SlideShare a Scribd company logo
MECHANISM OF BIOFILM
-DR. MRINALINI
•INTRODUCTION
•HISTORY
•COMPOSITION
•SALIENT FEATURES
•BIOFILM FORMATION
•QUOROM SENSING
•NUTRITION INFLUENCE
•GENE TRANSFER
•ANTIBIOTIC RESISTANCE
•ROLE IN PATHOGENESIS
•CONCLUSION
CONTENT
A biofilm is defined as “an assemblage of microbial
cells that is irreversibly associated with a surface and
enclosed in a matrix of primarily polysaccharide
material
-Kelley, 2017
Earliest evidence of
organisms in the fossil:
form of stromatolites,
thought to be fossilized
remnants of
cyanobacterial biofilms
The oldest of these
fossils are dated at 3.4
billion years old
Anthony van Leeuwenhoek
(1632–1723) : aggregated
small animalcules in the
‘scurf of the teeth’
Louis Pasteur (1822–1895):
aggregates of bacteria as the
cause of wine becoming
acetic
Bill Costerton introduced
‘biofilm’ growth in medical
microbiology in 1985
Demonstrated increased
resistance of biofilm-
growing compared with
planktonically growing
bacteria
COMPOSITION
Non-cell material: Mineral crystal, Corrosion material, Clay, Blood
components etc( depending on the environment)
Can be thick or thin:
Depending on the
environment
Bacteria, Fungi and
Protista
Interspecies
Intraspecies Interkingdom
DEFENSE
NUTRIENT
RICH AREA
COOPERATIVE
BENEFITS
DEFAULT MODE
OF GROWTH
JEFFERSON KK
More resilient to stress
Persisters: Do not divide:
Resistant to many
antibiotics
Antibiotics: Cannot penetrate
EPS, Get neutralised,Bacteria
goes in physiologically
dormant state
Crossfeed: Close
proximity
Epstein:
Members of the community periodically wakes up
Send out scouts to test the environment
If adverse environment is not
present
Send signal to the remaining cells to resume
BIOFILM
FORMATION
1
REVERSIBLE
ATTACHMENT
2
IRREVERSIBLE
ATTACHMENT
MATURATION
DISPERSION
3
4
Van Der Wall
forces and
Secretory adhesive
molecule
Role of
environment
Role of gene
Initially: Conditioning film (Loeb & Neihof) composed of
polymers of the medium
Upregulation of gene
Moist environment Rough surface Less shear stress
Characteristics of cell: Flagella, Pili, Fimbriae, Glycocalyx
Expression of 800 genes have been
shown to be altered when single
bacterium species joins a biofilm
IRREVERSIBLE ATTACHMENT:
Production of gooey substance known as
Extrapolysaccharide (Network of sugar, proteins and nucelic
acids)
Further layer of microbes and Extrapolysachharide: Complex
3D-structure
WATER CHANNELS: Transport of nutrients, and oxygen to the cells
SEEDING DISPERSAL/SWARMING:
Either a clump of cells or individual cells burst out to seek a
new home.
Inner region liquifies so that the outer stationary bacteria swim
out leaving a hollow mound.
Programmed detachment :
Niduses of acute infection
As the bacteria in a biofilm are
protected by matrix host, host
immune system less likely mount a
response
Planktonic bacteria periodically
released: Each time immune
system becomes aware and
inflammatory response leading to
disease symptom:
CAUSE OF CHRONIC
RELAPSE IN INFECTION
If chronic bacteria form simply
kills its host, no longer have a
place to live
Infectious agent never kill the host,
neither host is ever able to fully get
rid of pathogens
Nutrition influence
Nutrient stress:
alterations in their cell
morphology and cell
surfaces, which
enhance adherence.
Oral cavity:
environment is less
extreme, and saliva
provides a constant
source of nutrients.
Catabolic cooperation
among oral bacteria
allows carbon and
nitrogen from salivary
glycoproteins to be
utilized.
The initial
conditioning film
Adherence of
pioneer bacteria
Production of
matrix
Bacterial
competition in the
later stages of
accumulation
The type and
availability
of nutrient
Process of cell–cell communication
that allows bacteria to share
information about cell density and
adjust gene expression accordingly
Enables bacteria to express
energetically expensive processes as
a collective only when the impact of
those processes on the environment
or on a host will be maximized
These processes include(Novick and Gissinger, 2008)
symbiosis, virulence, competence, conjugation, antibiotic
production, motility, sporulation, and biofilm formation
Gram-negative bacteria : acylated homoserine lactones as
autoinducers
Gram-positive bacteria: processed oligo-peptides
3 BASIC
PRINCIPLES
1. At low cell density : AIs diffuse away, and, therefore, are
present at concentrations below the threshold required for
detection.
At high cell density : the cumulative production of AIs leads to a
local high concentration, enabling detection and response (Kaplan
and Greenberg 1985)
2. AIs are detected by receptors that exist in the cytoplasm or in
the membrane
3. In addition to activating expression of genes , detection of AIs
results in activation of AI production (Novick et al. 1995)
GENE
TRANSFER
CONJUGATION
TRANSFORMATION
TRANSDUCTION
WHICH CAME FIRST??
Presence of gene-
encoding resistance to β-
lactam, tetracycline, and
glycopeptide antibiotics
in metagenome samples
of 30,000-year-old
permafrost.
Gut microbiome of a pre-
Columbian Andean
mummy from Peru (14C
dating of 980–1170 AD):
harbor genes with
homology to βlactam,
fosfomycin,
chloremphenicol,
Aminoglycosides,
macrolide, quinolones,
tetracycline and
vancomycin resistant
genes.
1st bacterial isolate
deposited in the UK
National Collection of
Type Cultures : strain of
Shigella flexneri that
killed a young soldier in
World War I.
Isolated in 1915, carry
resistance genes for
penicillin and
erythromycin when it
was revived and
sequenced in 2014
D’Costa et al,
2011
Santiago-
Rodriguez et al,
2015
Mather et al.,
2014
Most antibiotics in medical use: derived from or produced by a
group of soil-dwelling bacteria called the Actinomycetes.
Most notable genus for antibiotic production : Streptomyces
Producers of specialized metabolites (“natural products”):
antibiotics streptomycin, tetracycline, chloramphenicol,
erythromycin, and vancomycin.
 These organisms must be resistant to the antibiotics they
produce, or they would succumb to their own toxic metabolites.
Original sources for many of the antibiotic-resistance genes
circulating in the clinic today
•Antibiotic resistance in M. tuberculosis : exclusively by
spontaneous mutation.
•Staphylococcus aureus: Nasal commensal in 30% population.
1959: Introduction to methicillin, after 3 years Methicillin
resistant Staph aureus were reported.
Recently it became CA-MRSA(Community acquired)
•Most common distribution : beta lactamase gene
ROLE OF BIOFILM IN PATHOGENESIS
Staphylococcus
epidermidis: impede
the colonisation of
potentially pathogenic
bacteria through the
stimulation of host-
cell immune defences
and the prevention of
adhesion
Cystic fibrosis:
P. aeruginosa undergoe
s a transition from an
acute virulent pathogen
to a CF-adapted
pathogen, allowing it
to persist in the lung
for years or even
decades
Overproduction of the matrix polysaccharide alginate
Formation of a mucoid biofilm
Tolerates antibiotics, components of both the innate and adaptive
immune response, and resists phagocytosis
Persistence of these mucoid biofilms within the CF lung
Development of a distinct antibody response
Chronic inflammation mediated by granulocytes, and results in severe
damage to the lung tissue of CF patients
Localisation of acid
Acute infections:
generally treatable with
antibiotics
Infection often turns out to
be untreatable and will
develop into a chronic
state
Extreme resistance to antibiotics and many other
conventional antimicrobial agents.
Extreme capacity for evading the host defences.
Tolerance and Resistance
All bacteria can become resistant, irrespective of their growth
phenotypes, whereas only bacterial aggregates adapt by
exhibiting biofilm tolerance.
Caused by following factors:
3D architecture: presence of several layers of bacteria
promotes the development of nutrient and oxygen gradients and
slows down growth in the core of the aggregate
Matrix components can bind and/or neutralize antimicrobial
agents
Presence of areas within a biofilm that are inhabited by
stationary phase or even dormant bacteria
Frustrated phagocytosis: phagocytes do come in contact
with the bacteria in biofilms and they can even penetrate
biofilms. However, the bacteria in the biofilms are not killed.
Defence mechanism: chemical, as bacteria in biofilms can
produce compounds that disable or even kill PMNs
Quorom sensing
1. Cieplik F, Jakubovics NS, Buchalla W, Maisch T, Hellwig E,
Al-Ahmad A. Resistance Toward Chlorhexidine in Oral Bacteria–
Is There Cause for Concern?. Frontiers in microbiology. 2019;10.
2. Bjarnsholt T. The role of bacterial biofilms in chronic infections.
Apmis. 2013 May;121:1-58.
3. Davies J, Davies D. Origins and evolution of antibiotic
resistance. Microbiol. Mol. Biol. Rev.. 2010 Sep 1;74(3):417-33.
4. Donlan RM. Biofilms: microbial life on surfaces. Emerging
infectious diseases. 2002 Sep;8(9):881.
5. Crouzet M, Le Senechal C, Brözel VS, Costaglioli P, Barthe C,
Bonneu M, Garbay B, Vilain S. Exploring early steps in biofilm
formation: set-up of an experimental system for molecular studies.
BMC microbiology. 2014 Dec 1;14(1):253.
REFERENCES
6. Kampf G. Acquired resistance to chlorhexidine–is it time to
establish an ‘antiseptic stewardship’initiative?. Journal of
Hospital Infection. 2016 Nov 1;94(3):213-27.
7. Bowden GH, Li YH. Nutritional influences on biofilm
development. Advances in dental research. 1997 Apr;11(1):81-99.
8. Shintani M, Sanchez ZK, Kimbara K. Genomics of microbial
plasmids: classification and identification based on replication
and transfer systems and host taxonomy. Frontiers in
microbiology. 2015 Mar 31;6:242.
9. Miller MB, Bassler BL. Quorum sensing in bacteria. Annual
Reviews in Microbiology. 2001 Oct;55(1):165-99.
10. Rutherford ST, Bassler BL. Bacterial quorum sensing: its role
in virulence and possibilities for its control. Cold Spring Harbor
perspectives in medicine. 2012 Nov 1;2(11):a012427.
11. Chandki R, Banthia P, Banthia R. Biofilms: A microbial home.
Journal of Indian Society of Periodontology. 2011 Apr;15(2):111.
12. Okuda KI, Nagahori R, Yamada S, Sugimoto S, Sato C, Sato
M, Iwase T, Hashimoto K, Mizunoe Y. The composition and
structure of biofilms developed by Propionibacterium acnes
isolated from cardiac pacemaker devices. Frontiers in
microbiology. 2018 Feb 14;9:182.
13. Muhsin J, Ufaq T, Tahr H, Saadia A. Bacterial Biofilm: Its
composition, Formation and role in human infections. Journal of
Microbiology and Biotechnology. 2015;4:1-4.
14. Høiby N. A personal history of research on microbial biofilms
and biofilm infections. Pathogens and disease. 2014 Apr
1;70(3):205-11.

