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Molecular Mechanisms of Microbial Pathogenesis and Virulence. Controlling Infectious Diseases The pre-antibiotic Era- Improving Sanitation & hygiene education Typhoid ( Salmonella ), Plague ( Yersina pestis ) Syphilis ( Treponema pallidum )
Air conditioners and Legionella
3. Removing and / or substituting environments:
SARS, HIV, Lyme disease
4. Aging population, compromised immunity
1. Physiological Adaptation – Quorum sensing
2. Genetic Adaptation
Acquiring new genes - Genetic
Trojan Horse: quorum sensing
Various stages of bacteria eucaryote cell interaction during infection
Pathogenic microbes subvert functions of hosts in many ways:Host signaling, host-parasite signaling; parasite signaling
Acquiring New Genes- Horizontal Gene Transfer & Genetic Recombination
Mitochondria – Classic evidence for lateral gene transfer and genome miniaturization?
Mitochondria genesis and function is a product of both the mitochondria and nuclear–encoded genes. Consequently, a mechanism for the coordination of transcription must exist. Is this under mitochondrial (prokaryotic) control
The Human Mitochondria genome database at the URL http://www.mitomap.org/
M. peumoniae genome is 816kb (an additional 209 ORFs). How did this difference occur in the same genus? http://www.zmbh.uni-heidelberg.de/M_pneumoniae/genome/G_Comparison.html Gene transfer, of course!!!
Microbial Gene Transfer: How are genes transferred? What are the consequences?
Cell Biologists interpretation: Transformed cell lines means immortalized cells. This can occur by DNA mutation or by gene transfer mechanisms
Microbiologists interpretation: Transformation is one the 3 methods of gene transfer
Don’t learn transformation in isolation. Make connects with the knowledge you already have on cell membranes
Cell to cell contact between a donor and a recipient cell in which genes are transferred.
Conjugation process requires different proteins- one protein forms a bridge between the two cells (pili) and another is required for transfer of the gene. The genes are located on plasmids.
3. Cell to cell transfer of plasmids by conjugation
Conjugation plasmids encode (i) mating pair functions and (ii) DNA transfer (transmissibility) and replication.
Two types of types of plasmids are known: (i) self –transmissible and (ii) conjugative transposons
Self-transmissible Plasmids: Large >30kb plasmids.Can transfer themselves (F+); mobilisable plasmids: Unable to transfer themselves as they lack the ability to form a mating bridge (F-)
Conjugative Transposons: Integrate into host chromosome. It can mobilise the transfer of the chromosomal DNA from one cell to another. Strains that transfer high large amounts of chromosomal DNA during conjugation are called high frequency recombinants (Hfr)
Insertion sequences (IS) assist in the integration of transposons (Tn) into homologus sites of recipients genome. Different Hfr strains are produced as a result
Genes for conjugative transfer
Replication & segregation genes of F plasmid
99kb F (Fertility) Plasmid Genetic Map (E. coli)
Origin of transfer
4. Types of plasmids & their biological significance
Remember- essential host functions not part of plasmid genes
Pseudomonas- entire metabolic degradation pathways of unique compounds – camphor, napthalene.
Cryptic plasmids – we know little of the plasmid functions
5. Resistance Plasmids (R plasmids)
R100 carries resistance for sulfonamdes, tetracyline, chloramphenicol, spectinomycin, mercury. Broad enteric host range- Escherichia, Proteus, Klebsiella, Salmonella, Shigella,
Bacterocins inhibit or kill related species or different strains of the same species (limited inhibitory spectrum to antibiotics)
E. coli plasmids- Col
Mobilised via plasmids.
Promote changes to the host DNA- Rearrange and or delete genes
Integrons are IS elements or transposons which create and move large gene clusters as a single unit - PAI