In the current scenario of emerging antimicrobial resistance there is a need of alternatives of antibiotics. A natural solution is available through bacteriophages which are easy to isolate, purify and use. Here a basic overview of bacteriophages in connection with increasing AMR has been presented for emphasizing their emphasis.
Bacteriophage therapy in the current scenario of emerging antimicrobial resistance
1. Taruna Anand*, Nitin Virmani, B.C. Bera, Medhavi Vashisth &
Priyanka
Corresponding author:tanandbt@gmail.com
Nationa Centre for veterinary Type Cultures, ICAR-NRCE, Hisar,
Haryana-125001
2. When microorganisms change in ways that
render the medications, used to cure the
infections they cause, ineffective
Superbugs
3. During year 2017,
› National educational campaign with a
slogan - “Be antibiotics aware” to prevent
the misuse of antibiotics by better
prescription services in human healthcare
and animal farms.
4. • Antibiotics may not be able to penetrate completely
into the biofilm:
• it may be degraded while trying to penetrate the
matrix
• they may get bound to charged molecules of
biofilm matrix
• Bacteria may respond to antibiotic induced stress by
altering
• gene expression
• Developing resistant skills
• The microenvironment of biofilm affetcs
• oxygen availability,
• pH,
• normal rapid binary fission
• These factors in turn affects the usual manner in
which antibiotics are effective
• Nutritional stress in biofilms leads to generation of a
heterologous population of slow growers and starved
persisters, which are extremely tolerant to antibiotics
and occupy the internal core of biofilms
5. (A) Therapeutic concentrations of antibiotics
are unable to penetrate biofilms due to poor
permeability and depressed metabolism of
biofilm constituents. Phage however, is able
to replicate within bacteria present in
biofilm. Next, biofilm instability occurs as
phage replicates. Finally, with the biofilm
disrupted, therapeutic concentrations of
antibiotic can better reach target bacteria,
and any cells resistant to phage infection
are expected to be more susceptible to
antibiotics
(Chan et al., 2018)
8. In order to avoid the dawn of a ‘postantibiotic era’, the WHO,
ECDP&C and IDSA have attempted to stimulate research into new
antimicrobial compounds and improve antibiotic stewardship.
Let’s go green and avoid antibiotics by using
› Probiotics
› Prebiotics
› Antimicrobial peptides
› Bacteriophages
› Organic acids
› Essential oils
› IgY
Alternative Antimicrobials
9. Alternatives Advantages Limitations
Vaccines • Prevent infections
• Immunological protection
• Costly
• Limited cross protection
Probiotics, Prebiotics &
Symbiotics
• Improve commensal gut bacterial health
• Prevent pathogen colonization
• Mixed efficacy
• Complex regulatory process
Phage therapy • Target specific
• Use of cocktails
• Efficacy with topical applications
• Can synergize with antibiotics
• Resistance development
• Highly specific
Lysins • Expanded species specificity
• Can synergize with antibiotics
• Few options against gram negative
bacteria available
Bacteriocins • Diverse repertoire
• Target specific
• Many are already established food grade
compounds
• Sensitive to proteolysis
Predatory bacteria • Effective against biofilms
• Can access recalcitrant infections
• Interaction with commensal microbiome is
unknown
Allen et al. 2014
10. https://www.uspharmacist.com/article/bacteriophages-beyond-antibiotics
Bacteriophages vs Antibiotics
Advantages
Phages are very specific in action
Replicate at the infection site/ Autodosing
Naturally occurring
Safe to use- haven’t demonstrated side effects
Minimal disruption of normal flora
Biofilm clearance
Active against antibiotic resistant bacteria also
Disadvantages
Not accessible to intracellular pathogens
Endotoxin removal from phage preparations is required
Additional research required for upcoming strategies of phage resistance and phage
neutralizing antibodies
Complicated regulatory issues
11. Lytic / Lysogenic
Only lytic phages desired in
phage therapy
BACTERIOPHAGES
(Green Bullets)
Lytic Cycle
Synthesis of phage
progeny
Phage Assembly
Lysis of host
Phage Release
12. Plaque is a clear zone of lysis produced by a single phage particle
13. Use of Personalized Bacteriophage-Based Therapeutic Cocktails To Treat a
Patient with a Disseminated Resistant Acinetobacter baumannii Infection
Schooley et al., 2017
Strathdee is an infectious disease epidemiologist at the UCSD, School of Medicine
and is now the co-director of the University’s newly established Center for Innovative
Phage Applications and Therapeutics (IPATH).
14. The phage banks may play an important role for therapeutic
purposes by timely presenting a panel of biologically active phages
which may be screened against case-specific infection causing
pathogens to select the most virulent or active phage against the
provocative infectious bacteria.
This needs a specialized diagnostic laboratory which should be
aware of the different phage characteristics.
A phage biologist prefers using lytic phages lacking any virulence,
antibiotic resistance associated or toxin genes for pursuing the
phage therapy.
The role of the phage repository becomes all the more important
when a resistant strain is encountered during the treatment regimen
as more effort would be involved in enrichment and purification of
phages against emergent strain.
15. Personalized medicine – It aims to use targeted medicines taking into account the
individual information to tailor the treatment and management of the patient. It is
used to ensure the best outcome and reduce the risk of side effects.
3/19/2020
16. Maximizing health benefits
Minimize unnecessary harms
Reduction of healthcare costs
16
18. Not all phages are suitable for therapy: there
should be no undesirable genes
The success depends on
› specificity of phage adsorption,
› tolerance of gastric acid by the phage,
› animal body temperature,
› dose (the host to phage ratio)
› route of administration and
› accessibility of target bacteria
19. Can educate community about importance of hygiene in
reducing infections
Encourage judicious use of antibiotics
Researchers and clinicians may provide information about
increasing antimicrobial resistance
Pharmacists to provide medication only by prescription
Undergraduate and post-graduate curiculum should include
topics of antimicrobial use and resistance
Active surveillance programme prevailing in community
Continuous hunt of safe alternatives of antibiotics
Infectious Diseases Society of America (IDSA)
European Centre for Disease Prevention and Control (ECDP&C)
While antibiotics still remain the mainstay for treating bacterial infections, researchers may have found new ways of treating infections.
The advantage to these approaches is that only the disease-causing bacterium is targeted by the treatment, and not the other members of the host’s commensal, beneficial microbial communities.
This is in contrast to most antibiotics, which generally have collateral effects on commensal bacteria in addition to the pathogenic target.
THIS SLIDE TO BE INCLUDED OR NOT ?
Overview about bacteriophages.
Brief lines about about their discovery and applications.
In a line also mention about their use in general biology understanding.
DO MENTION about ELIAVA Institute’s phage therapy. G. Eliava Institute of Bacteriophages, Microbiology and Virology, T'bilisi, Georgia
Basics of phage therapy
It has generally been thought that patients diagnosed with the same disease have the same root cause. They are often offered the same treatments. However, clinical experience tells us that patients do not all respond in the same way.
In reality, patients diagnosed with the same disease can have different causes of their disease. Therefore it is of great interest to try and develop medicines or treatments tailored towards to a specific group of patients or individuals
Sequencing enables the analysis of specific gene sequences for identifying a pathogenic agent
