217
affect phage therapies because newer bacteriophages will be capable to destroy the
bacterial strains, which developed resistance against the phages used before.
Another advantage of phages is that if they are purified properly, they are harmless
for humans and they can be used as self dose at the site of infection. They are safe
for use even by immunocompromised patients because they do not cause a toxic
effect on the liver and kidneys. There are two options for phage therapies. They can
be either “personalized” which aims to target a causative pathogen that is causing an
infection in an individual patient or a combination of several strains of phages that
can be used to target more than one pathogenic bacterial species (Penchovsky and
Traykovska 2015; Jonczyk-Matysiak et al. 2019; Duckworth 1976; Pelfrene et al.
2016; Sharma et al. 2017; Domingo-Calap et al. 2016; Borysowski and Gorski 2008).
After the genome of a phage is injected in the bacterial cytoplasm, replication
inside the host follows by the use either of lytic or lysogenic mode. Phages use the
cellular machinery of the bacterium that they infect for some procedures as the synthesis of proteins and as energy generating systems. Indeed, few viruses can use
both lytic and lysogenic mode (Sharma et al. 2017). When lytic phages are used,
they can lyse and destroy the bacteria. Thus, progeny viruses are released. Then
phages render capable to be used again and to infect other bacteria. In contrast,
lysogenic phages should first integrate their genetic information into the genome of
the host and replicate along with the host. By this process, the host bacteria turn to
have new properties. Lytic phages are considered more suitable as therapeutic particles in comparison to lysogenic phages (Penchovsky and Traykovska 2015;
Domingo-Calap et al. 2016).
Unfortunately, there are cases where the failure of the treatment with the use of
phages is observed. Some of the reasons which may be related to phage therapy
failures are considered to be the way of phages reparation, the conditions in which
they stored, the way of their application, pharmacokinetics, different immune status
of patients, other drugs which are used in combination to phages and eating habits
(Jonczyk-Matysiak et al. 2019). During the last decade, one field where further
research is done for the use of phages is urinary tract infections. Urinary tract infections are the second most common cause of infectious diseases following pneumonia. It is well known that urinary tract infections affect predominately the woman
population due to some specific characteristics of females as the anatomy of the
genitourinary system as well as, the elderly whose immune system and microbiota
change during the years. The most common agent, which is blamed for urinary tract
infections is Escherichia coli, a Gram negative, facultative anaerobic bacterium
belonging to the family Enterobacteriaceae. A bacterium is normally found in intestines as a part of the normal gastrointestinal flora although, under some conditions,
it can become pathogenic and cause infections. E. coli is included in a list that was
published by the World Health Organization (WHO 2015). This list includes the
priority pathogens for which antibiotics should be discovered urgently. E. coli
belongs to the category of critical bacteria. The treatment options for urinary tract
infections generally involve the use of antibiotics.
However, the development of resistance is rapid and during the past decade, the
situation became worse due to the presence of the extended spectrum beta- lactamase
9 Drug Discovery for Targeting Drug Resistant Bacteria
affect phage therapies because newer bacteriophages will be capable to destroy the
bacterial strains, which developed resistance against the phages used before.
Another advantage of phages is that if they are purified properly, they are harmless
for humans and they can be used as self dose at the site of infection. They are safe
for use even by immunocompromised patients because they do not cause a toxic
effect on the liver and kidneys. There are two options for phage therapies. They can
be either “personalized” which aims to target a causative pathogen that is causing an
infection in an individual patient or a combination of several strains of phages that
can be used to target more than one pathogenic bacterial species (Penchovsky and
Traykovska 2015; Jonczyk-Matysiak et al. 2019; Duckworth 1976; Pelfrene et al.
2016; Sharma et al. 2017; Domingo-Calap et al. 2016; Borysowski and Gorski 2008).
After the genome of a phage is injected in the bacterial cytoplasm, replication
inside the host follows by the use either of lytic or lysogenic mode. Phages use the
cellular machinery of the bacterium that they infect for some procedures as the synthesis of proteins and as energy generating systems. Indeed, few viruses can use
both lytic and lysogenic mode (Sharma et al. 2017). When lytic phages are used,
they can lyse and destroy the bacteria. Thus, progeny viruses are released. Then
phages render capable to be used again and to infect other bacteria. In contrast,
lysogenic phages should first integrate their genetic information into the genome of
the host and replicate along with the host. By this process, the host bacteria turn to
have new properties. Lytic phages are considered more suitable as therapeutic particles in comparison to lysogenic phages (Penchovsky and Traykovska 2015;
Domingo-Calap et al. 2016).
Unfortunately, there are cases where the failure of the treatment with the use of
phages is observed. Some of the reasons which may be related to phage therapy
failures are considered to be the way of phages reparation, the conditions in which
they stored, the way of their application, pharmacokinetics, different immune status
of patients, other drugs which are used in combination to phages and eating habits
(Jonczyk-Matysiak et al. 2019). During the last decade, one field where further
research is done for the use of phages is urinary tract infections. Urinary tract infections are the second most common cause of infectious diseases following pneumonia. It is well known that urinary tract infections affect predominately the woman
population due to some specific characteristics of females as the anatomy of the
genitourinary system as well as, the elderly whose immune system and microbiota
change during the years. The most common agent, which is blamed for urinary tract
infections is Escherichia coli, a Gram negative, facultative anaerobic bacterium
belonging to the family Enterobacteriaceae. A bacterium is normally found in intestines as a part of the normal gastrointestinal flora although, under some conditions,
it can become pathogenic and cause infections. E. coli is included in a list that was
published by the World Health Organization (WHO 2015). This list includes the
priority pathogens for which antibiotics should be discovered urgently. E. coli
belongs to the category of critical bacteria. The treatment options for urinary tract
infections generally involve the use of antibiotics.
However, the development of resistance is rapid and during the past decade, the
situation became worse due to the presence of the extended spectrum beta- lactamase
9 Drug Discovery for Targeting Drug Resistant Bacteria