BIOFILMS AND QUORUM SENSING , SOCIAL MICROBIOLOGY - PowerPoint PPT Presentation

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BIOFILMS AND QUORUM SENSING , SOCIAL MICROBIOLOGY

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Title: BIOFILMS AND QUORUM SENSING , SOCIAL MICROBIOLOGY


1
Socio-microbiologybiofilms and quorum sensing in
infectious diseases
  • Dr.T.V.Rao MD

2
Sociomicrobiology
  • Sociomicrobiology" is part of the broader
    discipline "Microbiology", the study of organisms
    (bacteria, yeast, molds, viruses and protists)
    that cannot be observed with the naked eye, but
    having critical mechanisms for propagation.

3
Sociomicrobiology
  • The term "sociomicrobiology" was introduced by
    Matt Parsek Peter Greenberg in 2005 (Trends in
    Microbiology, 1327-33) and refers to the group
    behavior of micro-organisms, Two topics that
    form the core of sociomicrobiological research
    are microbial biofilm formation and cell-cell
    communication (quorum sensing).

4
Introduction
  • Quorum sensing is cell to cell signaling
    mechanism that enables the bacteria to
    collectively control gene expression.
  • This type of bacterial communication is achieved
    only at higher cell densities.
  • Bacteria release various types of molecules
    called as auto inducers in the extracellular
    medium, these molecules are mediators of quorum
    sensing.
  • When concentration of these signaling molecules
    exceed a particular threshold value, these
    molecules are internalized in the cell and
    activate particular set of genes in all
    bacterial population, such as genes responsible
    for virulence, competence, stationary phase etc .

5
Sociomicrobiology advances the understanding
microbes
  • The study of group behavior in microbes
  • Debate over environmental vs. genetic
    determinates
  • Biofilms and quorum sensing
  • Model for dissecting social behavior at a
    genetic level

6
Bacteria are dynamic creatures
  • Bacteria are dynamic creatures that are able to
    regulate their metabolism and lifestyle in
    response to a variety of environmental cues.
    These cues include changes in their chemical,
    physical, and biological surroundings. In recent
    decades, microbiologists have come to appreciate
    that bacteria are even able to recognize changes
    in their own population density. Cell
    density-dependent regulation has been termed
    "quorum sensing."
  • iosynthetic and regulatory prodigiosin mutants
    of Serratia

7
Microbes run in our body as normal flora
  • Microbes run much of our body. The human micro
    biome in our gut, mouth, skin, and elsewhere,
    harbors 3,000 kinds of bacteria with 3 million
    distinct genes. (Our own cells struggle by on
    only 18,000 genes or so.)This biotech century
    will be microbe enhanced and maybe microbe
    inspired.Confronting a difficult problem we
    might fruitfully ask, What would a microbe do?

8
Microbes do have social life and well adopted

Why do we work on it?
  • Models to understand biology of sociality
  • To develop new medicines to treat devastating
    bacterial infections
  • ?Understanding bacteria
  • Sociomicrobiology
  • The new science of
  • Tools for synthetic biology

9
Genetics x environment
  • In the past decade, significant debate has
    surrounded the relative contributions of genetic
    determinants versus environmental conditions to
    certain types of human behavior

10
What is a Biofilm?
  • A structured community of bacterial cells
    enclosed in a self-produced polymeric matrix.
  • -Biofilms are a protective mode of growth that
    allows survival in hostile environments.
  • -Bacteria in biofilms are inherently resistant to
    killing.

11
Biofilms are .
  • Biofilms are multicellular aggregates of bacteria
    and yeast that congregate on surfaces.
  • Biofilm may form on any surface exposed to
    biofilm-forming bacteria and some amount of
    water.
  • Biofilms are formed to protect the bacteria from
    host defenses, antibiotics, and from harsh
    environmental conditions.

12
Biofilms are communities of Microorganisms
  • Biofilms are communities of microorganisms that
    develop on surfaces in most natural and
    artificial environments. Biofilm maturation
    requires cell contact with a surface and
    cell-cell adhesion counteracting the shear forces
    of the environment. Biofilms are characterized by
    a surface covered by a high number of cells (a
    film) encased in a self-produced extra cellular
    matrix, are highly heterogeneous environment,
    both at structural, physiological and specific
    levels and biofilm bacteria express still
    under-explored specific biological properties
    such as a characteristic increased tolerance to
    biocides

13
Where are Biofilms Found?
  • Biofilms are found almost everywhere in nature,
    including rivers, lakes, soil, water pipes, and
    even inside the human body
  • Bacterial biofilms are often a cause of
    infections associated with medical implants such
    as catheters and IV lines and other medical
    devices.

