1) Bacterial biofilms are resistant to antibiotics and contribute to chronic infections. Exposure to antibiotics can enhance biofilm formation in some bacteria and induce antibiotic resistance.
2) Alternative approaches to control biofilm infections include using natural products, enzymes to degrade the biofilm matrix, inhibiting quorum sensing, bioactive agents, nanoparticles, and photodynamic therapy.
3) Future options to address antibiotic resistance may involve novel anti-biofilm agents, gene editing technologies, and combinations of nanoparticles with antibiotics or photodynamic therapy.
2. Content
Introduction (definition + types + pathogenic properties)
Biofilms in nature
Infection associated with biofilms
Resistance To Antibiotics In Biofilms Communities
Enhancing Biofilm Formation and Resilience
Alternative approaches to control the biofilm related infections
2
4. Introduction
• This can described as combination of micro
organisms (mainly bacteria) have
aggregate to form a colony.
• These colonies attaches themselves to the
cell via the use of slime layer as a
protective barrier.
• There reason of existence in mainly to
cooperate with neighboring bacteria for
survival and growth.
4
5. Types of biofilms
• Bio films are mainly the combination of multitudes of
different types of bacteria which form a consortium.
• This will allow different bacteria to work together to
provide basic growth and protection but also to increase
their numbers which will allow the bio film to expand
further.
• One example is the combination of streptococcus
pyogenes and staphylococcus aureus that is linked to food
poisoning.
5
7. Pathogenic Properties
• It is to note that bio films are treatable but difficult to do
so as numerous bacteria have combined with themselves
to form a colony which consists of many and often
different techniques for pathogenesis.
• There includes from forming a protective layer of slim
composite that is difficult to penetrate and makes the use
of anti biotic is some case ineffective.
7
8. • There is evidence for the synthesis of bacterial toxins that further
weaken the cell surface and immune system to help better growth
and development.
• Bio-films are thus considered to be unpredictable to treat if ill
prepared and under informed.
• Diseases that are linked to these bio films includes:-
Tuberculosis
Cholera
Cystic Fibrosis
8
10. Bio Films in Nature
• BioFilms naturally are diverse and
consist more than few specific types
and variants of bacteria.
• They are also integrated with other
types of microbes like fungi,
protozoans etc, that contribute to the
environment and as well stabilize the
ecosystem to it’s optimum conditions.
10
11. • Unfortunately, due to human activity and research in modern
medicine with anti-biotic production, waste material are exposed to
certain bio films that have effected the genotype and phenotype of
various bacteria.
• Most notable change is the exposure of toxic waste water and
pollutants have modified the microbes in the bio films that enhanced
there capabilities to withstand harsh conditions which in turn
modify their physiology e.g. alternative cell wall components,
increased enzymatic activity, development of new strains of bacterial
clones etc.
• This can be concerning as it will overwhelm and quite possibly
destroy counteractive microbes (eg Fungi) to produce anti biotic
chemicals thus indirectly increase the pathogenic abilities.
11
13. Infections Associated With Biofilms
• Approximately 80% of chronic and recurrent microbial
infections in the human body are due to bacterial biofilm.
• Microbial cells within biofilms have shown 10–1000 times
more antibiotics resistance than the planktonic cells.
• Biofilm is formed in diverse environmental niches, including
freshwater rivers, rocks, deep-sea vents and hydrothermal
hot springs.
13
14. • Biofilm-related infections can be broadly divided into two types.
• The biofilms may be formed on the abiotic surfaces, especially
infections associated with indwelling medical devices and native
biofilm infections of host tissue.
• Urinary tract and bloodstream infections can be caused by the biofilm
initially formed on medical implants, such as heart valves, catheters,
contact lenses, joint prostheses, intrauterine devices and dental unit.
• These infections can only be treated by removal of the implants which
not only increasing the cost of the treatment but also it becomes
problematic for patients
14
15. • Host tissue related biofilm infections are often chronic, including
1. chronic lung infections of cystic fibrosis patients
2. chronic osteomyelitis
3. chronic prostatitis
4. chronic rhinosinusitis
5. chronic otitis media
6. chronic wounds
7. recurrent urinary tract infection
8. Endocarditis
9. periodontitis
15
18. Resistance To Antibiotics In Biofilms
Communities
• Antibiotic resistance of bacteria in the biofilm
communities contributes to the chronic infections.
• Repeated exposure of ceftazidime in biofilm-growing
Pseudomonas aeruginosa developed the conventional type
of intrinsic antibiotic resistance in biofilms infections.
18
19. • In biofilm communities, antibiotics resistance appears due to
various strategies such as
1. Slow or incomplete penetration of the antibiotics into the biofilm
2. An altered chemical microenvironment within the biofilm
3. A subpopulation of micro-organisms in a biofilm (a type of cell
differentiation like to spore formation)
• Multicellularity nature of biofilm bacterial communities is
responsible for antibiotics resistance
• if we can disrupt any step in the formation of multicellular
structure of the biofilms than antibiotics efficacy and the host
defences might be increased leading to quick treatment of this
persistent infection.
19
20. • One of the antibiotics resistance mechanisms of biofilms
communities is the uptake of resistance genes by horizontal
gene transfer.
• EPS might quench the activity of antibiotics that diffuse
through the biofilms via diffusion–reaction inhibition
phenomenon, which may chelates the antibiotics by complex
formation or degrade through enzymatically based reactions.
• Stationary phase (a slow or non-growth phase of the
bacterial life cycle) and (VBNC state or a state of dormancy)
are the ways of survival
20
23. • Exposure of Campylobacter jejuni, to various antibiotics led to
enhanced biofilm formation in antibiotic susceptible strains.
• A similar effect was observed for Leptospira spp. after treatment with
doxycycline and tetracycline.