More Related Content

What's hot

Management of host plant resistance through immunization
Management of host plant resistance through immunizationManagement of host plant resistance through immunization
Management of host plant resistance through immunization
Anshul Arya
 
transcription and host-pathogen profile
transcription and host-pathogen profiletranscription and host-pathogen profile
transcription and host-pathogen profile
Mohammed Faisal Peeran
 
Mb 4 plant res @ sid
Mb 4 plant res @ sidMb 4 plant res @ sid
Mb 4 plant res @ sid
sidjena70
 
ISR IN PLANTS THROUGH FUNGAL BIOCONTROL AGENTS
ISR IN PLANTS THROUGH FUNGAL BIOCONTROL AGENTSISR IN PLANTS THROUGH FUNGAL BIOCONTROL AGENTS
ISR IN PLANTS THROUGH FUNGAL BIOCONTROL AGENTS
Jayappa Singanodi
 
Insect resistance
Insect resistanceInsect resistance
Insect resistance
indumathi balaji
 
Diseases resistance and defence mechanisms
Diseases resistance and defence  mechanismsDiseases resistance and defence  mechanisms
Diseases resistance and defence mechanisms
RAMALINGAM K
 
Genetics of plant disease
Genetics of plant diseaseGenetics of plant disease
Genetics of plant disease
Nada Sami
 
