What can bacteriophages do for us?

1. Antibiotic resistance.
Since discovery of the first antibiotic by Fleming, the pharmaceutical industry began to produce
penicillin for clinical use [1], and for 50 years the production of natural or synthetic antibiotics has been
continuous. However, the number of approved antibiotics by the Federal Drug Administration (FDA) has
been very reduced (Table 1), and hence we are faced with the fact that the number of new antibiotics is
decreasing while the number of resistant microorganisms is increasing, this being particularly so in the
case of ear infections due to pneumonia or meningitis. Natural antibiotics are produced by microbiota as
defence mechanism against other bacteria or fungi. In contrast, chemical synthesis has developed
important antibiotics such as fluoroquinolones, which that include Cipro or linezolid, which are effective
against some resistant strains of Staphylococcus, Streptococcus and Enterococcus [2]

There are many reasons for the antibiotic resistance phenomenon, the main one being abusive use over
the past twenty years. The resistance phenomenon represents not only a important healthcare issue but
also an economic problem, with an estimated cost of about 4000 million dollars per year [4]. The
importance of the problem is so great that in 1999 the European Union established a directive aimed at
coordinating the fight against antibiotic resistance within the different EU and the US government did
the same in 2000 [5, 6]. Today, penicillin fails to completely eradicate streptococci in up to 35 % of
patients [7]; the infections caused by Streptomyces agalactiae in pregnant women cannot be treated with
antibiotics because they increase the risk of abortion [8]. Methicillin-resistant S. aureus accounted for nearly 60 % of nosocomial S. aureus infections in 2001 and vancomycin-resistant Enterococcus faecium
have been reported [9].
Morover, the resistance phenomenon has gained importance not only in humans but also in cattle.
Thus, mastitis, caused mainly by S. agalactiae, Staphylococcus aureus, Streptococcus uberis and
Streptococcus dysgalactiae, generate losses estimated at between 1.7 and 2 billion dollars [10].
2. Phages.
2.1 Life cycle of the bacteriopaghes
A bacteriophage is a virus able to infect and kill bacteria that, in the case of lytic phages, interferes
unidirectionally with the normal bacterial metabolism, meaning that the bacteria enter a lytic cycle.
They are ubiquitous, obligate parasites and highly specific for their bacterial host. But what is an
enzybiotic? The most exact definition refers to a group of bacteriophage-associated enzymes that are
produced actively during the lytic cycle. These enzymes are able to degrade the peptidoglycan layer of
the bacterial cell wall. When this degradation has been carried out, new mature particles of
bacteriophages can be release from bacterial cell (Fig. 1).

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