14
Biofilms are concern in every aspect of life
15
The Dynamics of Growing Biofilm
  • Quorum Sensing
  • What is it?
  • How does it work?
  • Heterogeneous structures
  • How do these cells use polymer gel for
    locomotion?
  • What are the mechanisms of pattern (structure)
    formation?
  • Why is polymer gel so effective as a protective
    environment?

16
Biofilms are advantageous to microorganisms
  • Biofilms are important survival mechanisms for
    bacterial cells. According to in vitro studies,
    they can avoid attack by host defenses. it is
    difficult for phagocytic cells to engulf bacteria
    in biofilms. Also, biofilms are much more
    resistant than planktonic cells to antimicrobial
    agents. The bacteria within the biofilm remain
    healthy, and the biofilm can regrow. Repeated use
    of antimicrobial agents on biofilms can cause
    bacteria within the biofilm to develop an
    increased resistance to biocides.

17
Biofilms in medicine
  • In medicine, biofilms spreading along implanted
    tubes or wires can lead to pernicious infections
    in patients. Biofilms on floors and counters can
    make sanitation difficult in food preparation
    areas.
  • Dental plaque is a yellowish biofilm that build
    up on the teeth. If not removed regularly, it can
    lead to dental caries.

18
Why Research on Biofilms?
  • Due to the morphology of biofilms, bacteria
    capable of forming them are highly resistant to
    antibiotics, making treatment very difficult.
  • In the US alone, one million nosocomial (hospital
    acquired) infections each year are caused by
    bacterial biofilms, leading to longer
    hospitalization, surgery, and even death.

19
Biofilms and Infections
  • Biofilms are responsible for Otitis Media, the
    most common acute ear infection.
  • Biofilms play a role in Bacterial Endocarditis
    (infection of the inner surface of the heart and
    its valves).
  • Biofilms form frequently in patients with Cystic
    Fibrosis (a chronic disorder resulting in
    increased susceptibility to serious lung
    infections).
  • Biofilms also play a role in Legionnaire's
    disease (an acute respiratory infection resulting
    from the aspiration of clumps of Legionnella
    biofilms detached from air and water
    heating/cooling and distribution systems).

20
Quorum Sensing
  • A process that enables bacteria to communicate
    using secreted signaling molecules called auto
    inducers
  • This process enables a population of bacteria to
    regulate gene expression collectively and
    therefore, control behavior on a community-wide
    scale.

Henke and Bassler, 2004
21
Model of Chronic Pseudomonas aeruginosa
Infection in Cystic Fibrosis
Environmental Pseudomonas
Lung Disease
Bacterial Adaptation
  • Alginate/mucoidy
  • Auxotrophy
  • surface modifications
  • Increased PQS
  • (biofilm, virulence,
  • antibiotic resistance)

Innate Immune Selective Pressure
Increased bacteria - SYMPTOMATIC
PA colonization-ASYMPTOMATIC
22
Behaviors controlled by quorum sensing
  • Structuring of multicellular communities
  • Stress survival
  • Production of
  • Antibiotics
  • Pigments
  • Host tissue degrading enzymes

23
Quorum Sensing can occur ..
  • Cell-cell communication can occur within and
    between bacterial species, and between bacteria
    and their eukaryotic hosts.

24
Quorum Sensing helps in
  • Bacteria use Quorum sensing to mastermind
    behaviors including
  • Mating
  • Releasing toxins
  • Causing disease (virulence )

25
How pathogenic Bacteria Use Quorum Sensing
  • These changes culminate in an infection that can
    ambush and overwhelm our immune system defenses.

The bacteria appear relatively innocuous as they
quietly grow in number.
  • When their population reaches a certain level,
    instant changes occur in their
  • Behavior
  • Appearance
  • Metabolism

26
Quorum Sensing Systems Gram negative bacteria
  • Lux I/R systems
  • Auto inducers acylated homoserine lactone
  • Lux I-type enzymes synthesize acylated homoserine
    lactone (AHL) auto inducers by ligating a
    specific acyl moiety to the homocysteine moiety
    of S-adenosylmethionine (SAM)
  • LuxR-type proteins bind their cognate
    autoinducers and control transcription of target
    genes.