23
24. • Streptococcus intermedius, showed increased biofilm formation upon exposure to
ampicillin (bacterial cell wall synthesis inhibitor), ciprofloxacin (transcription
inhibitor), and tetracycline (translation inhibitor).
• ciprofloxacin, azithromycin (protein synthesis inhibitor) and ceftazidime
(bacterial cell wall inhibitor), were found to decrease the expression of quorum-
sensing related genes in P. aeruginosa.
• such effects can be both strain- and antibiotic-specific, and, therefore, hard to
predict.
24
25. • Changes in the morphology of biofilm cells were observed in Klebsiella
pneumoniae biofilms in the presence of β-lactam carbapenems (cell wall
inhibitors) imipenem, meropenem and doripenem.
• Beta-lactam antibiotics methicillin, ampicillin, amoxicillin, and cloxacillin
were shown to induce biofilm formation in Staphylococcus aureus strains,
(MRSA).
25
27. Alternative Therapy
• Classical antibiotics chemotherapy is unable to completely
eradicate bacterial cells
• Because they are situated in the central region of the biofilm
• alternative strategies and novel anti-biofilm agents to
overcome the drug resistance of bacterial biofilm
communities
27
29. 1. Natural products
• D-amino acids and Polyamine
norspermidine; induced the
dispersal of mature biofilms which
could prevent biofilm formation in
S. aureus and E. coli
• These molecules could be used as
anti-biofilm agent in the biofilm
dispersal strategy.
29
30. 2. Matrix degrading enzyme
• Enzymes : (DNase I, Dispersin B (DspB) and a-amylase.
• It allows the increased penetration of antibiotics which
enhances the antibiotics efficiency.
• DNase I, DspB and α-amylase degrade eDNA, biofilm matrix
and exopolysaccharide respectively.
• They inhibit and degrade the mature biofilms in S. aureus,
Vibrio cholerae and P. aeruginosa.
30
31. 3. Quorum sensing (QS)
• Halogenated furanone isolated from Delisea pulchra (marine algae) interrupt
the bacterial QS signalling .
• ginseng extract, garlic extract, usnic acid and azithromycin possesses inhibitory
activity against bacterial and fungal biofilms.
• nitric oxide (NO) disperse the biofilms in P. aeruginosa and enhances the
activity of antimicrobial compounds.
31
33. 4. Bioactive agents
• Bacterial and actinomycetes produce bioactive
natural compounds with antibiofilm properties.
• Methanolic extract of a coral-associated
actinomycete reduce biofilm of S. aureus .
• 4-phenylbutanoic acid show high antibiofilm
activity against Gram positive and Gram
negative bacteria .
• Azadiracta indica (Neem) and Acacia extracts
showed antimicrobial effect against S.mutans
and S. faecalis
33
34. 5. Nanoparticles
• Limitations of the conventional antibiotic treatments (reduced
penetration and retention in cell or biofilm) were overcome by nano
particles.
• Suppressive effect of CaF2-NPs on genes associated with virulence
factors (vicR, gtfC, ftf, spaP, comDE) of S. mutans suggesting the
suppression of
1. glucan synthesis
2. cell adhesion
3. acid production
4. acid tolerance
5. quorum sensing
34
35. 6. Photodynamic therapy (PDT)
• PDT has sufficiently reduced the clinically-relevant microbes,
such as drug resistant Gram-positive and Gram-negative
bacteria .
• PDT has significant advantages over conventional treatment:
1. selective binding to the membranes of pathogenic cells
2. accurate delivery of light to the affected tissue
3. maximal damage of microbes
4. minimal damage of the host.
35
37. Conclusion and future prospects
• Bacterial antibiotic resistance is also one of the
consequences of the bacterial biofilm communities which
contribute to the chronic infections.
• Emergence and spreading of multidrug resistant, have
worsened the current situation across the globe.
• Nanoparticles based antibiotics formulation, novel anti-
biofilm agents, CRISPRi gene editing technologies and
photodynamic therapy might be the future options.
37
38. References
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492572/#:~:text=As
%20discussed%20above%2C%20antibiotics%20have,is%20therefore%
20of%20great%20concern
• Kaplan J. B. (2011). Antibiotic-induced biofilm formation. Int. J.
Artif. Organs 34 737–751. 10.5301/ijao.5000027
• Teh A. H. T., Lee S. M., Dykes G. A. (2019). Growth in the presence of
specific antibiotics induces biofilm formation by a Campylobacter
jejuni strain sensitive to them but not in resistant strains. J. Glob.
Antimicrob. Resist. 18 55–58. 10.1016/j.jgar.2019.05.020
• Sharma, D., Misba, L., & Khan, A. U. (2019). Antibiotics versus
biofilm: an Emerging Battleground in Microbial
Communities. Antimicrobial Resistance & Infection Control, 8(1).
https://doi.org/10.1186/s13756-019-0533-3
38
Editor's Notes
Resistance mechanisms of biofilm communities are not similar as the planktonic ones such as target site mutations, lower cell permeability, efflux pumps, drug modifying enzymes and drug neutralizing proteins.
viable-but-nonculturable state
Resilience is the ability to withstand adversity and bounce back from difficult life events
Campylobacter jejuni : a bacterium often associated with human gastroenteritis
Streptococcus intermedius, a commensal bacterium associated with periodontitis , fatal purulent infections and brain and liver abscesses
periodontitis
inflammation of the tissue around the teeth, often causing shrinkage of the gums and loosening of the teeth.
morphology of biofilm cells (i.e., rounding, blebbing, and alteration of cell size)
Environmental DNA (eDNA) is nuclear or mitochondrial DNA that is released from an organism into the environment.
Streptococcus mutans
nano-formulations which have the ability to cross the biological barrier.