Cell Wall Associated Mechanisms of Disease Resistance & Susceptibility
Cell Wall Associated Mechanisms of Disease Resistance & SusceptibilityCell Wall Associated Mechanisms of Disease Resistance & Susceptibility
Cell Wall Associated Mechanisms of Disease Resistance & Susceptibility
Krishna Shah
 
mechanism of resistance in plant against insects
mechanism of resistance in plant against insectsmechanism of resistance in plant against insects
mechanism of resistance in plant against insectsaylove
 
Resistance ppt
Resistance pptResistance ppt
Resistance ppt
Sreshti Bagati
 
Avs defense responses of plants to pathogen
Avs defense responses of plants to pathogenAvs defense responses of plants to pathogen
Avs defense responses of plants to pathogen
AMOL SHITOLE
 
Molecular basis of insecticides resistance in insects with special reference ...
Molecular basis of insecticides resistance in insects with special reference ...Molecular basis of insecticides resistance in insects with special reference ...
Molecular basis of insecticides resistance in insects with special reference ...
Assam Agricultural University
 
How plants defend themselves against pathogens
How plants defend themselves against pathogensHow plants defend themselves against pathogens
How plants defend themselves against pathogens
Mohamed Barakat
 
insect resistance
insect resistanceinsect resistance
insect resistance
IGKV Raipur C.G.
 
Hypersensitivity reaction (HR) and mechanisms
Hypersensitivity reaction (HR) and mechanismsHypersensitivity reaction (HR) and mechanisms
Hypersensitivity reaction (HR) and mechanisms
N.H. Shankar Reddy
 
Biochemical plant defences(HR)
Biochemical plant defences(HR)Biochemical plant defences(HR)
Biochemical plant defences(HR)
dev9105
 
host-pathogen interaction in paddy blast
host-pathogen interaction in paddy blasthost-pathogen interaction in paddy blast
host-pathogen interaction in paddy blast
hema latha
 
Insect resisance ppt
Insect resisance  pptInsect resisance  ppt
Insect resisance ppt
Nikita Dewangan
 
"Bio - Warfare During Host Pathogen Interactions in Indigenous Crop Plants" b...
"Bio - Warfare During Host Pathogen Interactions in Indigenous Crop Plants" b..."Bio - Warfare During Host Pathogen Interactions in Indigenous Crop Plants" b...
"Bio - Warfare During Host Pathogen Interactions in Indigenous Crop Plants" b...
Md. Kamaruzzaman
 

What's hot (20)

Management of host plant resistance through immunization
Management of host plant resistance through immunizationManagement of host plant resistance through immunization
Management of host plant resistance through immunization
 
R GENES
R GENESR GENES
R GENES
 
transcription and host-pathogen profile
transcription and host-pathogen profiletranscription and host-pathogen profile
transcription and host-pathogen profile
 
Mb 4 plant res @ sid
Mb 4 plant res @ sidMb 4 plant res @ sid
Mb 4 plant res @ sid
 
ISR IN PLANTS THROUGH FUNGAL BIOCONTROL AGENTS
ISR IN PLANTS THROUGH FUNGAL BIOCONTROL AGENTSISR IN PLANTS THROUGH FUNGAL BIOCONTROL AGENTS
ISR IN PLANTS THROUGH FUNGAL BIOCONTROL AGENTS
 
Insect resistance
Insect resistanceInsect resistance
Insect resistance
 
Diseases resistance and defence mechanisms
Diseases resistance and defence  mechanismsDiseases resistance and defence  mechanisms
Diseases resistance and defence mechanisms
 
Genetics of plant disease
Genetics of plant diseaseGenetics of plant disease
Genetics of plant disease
 
Cell Wall Associated Mechanisms of Disease Resistance & Susceptibility
Cell Wall Associated Mechanisms of Disease Resistance & SusceptibilityCell Wall Associated Mechanisms of Disease Resistance & Susceptibility
Cell Wall Associated Mechanisms of Disease Resistance & Susceptibility
 
mechanism of resistance in plant against insects
mechanism of resistance in plant against insectsmechanism of resistance in plant against insects
mechanism of resistance in plant against insects
 
Resistance ppt
Resistance pptResistance ppt
Resistance ppt
 
Avs defense responses of plants to pathogen
Avs defense responses of plants to pathogenAvs defense responses of plants to pathogen
Avs defense responses of plants to pathogen
 
Molecular basis of insecticides resistance in insects with special reference ...
Molecular basis of insecticides resistance in insects with special reference ...Molecular basis of insecticides resistance in insects with special reference ...
Molecular basis of insecticides resistance in insects with special reference ...
 
How plants defend themselves against pathogens
How plants defend themselves against pathogensHow plants defend themselves against pathogens
How plants defend themselves against pathogens
 
insect resistance
insect resistanceinsect resistance
insect resistance
 
Hypersensitivity reaction (HR) and mechanisms
Hypersensitivity reaction (HR) and mechanismsHypersensitivity reaction (HR) and mechanisms
Hypersensitivity reaction (HR) and mechanisms
 
Biochemical plant defences(HR)
Biochemical plant defences(HR)Biochemical plant defences(HR)
Biochemical plant defences(HR)
 
host-pathogen interaction in paddy blast
host-pathogen interaction in paddy blasthost-pathogen interaction in paddy blast
host-pathogen interaction in paddy blast
 
Insect resisance ppt
Insect resisance  pptInsect resisance  ppt
Insect resisance ppt
 
"Bio - Warfare During Host Pathogen Interactions in Indigenous Crop Plants" b...
"Bio - Warfare During Host Pathogen Interactions in Indigenous Crop Plants" b..."Bio - Warfare During Host Pathogen Interactions in Indigenous Crop Plants" b...
"Bio - Warfare During Host Pathogen Interactions in Indigenous Crop Plants" b...
 

