Bacterial Adaptation and Survival PDF

BACTERIAL ADAPTION AND SURVIVAL Dr Gill Douce [email protected] Lecture Aims: To describe some of the genetic mechanisms by which acquire new genes that can influence their survival How this can enhance influence their capacity to cause disease To discuss how bacteria couple o...

BACTERIAL ADAPTION AND SURVIVAL Dr Gill Douce [email protected] Lecture Aims: To describe some of the genetic mechanisms by which acquire new genes that can influence their survival How this can enhance influence their capacity to cause disease To discuss how bacteria couple of mechanisms bacteria use to sense the environment, and to communicate with each other What drives bacterial genetic change?  Organisms adapt rapidly to changing circumstances and pressures Majority of changes lethal. In nature, all DNA is Mutated clone – subject to change. But if a mutation is dominant….UNTIL Single nucleotide advantageous, and the polymorphisms conditions offer a (SNPs) selection advantage the organism proliferates rapidly Multiplication Rates Humans: 10-12 years puberty, 9 months gestation, 1-2 offspring Bacteria: Logarithmic growth 20-25 min, double population 8h: single clone replicated 108 colonies Evolution - rapid  Mutation Alter efficacy of antibiotic by alteration of target site Alter receptor recognition (of tissue) Alter recognition by the host (immunity) But what about acquisition of genes for specific virulence associated traits: Toxins Adhesins Acquiring new genetic traits in bacteria Known as horizontal genetic transfer Rapid growth ensures spread within population  Horizontal gene transfer Natural Transformation: uptake and incorporation of naked DNA Conjugation: genetic exchange between bacteria Transduction: Exchange occurs as consequence of phage predation Transformation - Occurs in bacteria that are naturally ‘Competent” Occurs when ssDNA is Uptake of DNA and incorporation into released when bacteria die genome of ‘competent’ bacteria through and lyse homologous recombination Only a few bacteria are naturally competent. Probably evolved as a mechanism of natural repair within the community Some become competent in response to quorum sensing compounds – released by bacteria – competency factors But if gene associated with antibiotic resistance – transformed bacteria will now be resistant  Conjugation (bacterial sex) Conjugative plasmids: plasmids encode the genes for pilus formation and the tra genes for transfer Best described F factor in E.coli Initiated by special pilus - protrudes from donor cell F+ve F-ve Plasmid encodes F pilus On cell contact, pilus contracts bringing cells into close proximity DNA transferred by rolling circle replication Plasmid Plasmid encodes F encodes F pilus pilus Relaxasome – molecular structure DNA passes through Strains in which plasmid integrates into chromosome as know as HFr strains: integrate/excise at ‘high frequency of recombination’ Transduction Bacteriophages: predate bacteria Two lifecycles – Lytic – results in replication of bacterial genome and destruction of bacteria  Transduction Bacteriophages: predate bacteria Two lifecycles – Lytic – results in replication of bacterial genome and destruction of bacteria Lysogenic – results in integration of the bacteriophage DNA into the bacterial chromosome Excision can occur when bacteria stressed – reversion to lytic lifestyle  Transfer of DNA between bacteria by Generalised bacteriophage  + + Increased adhesion Toxin production Acquisition of new traits leads to increased virulence Enteroaggregative Enterotoxigenic E.coli and invasive E.coli Increased Increased adhesion adhesion and toxin and production membrane Enterohaemorragic E.coli Enteropathogenic E.coli modification  Integration of new DNA - Pathogenicity islands Insertion of ‘foreign’ DNA inserted into bacterial chromosomes recognised Difference in GC content of DNA Large inserts known as pathogenicity islands Frequently encode virulence associated traits Chromosomal integration/excision DNA introduced may not persist Restriction systems, such as phage encoded CrispR/Cas recognise foreign DNA Endonuclease activity If persist may integrate and multiply within the chromosome Many toxins – cholera toxin, diphtheria toxin (phage encoded)  Capacity to sense and respond Multiple mechanisms for controlling gene regulation Essential due to size cannot afford to waste resource Main types of communication Quorum sensing – results in changes in gene expression as a consequence of signalling at the population level Environmental sensing – results in changes to gene expression within an individual bacterium – two component regulation Symbiotic relationship Aliivibrio fischeri Hawaiian Bobtail Squid Provides selective environment Produces fluorescent light exclusively for A. fischeri Production of light casts a light shadow from the squid Nocturnal - moon above the squid will cause a night Cancels out the moon shadow to be cast by the squid shadow and shields the squid from predators Alerts predators below of presence  QUORUM SENSING/ Bacterial Tweeting Quorum – is defined as a specific/minimum number Quorum sensing Occurs when bacteria sense their population size and coordinating their behaviour in response Behaviour changes depend on the low or high cell bacterial density and the accumulation of autoinducer (AI) proteins  QUORUM SENSING in Aliivibrio fischeri lux operon controls the production of light in A. fischeri. LuxR – produces transcription activator LuxI – synthesises AHL At low High AHL, binds to concentrations, AHL LuxR diffuses out of the Increased cell activation of luxI Increased No light produced expression of lux genes Light produced LuxI – +ve autoregulation  QUORUM SENSING in Vibrio fischeri lux operon controls the production of light in A. fischeri.  QUORUM SENSING Quorum sensing exploited by many bacteria to control the expression of several traits including produce of virulence factors rather than light. Known to influence biofilms formation, virulence, antibiotics agr operon controls P. aeruginosa has two QS systems virulence in S. aureus – las and rhl Environmental sensing and ‘two component signal transduction’ Transmembrane sensor kinase Sensory domain on outside of the cell Kinase domain protrudes into the cytoplasm On detection of a signal – conformational change in kinase domain – results in autophosphorylation Response regulator – Transphosphorylated by the kinase – acts to enhance/ repress gene expression of one or more genes  Goldilocks syndrome – ensuring the right amount EnvZ/OmpR two component system used by pathogens such as Salmonella Lifestyle means exposure to different environments Many nutrients are acquired through non-selective porins found in the membrane OmpF – large pore size OmpC – smaller pore size OmpF: larger pore size, nutritionally more competitive but more susceptible to osmotic shock OmpC: smaller pore size, nutritionally less competitive but less susceptible to osmotic shock Pore size is influenced by bacterial ‘sensing’ Low osmolarity – low constitutive OmpR phosphorylation and preferential expression of OmpF High osmolarity – high OmpR phosphorylation by EnvZ and preferential expression of OmpC  Other examples of two component regulation Influence movement towards or away from a stimulant by modification of flagella rotation CheAW/Y associated with tumbling, which reduces movement away from a nutritional source PhoPQ sensing low Mg+ ions found within phagolysosomal vacuole following macrophage Enhances virulence by stimulating expression of traits in Salmonella that enhance intracellular survival  The power of transcriptomics Understanding adaption to different environmental niches through recovery and sequencing of mRNA from bacteria recovered from different environmental niches Would expect increase in genes that required for survival within a specific niche Linked to an increased in mRNA transcripts for those genes Using comparative transcriptomics mRNA recovered from bacteria grown conventionally Number of transcripts Sequencing mRNA recovered from of nucleic mapped to the genome bacteria recovered from acid infected cell in vitro allows identification off genes both up and down regulated – global understanding of bacterial adaption In this lecture Highlighted how natural mutation influences bacterial evolution Described mechanisms associated with the acquisition of new genetic traits and described how this can influence virulence Discussed how bacteria sense and respond to environmental change. All of which contribute to their amazing capacity to colonise our planet If you don’t like bacteria – you really need to find yourself another planet Eden Project