27
Quorum Sensing Systems Gram positive bacteria
  • Two-component systems involved
  • Autoinducers modified oligopeptides
  • The signals are synthesized as precursor
    peptides, which are subsequently processed and
    secreted
  • Sensor histidine kinases detect the extracellular
    peptide autoinducers, autophosphorylate and
    transmit sensory information via phosphorylation
    of a response regulator
  • Response regulator changes gene expression

28
The Chain of Command in Bacterial Communication
29
Quorum Sensing in P. Aeruginosa
Quorum Sensing The ability of a bacterial
colony to sense its size and regulate its
activity in response.
Examples P. aeruginosa
P. Aeruginosa
  • Major cause of hospital infection in the US.
  • Major cause of deaths in intubated CF patients,
    and IV fed patients.

P. Aeruginosa in planktonic (non-colonized) form
are non-toxic, but as a biofilm, they are highly
toxic and well protected by the polymer gel in
which they reside. However, they do not become
toxic or begin to form polymer gel until the
colony is of sufficient size to overwhelm the
immune system. Before this, they cannot be
detected by the immune system.
30
Quorum sensing in P. Aeruginosa
Planktonic
Loosely Bound
EPS secreting
31
Wall Sensing in P. Aeruginosa
Wall Sensing The ability of bacteria to
differentiate in response to Contact with a wall
(the substratum).
EPS secreting
Planktonic
Loosely Bound
32
Intraspecies vs. interspecies communications
  • AHL type autoinducers are for intraspecies
    communications
  • AI-2 and its synthase, LuxS, are widespread,
    existing in many bacterial phyla. AI-2 is
    suggested to serve as an interspecies bacterial
    communication signal.

33
How quorum sensing works? Signaling compounds,
auto inducers AI synthases (luxI gene
products) cell density indicators -
non-essential aa, acyl homoserine lactones
lactone ring part - binding to a receptor site
acyl chain tail determining the species
specificity - oligopeptides -
diketopiperazines - quinolone - furanones
Recognition systems LuxR transcriptional
regulator specific binding sites for AHL and DNA
(sensor/transducer) Genetic basis regulatory
circuit involving both regulatory genes
accumulation of AHL - activating gene
transcription
34
Laboratory made molecules have solutions to
counter quorum sensing
Autoinducer 2 may hold the key to disrupting
quorum-sensing.
  • AI-2 contains the element boron

AI-2 and similar boron-containing molecules made
in the laboratory could serve as decoys to
subvert virulence and other quorum-sensing
behaviors
35
The three general classes of quorum-sensing
systems
36
Communication Between Prokaryotes and Eukaryotes
  • Chemical communication extends to the eukaryotic
    hosts with which bacteria engage in pathogenic
    and symbiotic relationships.
  • P. aeruginosa AHLs enter eukaryotic cells and
    stimulate production of chemokine interleukin 8
    (IL-8), which in turn induces the NF-kB
    transcription factor.
  • These responses cause recruitment of neutrophils
    to the lung, in which they contribute to
    pulmonary inflammation and tissue deterioration.

37
Need for Inhibition of quorum sensing
  • Inhibition of quorum sensing has been proved to
    be very potent method
  • for bacterial virulence inhibition.
  • Several QS inhibitors molecules has been
    discovered.
  • QS inhibitors have been synthesized and have
    been isolated from several
  • natural extracts such as garlic extract.
  • QS inhibitors have shown to be potent virulence
    inhibitor both in in-vitro
  • and in-vivo, using infection animal models.

38
What is the need for Quorum sensing inhibitors ?
39
Strategies for quorum sensing inhibition
3 strategies can be applied
Targeting AHL signal dissemination
Targeting the signal receptor
Targeting signal generation
Signal precursor
Signal precursor
Signal precursor
X
Signal
Signal
Signal
X
X
Signal receptor
Signal receptor
Signal receptor
40
Further research is needed in sociomicrobiology
on .
  • Further studies are needed on quorum sensing
  • regulated gene expression
  • Onset of QS
  • Affects on Onset
  • Architecture and physical flow
  • Functional consequences on biofilm
  • community
  • Role in mixed species systems
  • Effects of signal consumption

41
Visit me for more topics of interest in
infectious diseases
42
  • Created by Dr.T.V.Rao MD for e learning
    resources for Medical Microbiologists in the
    Developing world
  • Email.
  • doctortvrao_at_gmail.com
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