Similar to Biofilm basics

Endo microbiology
Endo microbiologyEndo microbiology
Endo microbiology
DR POOJA
 
Biofilms in otorhinolaryngology
Biofilms in otorhinolaryngologyBiofilms in otorhinolaryngology
Biofilms in otorhinolaryngology
Dr. Rajendra Singh Lakhawat
 
Biofilm.pptx
Biofilm.pptxBiofilm.pptx
Biofilm.pptx
SravanSagar4
 
Microbiology of endodontic disease
Microbiology of endodontic diseaseMicrobiology of endodontic disease
Microbiology of endodontic disease
Ashok Ayer
 
Morphology of bacteria lecture.pptx
Morphology of bacteria lecture.pptxMorphology of bacteria lecture.pptx
Morphology of bacteria lecture.pptx
mohammedkhateeb16
 
05 microbial biofilm_ii_2008
05 microbial biofilm_ii_200805 microbial biofilm_ii_2008
05 microbial biofilm_ii_2008MUBOSScz
 
05 microbial biofilm_ii_2008
05 microbial biofilm_ii_200805 microbial biofilm_ii_2008
05 microbial biofilm_ii_2008MUBOSScz
 
The gut microbiota — masters of host development and physiology
The gut microbiota — masters of host development and physiologyThe gut microbiota — masters of host development and physiology
The gut microbiota — masters of host development and physiologyAlfonso Enrique Islas Rodríguez
 
The gut microbiota — masters of host development and physiology
The gut microbiota — masters of host development and physiologyThe gut microbiota — masters of host development and physiology
The gut microbiota — masters of host development and physiologyAlfonso Enrique Islas Rodríguez
 
Study of alterations of bacterial membrane proteins involved in β lactam sens...
Study of alterations of bacterial membrane proteins involved in β lactam sens...Study of alterations of bacterial membrane proteins involved in β lactam sens...
Study of alterations of bacterial membrane proteins involved in β lactam sens...
Alexander Decker
 
Periodontal pathogens
Periodontal pathogensPeriodontal pathogens
Periodontal pathogens
Dr. vasavi reddy
 
Biofilms by krishanchand mahra
Biofilms by krishanchand mahraBiofilms by krishanchand mahra
Biofilms by krishanchand mahra
Dileep Banjare
 
Biofilms in chronic suppurative otitis media and cholesteatoma
Biofilms in chronic suppurative otitis media and cholesteatomaBiofilms in chronic suppurative otitis media and cholesteatoma
Biofilms in chronic suppurative otitis media and cholesteatoma
Md Roohia
 
Bacterial Virulence Factors in Periodontology
Bacterial Virulence Factors in PeriodontologyBacterial Virulence Factors in Periodontology
Bacterial Virulence Factors in Periodontology
Dr Ripunjay Tripathi
 
Biofilms- Dr. Richa Maurya
Biofilms- Dr. Richa MauryaBiofilms- Dr. Richa Maurya
Biofilms- Dr. Richa Maurya
Richa Maurya
 
Seminario biologia molecular - The correlation between biofilm formation capa...
Seminario biologia molecular - The correlation between biofilm formation capa...Seminario biologia molecular - The correlation between biofilm formation capa...
Seminario biologia molecular - The correlation between biofilm formation capa...
IsabellaArcila
 
Biofilms
Biofilms Biofilms
Biofilms
hannahgrazia
 
04 microbial biofilm_i_2008
04 microbial biofilm_i_200804 microbial biofilm_i_2008
04 microbial biofilm_i_2008MUBOSScz
 

Similar to Biofilm basics (20)

Endo microbiology
Endo microbiologyEndo microbiology
Endo microbiology
 
Biofilms in otorhinolaryngology
Biofilms in otorhinolaryngologyBiofilms in otorhinolaryngology
Biofilms in otorhinolaryngology
 
Biofilm.pptx
Biofilm.pptxBiofilm.pptx
Biofilm.pptx
 
Microbiology of endodontic disease
Microbiology of endodontic diseaseMicrobiology of endodontic disease
Microbiology of endodontic disease
 
Morphology of bacteria lecture.pptx
Morphology of bacteria lecture.pptxMorphology of bacteria lecture.pptx
Morphology of bacteria lecture.pptx
 
05 microbial biofilm_ii_2008
05 microbial biofilm_ii_200805 microbial biofilm_ii_2008
05 microbial biofilm_ii_2008
 
05 microbial biofilm_ii_2008
05 microbial biofilm_ii_200805 microbial biofilm_ii_2008
05 microbial biofilm_ii_2008
 
1.3 lovehate
1.3 lovehate1.3 lovehate
1.3 lovehate
 
The gut microbiota — masters of host development and physiology
The gut microbiota — masters of host development and physiologyThe gut microbiota — masters of host development and physiology
The gut microbiota — masters of host development and physiology
 
The gut microbiota — masters of host development and physiology
The gut microbiota — masters of host development and physiologyThe gut microbiota — masters of host development and physiology
The gut microbiota — masters of host development and physiology
 
Study of alterations of bacterial membrane proteins involved in β lactam sens...
Study of alterations of bacterial membrane proteins involved in β lactam sens...Study of alterations of bacterial membrane proteins involved in β lactam sens...
Study of alterations of bacterial membrane proteins involved in β lactam sens...
 
Periodontal pathogens
Periodontal pathogensPeriodontal pathogens
Periodontal pathogens
 
Biofilms by krishanchand mahra
Biofilms by krishanchand mahraBiofilms by krishanchand mahra
Biofilms by krishanchand mahra
 
Biofilms in chronic suppurative otitis media and cholesteatoma
Biofilms in chronic suppurative otitis media and cholesteatomaBiofilms in chronic suppurative otitis media and cholesteatoma
Biofilms in chronic suppurative otitis media and cholesteatoma
 
Bacterial Virulence Factors in Periodontology
Bacterial Virulence Factors in PeriodontologyBacterial Virulence Factors in Periodontology
Bacterial Virulence Factors in Periodontology
 
Biofilms- Dr. Richa Maurya
Biofilms- Dr. Richa MauryaBiofilms- Dr. Richa Maurya
Biofilms- Dr. Richa Maurya
 
Pathogenesis of infection
Pathogenesis of infectionPathogenesis of infection
Pathogenesis of infection
 
Seminario biologia molecular - The correlation between biofilm formation capa...
Seminario biologia molecular - The correlation between biofilm formation capa...Seminario biologia molecular - The correlation between biofilm formation capa...
Seminario biologia molecular - The correlation between biofilm formation capa...
 
