Pathogenesis of bacteria and viruses

Virulence factors
Bacteria

Regulation of virulence factors: two-component systems (TSS)

Schmidl, S., Sheth, R., Wu, A. and Tabor, J. (2014). Refactoring and Optimization of Light-SwitchableEscherichia coliTwo-Component Systems. ACS Synthetic Biology, 3(11), pp.820-831.
A bit of synthetic biology…

Key events of pathogen-host interaction
Colonisation - invasion
Multiplication
Transmission
Damage
Uropathogenic E. coli binding a kidney receptor with adhesins at the top of P-pili

Enteropathogenic E. coli build specialised structures for adhesion

Biofilms

Invasion
“Zipper mechanism”. Listeria invading non-phagocytic cells.
?-catenin
?-catenin

Bonazzi, M. and Cossart, P. (2006). Bacterial entry into cells: A role for the endocytic machinery. FEBS Letters, 580(12), pp.2962-2967.

“Trigger mechanism”. Salmonella.
Type III Secretion System
Transmission EM micrograph of Salmonella possessing T3SS

Cryo-EM micrograph of T3SS
Abbreviations used: OR, outer ring; IR, inner ring; OM, outer membrane; IM, inner membrane. (B) An axial section through the map in (A). (C) Transverse sections through the map in (A) at the level of the neck (top) and IR1 (bottom).
Notti, R. and Stebbins, C. (n.d.). The Structure and Function of Type III Secretion Systems. Virulence Mechanisms of Bacterial Pathogens, Fifth Edition, pp.241-264.

What happens once bacteria are in?

Damage caused by bacteria
Direct – from bacteria action
Indirect – from host response
Cytolysin

AB toxins

Viruses

HIV capsid

Beta-hairpin can adopt alternate conformations that differ by up to 15 Å.
Closed
Open

HIV-1 reverse transcription is inhibited by blockade of the capsid pore
CAhexamer crystal structure in complex with hexacarboxybenzene, which is co-ordinated by R18

Current approach to AIDS treatment
Nucleoside Reverse Transcriptase Inhibitors
Protease Inhibitors
Fusion Inhibitors
Highly Active Antiretroviral Therapy
Non-Nucleoside Reverse Transcriptase Inhibitors

AZT