Bacterial Survival Mechanisms and Pathogensis

role of bacterial cell envelope

modulates bacterial interactions with their environment

effect of secreted proteins from mutualistic and pathogenic associations

•  modify host physiology → necessary for bacterial survival → e.g. promote colonization of host (toxins and effector proteins)

what are secretion systems

• Protein export machinery outside the cells & into other cells.

• Difference in export depending on Gram -positive or –negative bacteria

features of SEC

• general secretion

  • Ubiquitous and essential

  • Main route and protein of export

  • Requires signal peptide leader sequence

features of TAT

•  twin arginine translocation

  • Not as widespread

  • Normally transports fewer substrates than Sec system

how many layers of lipids in gram negative cell wall

2

how does cholera cause diarrhoea

• Cholera toxin (CTX) --> binds to GM1 ganglioside receptor

•  CTX endocytosed and trafficked to EPR

• Activates adenyl cyclase system, increasing cAMP levels

• cAMP triggers inhibition of reabsorption of Na+/K ions and hypersecretion of chloride ions

• Osmotic gradient causes movement of H2O into intestinal lumen --> diarrhoea

 

features of T1SS

• Double membrane spanning export system

• Translocate substrates in one step across 2 membranes

• Virulence factors such as metalloproteases, adhesion proteins

• Uropathogenic strains of E.coli

function of T3SS

•  deliver effector proteins across the bacterial & host membranes into the cytosol of host cells

•  Modulate a large variety of host cell functions (including immune & defence responses)

Regulation of T3SS gene expression

• TTSS contains >20 proteins

• gene expression coupled to secretion

• signals, regulators and networks vary from one system to another

Salmonella typhimurium is …

gram negative

T3SS-1

• Early phase invasion of enterocytes and M cells

• Activation of pro-inflammatory responses

T3SS - 2

• Later phase of infection

• Intracellular survival and replication within macrophages

 

features of T4SS

• DNA and protein transfer

• Target cells --> animal cells and bacteria

• Gram +/-

• T4SS may need 25 proteins

• Role in pathogenesis

features of T6SS

• Protein transfer

• Targets animal and bacteria

• Role in pathogenesis

• Translocated effector proteins into target cells in one step

• Contractile nanomachine --> one of several protein subcomplexes

what are dynamic firing cycles in T6SS

• expulsion of a cell-puncturing device loaded with multiple toxins

T7SS

• Used by TB

• ATPase driven export

• Major secretion pathway for 200 proteins

• Interactions with host cells and modulation of immune system

• Involved in pathogenesis

• 5 distinct T7SS

role of Tir

 triggers actin polymerisation and pedestal formation underneath attached bacterium

How to distinguish between commensal and pathogenic E. coli?

• Intestinal cells can sense the T3SS present in pathogenic E. coli

• Trigger NF-KB activation in a non-TLR dependent mechanism

• T3SS recognition by the immune response to differentiate between pathogen & commensal

pathogenic

disease causing bacteria, affects all normal host defences

non-pathogenic

 organisms invade an individual without causing any obvious detectable symptoms

commensal

 an organism that is found normally on those parts of the body that are exposed or communicate to the external environment

changes in normal flora -  hormonal physiology and development

• Female genital tract and lactobacilli

changes in normal flora -  antibiotics select for a resistant flora

• Candida overgrowth in mouth/vagina

• C diff - antibiotic associated colitis

changes in normal flora - new organisms

• Neonate from maternal tract during birth

bacteria need…

• iron

• to adhere to host mucosa

adherence in gram positive bacteria

• adherence to host cells e.g pili, fimbriae

• prevents bacteria from being washed off by significant fluid flow

• formation of a microcolony

• relevance to pathogenicity

exotoxin

secreted by a bacterium into the environment

endotoxin

LPS of gram negative bacteria

enterotoxin

• an exotoxin only active in GI tract

iron sequestering

• Iron is essential

• Limiting in host

• Sequestration is critical for in vivo success

• Produce iron binding compounds called siderophores

• Capture from the host

defensive factors - polysaccharides capsule

• negatively charged

  • Slime

  • Biofilm

defensive factors - immunologic mechanisms

• LPS - cytokine stimulation --> septic shock

• Outer membrane proteins