Social Behaviour in Bacteria

Social Behaviour •A behaviour is social if it has consequences for both the actor and the recipient. •Social behaviours can be categorized according t...

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Social Behaviour in Bacteria

Dipankar Chatterji, Molecular Biophysics Unit, Indian Institute of Science, Bangalore ([email protected])

Social from Latin socialis -‘allied’, from socius -‘friend’.

Social Animals

Images taken from google images

Social Insects

Social Humans

Image taken from google images

Bacteria • • • •

Prokaryote Unicellular Good & Bad Division through binary fission

Scanning Electron Micrograph of Escherichia coli. Image taken from google images

Bacteria & Social? What is the need for asexual unicellular organisms to display social behaviours

Herbert Spencer •Contemporary of Darwin •Known for ‘ survival of fittest’ •Popularized ‘Altruism’ •First to apply term ‘altruism’ to single celled organism


Bacteria are indeed social! Image taken from

Peter Kropotkin • Russian geographer, economist, activist, philologist, zoologist, evolutionary theorist, philosopher

( 1842-1921)

Image taken from

• “…we must be prepared to learn some day, from the students of microscopical pondlife, facts of unconscious mutual support, even from the life of microorganisms.” Kropotkin (1902)

Social behaviour of microorganisms was hardly explored

By the end of last century, the studies on the social behaviour of microorganisms bloomed

Social Behaviour • A behaviour is social if it has consequences for both the actor and the recipient. • Social behaviours can be categorized according to the fitness consequences they entail for the actor and recipient.

Classification of social behaviour

Foster KR, Social behaviour: genes, ecology and evolution

Secreted products used for social behaviour in bacteria • Enzymes • Extracellular substances

• Siderophores • Autoinducers

Siderophores: Iron carriers

Faraldo-Gómez & Sansom, Nature Rev. Mol. Cell Biol. 4: 105 (2014)

Selfishness or cheating • Tragedy of commons • Pseudomanas aeruginosa form biofilms in the lungs of cystic fibrosis patients and secrete siderophores (iron carriers vesicles) to maintain infection • It is found that some cells do not secrete siderophores • This reduces the overall virulence • Hence, selfishness is bad in the long run Foster KR, Social behaviour: genes, ecology and evolution

Tragedy of commons

Mutual benefit or Mutualism

• The host: the termite Mastotermes darwiniensis •A symbiont Mixotricha paradoxa that helps to break down cellulose. The “fur” on the surface is actually the flagella of symbiotic spirochete bacteria that helps it to swim around Konig et al, Symbiosis 44:1 (2007)

Altruism: mazEF toxin- antitoxin system of Escherichia coli



mazF Infected cells die

Phage infection

During normal growth, toxin bound to antitoxin

Phage infection causes destruction of less stable antitoxin leading to release of the toxin, which kills the Hazan & Engelberg-Kulka, Mol. Genet. & infected cells and saves the uninfected population Genomics 272:227 2004

Spread of antibiotic resistance



Sensitive population with very few resistant mutant

Enrichment of resistant mutants

Entire population becomes resistant

 Antibiotic resistance is a phenotype acquired by bacteria during prolonged treatment due to selection pressure.

 Attributed by several factors like mutations in the

antibiotic binding site or due to other physiological changes .

Time line of antibiotic resistance

Anne E Clatworthy, Emily Pierson & Deborah T Hung. Nature Chemical Biology 3, 541 - 548 (2007)

“A post-antibiotic era—in which common infections and minor injuries can kill—far from being an apocalyptic fantasy, is instead a very real possibility for the 21st Century.” Beatson and Walker (2014) Tracking antibiotic resistance. Science,1454-1455.

Altruistic defense Sub-lethal antibiotics

Sub-lethal antibiotics

Slow growth

Slow growth

•The process repeated ten times with increasing concentration of antibiotics. • Most of the cells were antibiotic sensitive, only very few cells were antibiotic resistant •These highly resistant isolates produce the signalling molecule indole, which activates drug efflux pumps and other protective mechanisms in susceptible kin. •This altruism allows weaker constituents to survive and to have the chance of beneficial mutation.