Biofilms
Biofilms Biofilms
Biofilms
 
04 microbial biofilm_i_2008
04 microbial biofilm_i_200804 microbial biofilm_i_2008
04 microbial biofilm_i_2008
 

More from MrinaliniDr

History of dentistry: 20th century
History of dentistry: 20th centuryHistory of dentistry: 20th century
History of dentistry: 20th century
MrinaliniDr
 
Journal club: Lidocaine and Sodium hypochlorite interaction
Journal club: Lidocaine and Sodium hypochlorite interactionJournal club: Lidocaine and Sodium hypochlorite interaction
Journal club: Lidocaine and Sodium hypochlorite interaction
MrinaliniDr
 
David H Pashley: Clinical considerations of microleakage
David H Pashley: Clinical considerations of microleakageDavid H Pashley: Clinical considerations of microleakage
David H Pashley: Clinical considerations of microleakage
MrinaliniDr
 
Kakehashi samuel: In endodontics
Kakehashi samuel: In endodonticsKakehashi samuel: In endodontics
Kakehashi samuel: In endodontics
MrinaliniDr
 
How to Present Journal Club
How to Present Journal ClubHow to Present Journal Club
How to Present Journal Club
MrinaliniDr
 
Internal anatomy of pulp space
Internal anatomy of pulp spaceInternal anatomy of pulp space
Internal anatomy of pulp space
MrinaliniDr
 
Techniques of direct composite restoration
Techniques of direct composite restorationTechniques of direct composite restoration
Techniques of direct composite restoration
MrinaliniDr
 
Dentinal hypersensitivity
Dentinal hypersensitivityDentinal hypersensitivity
Dentinal hypersensitivity
MrinaliniDr
 
Management of biofilm in endodontics
Management of biofilm in endodonticsManagement of biofilm in endodontics
Management of biofilm in endodontics
MrinaliniDr
 
Management of open apex
Management of open apexManagement of open apex
Management of open apex
MrinaliniDr
 
Hand instruments in operative dentistry
Hand instruments in operative dentistryHand instruments in operative dentistry
Hand instruments in operative dentistry
MrinaliniDr
 
Ultrasonics basics and principles
Ultrasonics basics and principlesUltrasonics basics and principles
Ultrasonics basics and principles
MrinaliniDr
 

More from MrinaliniDr (12)

History of dentistry: 20th century
History of dentistry: 20th centuryHistory of dentistry: 20th century
History of dentistry: 20th century
 
Journal club: Lidocaine and Sodium hypochlorite interaction
Journal club: Lidocaine and Sodium hypochlorite interactionJournal club: Lidocaine and Sodium hypochlorite interaction
Journal club: Lidocaine and Sodium hypochlorite interaction
 
David H Pashley: Clinical considerations of microleakage
David H Pashley: Clinical considerations of microleakageDavid H Pashley: Clinical considerations of microleakage
David H Pashley: Clinical considerations of microleakage
 
Kakehashi samuel: In endodontics
Kakehashi samuel: In endodonticsKakehashi samuel: In endodontics
Kakehashi samuel: In endodontics
 
How to Present Journal Club
How to Present Journal ClubHow to Present Journal Club
How to Present Journal Club
 
Internal anatomy of pulp space
Internal anatomy of pulp spaceInternal anatomy of pulp space
Internal anatomy of pulp space
 
Techniques of direct composite restoration
Techniques of direct composite restorationTechniques of direct composite restoration
Techniques of direct composite restoration
 
Dentinal hypersensitivity
Dentinal hypersensitivityDentinal hypersensitivity
Dentinal hypersensitivity
 
Management of biofilm in endodontics
Management of biofilm in endodonticsManagement of biofilm in endodontics
Management of biofilm in endodontics
 
Management of open apex
Management of open apexManagement of open apex
Management of open apex
 
Hand instruments in operative dentistry
Hand instruments in operative dentistryHand instruments in operative dentistry
Hand instruments in operative dentistry
 
Ultrasonics basics and principles
Ultrasonics basics and principlesUltrasonics basics and principles
Ultrasonics basics and principles
 

Recently uploaded

Additional Benefits for Employee Website.pdf
Additional Benefits for Employee Website.pdfAdditional Benefits for Employee Website.pdf
Additional Benefits for Employee Website.pdf
joachimlavalley1
 
Palestine last event orientationfvgnh .pptx
Palestine last event orientationfvgnh .pptxPalestine last event orientationfvgnh .pptx
Palestine last event orientationfvgnh .pptx
RaedMohamed3
 
Overview on Edible Vaccine: Pros & Cons with Mechanism
Overview on Edible Vaccine: Pros & Cons with MechanismOverview on Edible Vaccine: Pros & Cons with Mechanism
Overview on Edible Vaccine: Pros & Cons with Mechanism
DeeptiGupta154
 
The geography of Taylor Swift - some ideas
The geography of Taylor Swift - some ideasThe geography of Taylor Swift - some ideas
The geography of Taylor Swift - some ideas
GeoBlogs
 
CLASS 11 CBSE B.St Project AIDS TO TRADE - INSURANCE
CLASS 11 CBSE B.St Project AIDS TO TRADE - INSURANCECLASS 11 CBSE B.St Project AIDS TO TRADE - INSURANCE
CLASS 11 CBSE B.St Project AIDS TO TRADE - INSURANCE
BhavyaRajput3
 
Chapter 3 - Islamic Banking Products and Services.pptx
Chapter 3 - Islamic Banking Products and Services.pptxChapter 3 - Islamic Banking Products and Services.pptx
Chapter 3 - Islamic Banking Products and Services.pptx
Mohd Adib Abd Muin, Senior Lecturer at Universiti Utara Malaysia
 
Honest Reviews of Tim Han LMA Course Program.pptx
Honest Reviews of Tim Han LMA Course Program.pptxHonest Reviews of Tim Han LMA Course Program.pptx
Honest Reviews of Tim Han LMA Course Program.pptx
timhan337
 
The French Revolution Class 9 Study Material pdf free download
The French Revolution Class 9 Study Material pdf free downloadThe French Revolution Class 9 Study Material pdf free download
The French Revolution Class 9 Study Material pdf free download
Vivekanand Anglo Vedic Academy
 
How to Make a Field invisible in Odoo 17
How to Make a Field invisible in Odoo 17How to Make a Field invisible in Odoo 17
How to Make a Field invisible in Odoo 17
Celine George
 
How libraries can support authors with open access requirements for UKRI fund...
How libraries can support authors with open access requirements for UKRI fund...How libraries can support authors with open access requirements for UKRI fund...
How libraries can support authors with open access requirements for UKRI fund...
Jisc
 
