrug-resistant (MDR) bacterial infections [4], earnest interest in clinical application was not evident in Western Europe and the Americas, nor in much of the rest of the world.
therapy 치료
ongoing 계속 진행중인
multidrug-resistant 다제내성 or 다약제 내성
Multidrug-resistant organisms are bacteria that have become resistant to certain antibiotics, and these antibiotics can no longer be used to control or kill the bacteria.
Multidrug resistance combined with the slowing development of new antibiotics over the past few decades [5,6] threatens to further reduce treatment options for previously curable infections, so Western scientific and medical communities are now reengaging to develop phage therapies to help contend with this burgeoning problem.
Phages infect their specific bacterial hosts and in the lytic (or virulent) lifestyle high jack the machinery of the host cell to replicate and ultimately destroy the host, thus simultaneously producing progeny and killing the host. Phages are the most abundant biological entities on earth, with greater than 1030 individual virions estimated to be on the planet [7], and a well-described diversity that is still being discovered [8,9].
replicate 자기복제를 하다
lytic 용해의
simultaneously 동시에
progeny 자손
biological entity 생물학적 개체
This vast abundance and diversity of phages in nature provides a ready resource to mine for the selection of phages for a variety of purposes, including not only anti-bacterial therapy but also decontamination, infection control, detection, diagnosis, etc. Phage typing has been used in clinical laboratories to identify species and subtypes of bacteria (e.g., Salmonella, Bacillus anthracis, Staphylococcus, Brucella species) [10].
vast 어마어마한
decontamination 오염제거
detection 탐지
diagnosis 진단
clinical laboratories 임상의료업
There are a number of potential advantages of the use of phages as antibacterial therapeutics as have been discussed in numerous reviews and perspectives [11–15], including:
therapeutics 치료학
perspective 관점
(a) since lytic phages have entirely different mechanisms of killing bacteria than antibiotics, they are effective against MDR pathogens and, thus, can also often be used in combination with antibiotics, with frequent synergies;
antibiotic 항생제
entirely 전적으로
combination with ~와 결합하여
synergie 시너지효과
(b) since a phage often can infect only a single bacterial species or a subgroup within a bacterial species, phage therapeutics have high specificity (are narrow spectrum antimicrobials) and, thus, are expected to have little to no effect on normal microflora (in contrast with broad spectrum antibiotics);
specificity 특별함
spectrum 범위
microflora 미생물 무리
(c) since phages replicate on the target bacterium, they accumulate precisely where needed to eliminate pathogen cells at the site of infection (are self-replicating drugs);
replicate 복제하다
accumulate 늘어나다
precisely 바로
eliminate 없애다
(d) because phages are ubiquitous in the environment and generally easy to isolate, selecting a new phage active against a resistant bacterial strain is straightforward, making new antimicrobial discovery efficient and inexpensive;
ubiquitous 어디에나 있는
straightforward 복잡하지 않은
(e) since phages can encode enzymes that degrade biofilms that can be associated with difficult infections, they can provide access for other antimicrobials to surmount this barrier;
encode 암호화하다
degrade 분해되다
surmount ~ 의 위에 얹히다
(f) phage therapies have been used safely in thousands of humans in the former Soviet Union and Eastern Europe with very few side effects reported;
(g) phages with different specificities can be combined in cocktails to address the diversity of a pathogen or to target multiple bacterial pathogens and to address the emergence of resistance; (h) since phages coevolve with their hosts, they can be adapted to newly emergent resistant strains of the host bacterium; (i) since phages replicate to high titer on a bacterial host that is itself self-replicating, they are potentially less expensive to produce than other antibacterials; (j) phages have the potential to stably persist in vivo [16]; and (k) phages generally seem to be weak immunogens and, thus, adverse immunologic responses are unlikely (e.g., enhanced inflammatory response or phage inefficacy due to the potent neutralization by antibodies).
Potential limitations or challenges of phage therapy are: (a) high specificity, since the narrow lytic spectrum/host range of many phages means a single phage cannot be used to treat the diversity within a bacterial pathogen; (b) for some bacterial pathogens, different phage mixtures may be needed to treat the same bacterial disease in different geographical regions; (c) bacterial strains may gain resistance to phages because of alterations in their phage receptor(s) or by other mechanisms and, thus, diminish the effect of treatment (including during the course of a treatment); (d) phage cocktailing requires phage collections that are updated (through discovery or adaptation/engineering) to address newly emerged resistant variants; (e) collecting, maintaining, and using large banks of diverse phages can make safety testing and the regulatory path to an approved therapeutic more difficult and expensive; (f) multiplying the components of cocktails to expand their therapeutic spectrum will make large-scale production of phage therapeutics more complex and expensive; (g) the human immune response to phages used for therapy is not completely understood and could potentially impede efficacy or cause unwanted immune responses [11–15].