Lee et al, Nature 467: 82 (2010)

Spite • Bacteriocins are antimicrobial toxins produced by bacteria that target closely related strains and species, and to which the strain is immune. • Photorhabdus asymbiotica (asy) and Xenorhabdus nematophilus (X3) two are bacteriocin-producing, insect-killing bacteria and independently they elicit higher mortality in the host. • When both the bacteria happen to infect the host caterpillar Galleria mellonella, the mortality of caterpillar is reduced Massey et al, Proc. Royal Soc. B 271:785 (2004)

In-vivo and In-vitro proofs of spite

Massey et al, Proc. Royal Soc. B 271:785 (2004)

Cannibalism in Bacillus Active SpoOA cell

Inactive SpoOA cell



Skf- Sporulation killing factor Sdf-Sporulation delay factor

Gonzàlez-Pastor et al, Science 301: 501 (2003)

• Sporulation is an energy-

intensive process that is irreversible after the early stages. • If food resources become available during later stages, sporulating cells would be at a disadvantage relative to bacteria that could initiate growth immediately. • For the bacterial population as a whole, it is beneficial to delay the onset of sporulation.

Rhizobiome: the microbes around the roots of the plant • Studies have shown that there are up to 10 billion bacterial cells per gram of soil in and around plant roots, a region known as the rhizosphere. • Dozens of species appear to suppress plant disease by excreting substances that ward off pathogenic microbes or occupying niches otherwise taken up by the pathogens. • The rhizobiome depends heavily on the soil type. de Vrieze, Science 349: 680 (2015)

Nitrogen Fixation by Legumes The Littlest Farmhands • Biological nitrogen fixation is the process that changes inert N2 into biologically useful NH3. • This process is mediated in nature only by N-fixing rhizobia bacteria (Rhizobiaceae, α-Proteobacteria) • In legumes and a few other plants, the bacteria live in small growths on the roots called nodules. • Within these nodules, nitrogen fixation is done by the bacteria, and the NH3 they produce is absorbed by the plant. • Nitrogen fixation by legumes is a partnership between a bacterium and a plant. de Vrieze, Science 349: 680 (2015)

Gut Microbiome • It helps the body to digest certain foods that the stomach and small intestine have not been able to digest. • It helps with the production of some vitamins (B and K). • It helps us combat aggressions from other microorganisms, maintaining the wholeness of the intestinal mucosa. • It plays an important role in the immune system, performing a barrier effect. • A healthy and balanced gut microbiota is key to ensure proper digestive function.

• Competition for Resources • Restaurant Hypothesis

• Invading Pathogens must compete with resident microbiota to enter into a restaurant or they will be eliminated • Microbes (ASM) aug.2015

Food for thought

No. of human cells: 1013 No. of bacteria on humans: 1014 Zhao L, Nat. Rev. Microbiol. 11: 639 (2013)

No. of human genes: 30, 000 No. of bacterial genes in human 30,00,000

Quorum Sensing • Microbes also display an impressive ability to detect the density of their own and other species through “quorum sensing”. • Quorum : A gathering of the minimal number of members of an organization to conduct business • Quorum Sensing: sensing who is around • It involves a wide variety of secreted compounds known as autoinducers, including some packaged in vesicles • If cells secrete a chemical, then as cell density goes up, so will the local concentration of the chemical. By responding to the chemical, therefore, the cells can respond to their own density. Fuqua et al, J Bacteriol 176: 269 (1994)

Biofilm formation is a developmental process in which bacteria undergo a regulated lifestyle switch from a nomadic unicellular state to a sedentary multicellular state . Biofilm formation by non-motile bacterium

Biofilm formation by motile bacterium

Lemon et al, Curr Top Microbiol Immunol, 322:1 (2008)

Autoinducers: molecules used for intraand interspecies communication

Camilli & Bassler, Science 311:1113(2006)

Biofilms: a city of microbes • Biofilm is a structured community of bacteria embedded in self-produced polymeric matrix and attached to abiotic or living surface. • Biofilms can be composed of multiple species or single. • Biofilms protect bacteria from antibiotics and other environmental insults. They are cause of nosocomial infections as well as persistent infections.