Unit 2- Research Aptitude (UGC NET Paper I).pdf
Unit 2- Research Aptitude (UGC NET Paper I).pdfUnit 2- Research Aptitude (UGC NET Paper I).pdf
Unit 2- Research Aptitude (UGC NET Paper I).pdf
Thiyagu K
 
A Strategic Approach: GenAI in Education
A Strategic Approach: GenAI in EducationA Strategic Approach: GenAI in Education
A Strategic Approach: GenAI in Education
Peter Windle
 
aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa
aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa
aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa
siemaillard
 
Embracing GenAI - A Strategic Imperative
Embracing GenAI - A Strategic ImperativeEmbracing GenAI - A Strategic Imperative
Embracing GenAI - A Strategic Imperative
Peter Windle
 
The Challenger.pdf DNHS Official Publication
The Challenger.pdf DNHS Official PublicationThe Challenger.pdf DNHS Official Publication
The Challenger.pdf DNHS Official Publication
Delapenabediema
 
CACJapan - GROUP Presentation 1- Wk 4.pdf
CACJapan - GROUP Presentation 1- Wk 4.pdfCACJapan - GROUP Presentation 1- Wk 4.pdf
CACJapan - GROUP Presentation 1- Wk 4.pdf
camakaiclarkmusic
 
The basics of sentences session 5pptx.pptx
The basics of sentences session 5pptx.pptxThe basics of sentences session 5pptx.pptx
The basics of sentences session 5pptx.pptx
heathfieldcps1
 
Polish students' mobility in the Czech Republic
Polish students' mobility in the Czech RepublicPolish students' mobility in the Czech Republic
Polish students' mobility in the Czech Republic
Anna Sz.
 
Model Attribute Check Company Auto Property
Model Attribute  Check Company Auto PropertyModel Attribute  Check Company Auto Property
Model Attribute Check Company Auto Property
Celine George
 
Language Across the Curriculm LAC B.Ed.
Language Across the  Curriculm LAC B.Ed.Language Across the  Curriculm LAC B.Ed.
Language Across the Curriculm LAC B.Ed.
Atul Kumar Singh
 

Recently uploaded (20)

Additional Benefits for Employee Website.pdf
Additional Benefits for Employee Website.pdfAdditional Benefits for Employee Website.pdf
Additional Benefits for Employee Website.pdf
 
Palestine last event orientationfvgnh .pptx
Palestine last event orientationfvgnh .pptxPalestine last event orientationfvgnh .pptx
Palestine last event orientationfvgnh .pptx
 
Overview on Edible Vaccine: Pros & Cons with Mechanism
Overview on Edible Vaccine: Pros & Cons with MechanismOverview on Edible Vaccine: Pros & Cons with Mechanism
Overview on Edible Vaccine: Pros & Cons with Mechanism
 
The geography of Taylor Swift - some ideas
The geography of Taylor Swift - some ideasThe geography of Taylor Swift - some ideas
The geography of Taylor Swift - some ideas
 
CLASS 11 CBSE B.St Project AIDS TO TRADE - INSURANCE
CLASS 11 CBSE B.St Project AIDS TO TRADE - INSURANCECLASS 11 CBSE B.St Project AIDS TO TRADE - INSURANCE
CLASS 11 CBSE B.St Project AIDS TO TRADE - INSURANCE
 
Chapter 3 - Islamic Banking Products and Services.pptx
Chapter 3 - Islamic Banking Products and Services.pptxChapter 3 - Islamic Banking Products and Services.pptx
Chapter 3 - Islamic Banking Products and Services.pptx
 
Honest Reviews of Tim Han LMA Course Program.pptx
Honest Reviews of Tim Han LMA Course Program.pptxHonest Reviews of Tim Han LMA Course Program.pptx
Honest Reviews of Tim Han LMA Course Program.pptx
 
The French Revolution Class 9 Study Material pdf free download
The French Revolution Class 9 Study Material pdf free downloadThe French Revolution Class 9 Study Material pdf free download
The French Revolution Class 9 Study Material pdf free download
 
How to Make a Field invisible in Odoo 17
How to Make a Field invisible in Odoo 17How to Make a Field invisible in Odoo 17
How to Make a Field invisible in Odoo 17
 
How libraries can support authors with open access requirements for UKRI fund...
How libraries can support authors with open access requirements for UKRI fund...How libraries can support authors with open access requirements for UKRI fund...
How libraries can support authors with open access requirements for UKRI fund...
 
Unit 2- Research Aptitude (UGC NET Paper I).pdf
Unit 2- Research Aptitude (UGC NET Paper I).pdfUnit 2- Research Aptitude (UGC NET Paper I).pdf
Unit 2- Research Aptitude (UGC NET Paper I).pdf
 
A Strategic Approach: GenAI in Education
A Strategic Approach: GenAI in EducationA Strategic Approach: GenAI in Education
A Strategic Approach: GenAI in Education
 
aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa
aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa
aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa
 
Embracing GenAI - A Strategic Imperative
Embracing GenAI - A Strategic ImperativeEmbracing GenAI - A Strategic Imperative
Embracing GenAI - A Strategic Imperative
 
The Challenger.pdf DNHS Official Publication
The Challenger.pdf DNHS Official PublicationThe Challenger.pdf DNHS Official Publication
The Challenger.pdf DNHS Official Publication
 
CACJapan - GROUP Presentation 1- Wk 4.pdf
CACJapan - GROUP Presentation 1- Wk 4.pdfCACJapan - GROUP Presentation 1- Wk 4.pdf
CACJapan - GROUP Presentation 1- Wk 4.pdf
 
The basics of sentences session 5pptx.pptx
The basics of sentences session 5pptx.pptxThe basics of sentences session 5pptx.pptx
The basics of sentences session 5pptx.pptx
 
Polish students' mobility in the Czech Republic
Polish students' mobility in the Czech RepublicPolish students' mobility in the Czech Republic
Polish students' mobility in the Czech Republic
 
Model Attribute Check Company Auto Property
Model Attribute  Check Company Auto PropertyModel Attribute  Check Company Auto Property
Model Attribute Check Company Auto Property
 
Language Across the Curriculm LAC B.Ed.
Language Across the  Curriculm LAC B.Ed.Language Across the  Curriculm LAC B.Ed.
Language Across the Curriculm LAC B.Ed.
 