R. Mathew, R. Mukherjee, R. Balachandar and D. Chatterji Microbiology ; 152: 1741-1750


Mycobacterium smegmatis Mc2155 biofilm grown at the air–water interface in a plastic Petri dish.

Altruism in bacteria • Biofilms: City of microbes held together by a series of extracellular substances such as cellulose and adhesins • For instance, dental biofilms • They are everywhere • Antibiotic treatment is not effective • Some die for the good of others and the remaining one grows back Mycobacterium smegmatis biofilm: Gupta and Chatterji (2015)


Mycobacterium smegmatis biofilm

Dental biofilm: a multispecies biofilm Image taken from google images

D-amino acids trigger biofilm disassembly • Compounds that could disrupt and disassemble biofilms can be used as therapeutics. • Richard Losick’ s group reported that a mixture of D-amino acids comprising D-leucine, Dmethionine, D-tyrosine, and D-tryptophan that could act at nanomolar concentrations and trigger biofilm disassembly. • Same group reported that D-amino acids indirectly inhibit biofilm formation in Bacillus subtilis by interfering with protein synthesis. Kolodkin-Gal et al, Science 328: 5978 (2010)

Leiman et al, J Bacteriol 195: 5391 (2003)


Hengge R, Nat. Rev. Microbiol. 7: 263 (2009)

Formation of biofilm leads to the antibiotics tolerance because antibiotics fail to penetrate biofilm matrix to reach bacteria. It is often regulated by quorum sensing phenomenon (cell to cell communication). (Høiby et al., 2010, IJAA)

Persistence in bacteria – A bet-hedging strategy Normal population

Responsive switching (Environmental stress)

Stochastic switching (spontaneous)

Persister formation

Biphasic killing of M. tuberculosis in mice by antibiotics

Slow growth – a sacrifice for survival of the subpopulation under stress conditions

Dhar, N. and McKinney, J.,D. Curr Opinion Micriobiol. (2007)

Stringent response- A social behavior in bacteria Stress and starvation

Normal cell

Persister cell




Growth arrest

Biofilm formation

Antibiotic tolerance

Toxin-antitoxin modules activation


Gupta, K.R. and Chatterji,D. Appl Environ Microbiol. (2015); Maisonneuve, E., et al. Cell (2013).

Stringent Response in Bacteria Environmental stress

Nutrient starvation (Amino acid, Carbon, Fatty acid, Iron, Phosphorous)

(UV, Salt, Acid, Alkali, Heat, Cold, Osmolar, Antibiotics)

STRINGENT RESPONSE Macromolecular Degradation

Reduction to a minimal unit

Macromolecular Biosynthesis

• Fatty acid breakdown

• tRNA and rRNA synthesis

• Proteolysis

• DNA replication

• Amino acid biosynthesis

• Cell division

Key Players:

Rel, (p)ppGpp & RNA polymerase

‘Magic Spots’ MS-I : ppGpp MS-II : pppGpp

Cashel and Gallant (1969) Artsimovich et al., (2004)

Magnusson et al., (2005)

Stringent Response in Mycobacteria Mycobacterium smegmatis mc2155 Ojha A. K., and Chatterji D. (2000, 2001)


(MSMEG_2965; 797 aa)




Catalytic domains





Regulatory domains

• Reciprocal regulation of synthesis and hydrolysis activity S. equisimilis - Hogg et al., (2004)

• Regulation of NTD catalytic activity by CTD in RelMsm Jain et al., (2006, 2007)


Known nucleotide based second messengers in bacteria cAMP (1957)

(p)ppGpp (1969)

Bharati BK & Chatterji D (2013) Gene ; Sharma, I.,Petchiapan A.,& Chatterji ,D (2014) IUBMB Life

cGMP (1974)


Cyclic- di-guanosine monophosphate (c-di-GMP)

 Discovered by Benziman and co workers in 1987 in Gluconacetobacter xylinus [Ross et al (1987) Nature].


(p)ppGpp (+12)

cGMP (+5)




c-di-GMP (+13)


c-di-AMP (+21)


c-AMP-GMP (+4)


Kuldeep Gupta

Anushya Petchiappan