Biofilm basics

  • 2. •INTRODUCTION •HISTORY •COMPOSITION •SALIENT FEATURES •BIOFILM FORMATION •QUOROM SENSING •NUTRITION INFLUENCE •GENE TRANSFER •ANTIBIOTIC RESISTANCE •ROLE IN PATHOGENESIS •CONCLUSION CONTENT
  • 3. A biofilm is defined as “an assemblage of microbial cells that is irreversibly associated with a surface and enclosed in a matrix of primarily polysaccharide material -Kelley, 2017
  • 4. Earliest evidence of organisms in the fossil: form of stromatolites, thought to be fossilized remnants of cyanobacterial biofilms The oldest of these fossils are dated at 3.4 billion years old
  • 5. Anthony van Leeuwenhoek (1632–1723) : aggregated small animalcules in the ‘scurf of the teeth’ Louis Pasteur (1822–1895): aggregates of bacteria as the cause of wine becoming acetic
  • 6. Bill Costerton introduced ‘biofilm’ growth in medical microbiology in 1985 Demonstrated increased resistance of biofilm- growing compared with planktonically growing bacteria
  • 7. COMPOSITION Non-cell material: Mineral crystal, Corrosion material, Clay, Blood components etc( depending on the environment)
  • 8. Can be thick or thin: Depending on the environment Bacteria, Fungi and Protista Interspecies Intraspecies Interkingdom
  • 10. More resilient to stress Persisters: Do not divide: Resistant to many antibiotics Antibiotics: Cannot penetrate EPS, Get neutralised,Bacteria goes in physiologically dormant state Crossfeed: Close proximity
  • 11. Epstein: Members of the community periodically wakes up Send out scouts to test the environment If adverse environment is not present Send signal to the remaining cells to resume
  • 14. Van Der Wall forces and Secretory adhesive molecule Role of environment Role of gene Initially: Conditioning film (Loeb & Neihof) composed of polymers of the medium
  • 15. Upregulation of gene Moist environment Rough surface Less shear stress Characteristics of cell: Flagella, Pili, Fimbriae, Glycocalyx Expression of 800 genes have been shown to be altered when single bacterium species joins a biofilm
  • 16. IRREVERSIBLE ATTACHMENT: Production of gooey substance known as Extrapolysaccharide (Network of sugar, proteins and nucelic acids)
  • 17. Further layer of microbes and Extrapolysachharide: Complex 3D-structure WATER CHANNELS: Transport of nutrients, and oxygen to the cells
  • 18. SEEDING DISPERSAL/SWARMING: Either a clump of cells or individual cells burst out to seek a new home. Inner region liquifies so that the outer stationary bacteria swim out leaving a hollow mound.
  • 19.
  • 20. Programmed detachment : Niduses of acute infection As the bacteria in a biofilm are protected by matrix host, host immune system less likely mount a response Planktonic bacteria periodically released: Each time immune system becomes aware and inflammatory response leading to disease symptom: CAUSE OF CHRONIC RELAPSE IN INFECTION
  • 21. If chronic bacteria form simply kills its host, no longer have a place to live Infectious agent never kill the host, neither host is ever able to fully get rid of pathogens
  • 22. Nutrition influence Nutrient stress: alterations in their cell morphology and cell surfaces, which enhance adherence. Oral cavity: environment is less extreme, and saliva provides a constant source of nutrients. Catabolic cooperation among oral bacteria allows carbon and nitrogen from salivary glycoproteins to be utilized.
  • 23. The initial conditioning film Adherence of pioneer bacteria Production of matrix Bacterial competition in the later stages of accumulation The type and availability of nutrient
  • 24.
  • 25. Process of cell–cell communication that allows bacteria to share information about cell density and adjust gene expression accordingly Enables bacteria to express energetically expensive processes as a collective only when the impact of those processes on the environment or on a host will be maximized
  • 26. These processes include(Novick and Gissinger, 2008) symbiosis, virulence, competence, conjugation, antibiotic production, motility, sporulation, and biofilm formation Gram-negative bacteria : acylated homoserine lactones as autoinducers Gram-positive bacteria: processed oligo-peptides
  • 27. 3 BASIC PRINCIPLES 1. At low cell density : AIs diffuse away, and, therefore, are present at concentrations below the threshold required for detection. At high cell density : the cumulative production of AIs leads to a local high concentration, enabling detection and response (Kaplan and Greenberg 1985) 2. AIs are detected by receptors that exist in the cytoplasm or in the membrane 3. In addition to activating expression of genes , detection of AIs results in activation of AI production (Novick et al. 1995)
  • 29.
  • 30.
  • 31.
  • 32.
  • 33.
  • 34.
  • 35.
  • 37. Presence of gene- encoding resistance to β- lactam, tetracycline, and glycopeptide antibiotics in metagenome samples of 30,000-year-old permafrost. Gut microbiome of a pre- Columbian Andean mummy from Peru (14C dating of 980–1170 AD): harbor genes with homology to βlactam, fosfomycin, chloremphenicol, Aminoglycosides, macrolide, quinolones, tetracycline and vancomycin resistant genes. 1st bacterial isolate deposited in the UK National Collection of Type Cultures : strain of Shigella flexneri that killed a young soldier in World War I. Isolated in 1915, carry resistance genes for penicillin and erythromycin when it was revived and sequenced in 2014 D’Costa et al, 2011 Santiago- Rodriguez et al, 2015 Mather et al., 2014
  • 38. Most antibiotics in medical use: derived from or produced by a group of soil-dwelling bacteria called the Actinomycetes. Most notable genus for antibiotic production : Streptomyces Producers of specialized metabolites (“natural products”): antibiotics streptomycin, tetracycline, chloramphenicol, erythromycin, and vancomycin.  These organisms must be resistant to the antibiotics they produce, or they would succumb to their own toxic metabolites. Original sources for many of the antibiotic-resistance genes circulating in the clinic today
  • 39. •Antibiotic resistance in M. tuberculosis : exclusively by spontaneous mutation. •Staphylococcus aureus: Nasal commensal in 30% population. 1959: Introduction to methicillin, after 3 years Methicillin resistant Staph aureus were reported. Recently it became CA-MRSA(Community acquired) •Most common distribution : beta lactamase gene
  • 40.
  • 41.
  • 42.
  • 43. ROLE OF BIOFILM IN PATHOGENESIS Staphylococcus epidermidis: impede the colonisation of potentially pathogenic bacteria through the stimulation of host- cell immune defences and the prevention of adhesion Cystic fibrosis: P. aeruginosa undergoe s a transition from an acute virulent pathogen to a CF-adapted pathogen, allowing it to persist in the lung for years or even decades
  • 44. Overproduction of the matrix polysaccharide alginate Formation of a mucoid biofilm Tolerates antibiotics, components of both the innate and adaptive immune response, and resists phagocytosis Persistence of these mucoid biofilms within the CF lung Development of a distinct antibody response Chronic inflammation mediated by granulocytes, and results in severe damage to the lung tissue of CF patients
  • 46. Acute infections: generally treatable with antibiotics Infection often turns out to be untreatable and will develop into a chronic state
  • 47. Extreme resistance to antibiotics and many other conventional antimicrobial agents. Extreme capacity for evading the host defences.
  • 48. Tolerance and Resistance All bacteria can become resistant, irrespective of their growth phenotypes, whereas only bacterial aggregates adapt by exhibiting biofilm tolerance. Caused by following factors: 3D architecture: presence of several layers of bacteria promotes the development of nutrient and oxygen gradients and slows down growth in the core of the aggregate Matrix components can bind and/or neutralize antimicrobial agents Presence of areas within a biofilm that are inhabited by stationary phase or even dormant bacteria
  • 49. Frustrated phagocytosis: phagocytes do come in contact with the bacteria in biofilms and they can even penetrate biofilms. However, the bacteria in the biofilms are not killed. Defence mechanism: chemical, as bacteria in biofilms can produce compounds that disable or even kill PMNs Quorom sensing
  • 50.
  • 51. 1. Cieplik F, Jakubovics NS, Buchalla W, Maisch T, Hellwig E, Al-Ahmad A. Resistance Toward Chlorhexidine in Oral Bacteria– Is There Cause for Concern?. Frontiers in microbiology. 2019;10. 2. Bjarnsholt T. The role of bacterial biofilms in chronic infections. Apmis. 2013 May;121:1-58. 3. Davies J, Davies D. Origins and evolution of antibiotic resistance. Microbiol. Mol. Biol. Rev.. 2010 Sep 1;74(3):417-33. 4. Donlan RM. Biofilms: microbial life on surfaces. Emerging infectious diseases. 2002 Sep;8(9):881. 5. Crouzet M, Le Senechal C, Brözel VS, Costaglioli P, Barthe C, Bonneu M, Garbay B, Vilain S. Exploring early steps in biofilm formation: set-up of an experimental system for molecular studies. BMC microbiology. 2014 Dec 1;14(1):253. REFERENCES
  • 52. 6. Kampf G. Acquired resistance to chlorhexidine–is it time to establish an ‘antiseptic stewardship’initiative?. Journal of Hospital Infection. 2016 Nov 1;94(3):213-27. 7. Bowden GH, Li YH. Nutritional influences on biofilm development. Advances in dental research. 1997 Apr;11(1):81-99. 8. Shintani M, Sanchez ZK, Kimbara K. Genomics of microbial plasmids: classification and identification based on replication and transfer systems and host taxonomy. Frontiers in microbiology. 2015 Mar 31;6:242. 9. Miller MB, Bassler BL. Quorum sensing in bacteria. Annual Reviews in Microbiology. 2001 Oct;55(1):165-99. 10. Rutherford ST, Bassler BL. Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harbor perspectives in medicine. 2012 Nov 1;2(11):a012427.
  • 53. 11. Chandki R, Banthia P, Banthia R. Biofilms: A microbial home. Journal of Indian Society of Periodontology. 2011 Apr;15(2):111. 12. Okuda KI, Nagahori R, Yamada S, Sugimoto S, Sato C, Sato M, Iwase T, Hashimoto K, Mizunoe Y. The composition and structure of biofilms developed by Propionibacterium acnes isolated from cardiac pacemaker devices. Frontiers in microbiology. 2018 Feb 14;9:182. 13. Muhsin J, Ufaq T, Tahr H, Saadia A. Bacterial Biofilm: Its composition, Formation and role in human infections. Journal of Microbiology and Biotechnology. 2015;4:1-4. 14. Høiby N. A personal history of research on microbial biofilms and biofilm infections. Pathogens and disease. 2014 Apr 1;70(3):205-11.

Editor's Notes

  1. Stromatolite, layered deposit, mainly of limestone, formed by the growth of blue-green algae (primitive one-celled organisms) For two billion years after they first appeared on Earth, these photosynthetic biofilms produced biomass in prodigious amounts with oxygen as a by-product. During that early period the oxygen was almost instantly tied up in chemical reactions with the components of a highly reducing atmosphere and landscape. But eventually oxygen production outstripped oxygen consumption and for the first time, at about 2.8 billion (check this date) years ago, free oxygen began to appear in the atmosphere. It was at this point that the first curious banded iron deposits, and later the extensive red bed iron deposits, were formed
  2. Protista: Algae, amoeba, slime moulds
  3. Caldwell et al.[14] highlighted four characteristics of biofilm as follows: • Autopoiesis – Must possess the ability to self‑organize • Homeostasis – Should resist environmental perturbations • Synergy – Must be more effective in association than in isolation Communality – Should respond to environmental changes as a unit rather than as single individuals
  4. Besides passive dispersal, brought about by shear stresses, A way to perceive environmental changes and gauge whether it is still beneficial to reside within the biofilm or whether it is time to resume a planktonic lifestyle. Biofilm dispersal can be the result of several cues, such as alterations in nutrient availability, oxygen fluctuations and increase of toxic products, or other stress-inducing conditions
  5. The phosphorylated response regulator activates transcription of the genes in the QS regulon (Fig. 1A). In some cases of Gram-positive bacterial QS, AIPs are transported back into the cell cytoplasm where they interact with transcription factors to modulate the transcription factor’s activity and, in turn, modulate gene expression changes (Fig. 1B)
  6. In his Nobel lecture, Fleming spoke of a hypothetical situation where a person self-treats a sore throat with antibiotics, “He buys some penicillin and gives himself, not enough to kill the streptococci but enough to educate them to resist penicillin.” He advised, “If you use penicillin, use enough.
  7. Tolerance means that bacteria are not killed, although they are unable to grow in the presence of the drug, whereas resistance allows bacteria to grow in the presence of antibiotics