9/15/2016 Bacteria acquire genes to become Food pathogens Horizontal transfer of blocks AN INTRODUCTION of virulence genes from a common microbial ancestor Bacterial Virulence leads to. brief overview Different pathogens use common strategies to cause infection and disease Emergence of new pathogens hgR金带Kal R.Mathew that are often resistant to multiple antibiotics Common strategies Adherence to host surfaces of pathogenicity the importance of first impressionis agents .Surfaces include skin,mucous membranes,deeper fissues prevention Adhesins prevent bacteria New effort is on from being washed away by or li mechanical forces produced by the host ance eria als
9/15/2016 1 Bacterial Virulence brief overview Bacteria acquire genes to become pathogens Horizontal transfer of blocks of virulence genes from a common microbial ancestor leads to…… • Different pathogens use common strategies to cause infection and disease • Emergence of new pathogens that are often resistant to multiple antibiotics Common strategies of pathogenicity • A thorough understanding is esesntial to develop better, novel vaccines and therapeutic agents for treatment and prevention • New effort is on identifying drugs that target virulence activities of pathogens instead of preventing their growth Adherence to host surfaces the importance of first impressions • Key step in host-pathogen interaction • Surfaces include skin, mucous membranes, deeper tissues • Adhesins prevent bacteria from being washed away by mechanical forces produced by the host • Biofilms are a common mechanism of adherance • Commensal bacteria also adhere to colonize the host
9/15/2016 Adhesins Invasion A bacterial surface protein induces endocytosis. Proteins Carbohydrates In the cell,some escape and others ‘6R865P8Esor comporents of cell wall multiply in the phagosome. cell membrane or capsule ‘ Bacteria inject proteins into the host cell causing cytoskelet al r engulfment of the bacteria. In the cytosol,bacteria lyse the vacuolar membrane,escape Escherichia coli P fimbrioe and move about in the host Cy十0s0. brush border ville brush border villi Invasion Evasion of host immunity Salmone/la bacteria produce invasins,proteins that cause the actin of the host cell's IgA proteases cytoskeleton to form a basket that carries the bacteria into the cell ilopodia assembly cannot protec 2
9/15/2016 2 Adhesins Proteins • Lipoproteins or glycoproteins • Often associated with fimbriae Carbohydrates • components of cell wall • cell membrane or capsule Vibrio cholerae rabbit intestinal brush border villi Escherichia coli calf intestinal brush border villi No capsule Capsule Escherichia coli P fimbriae Invasion Bacteria inject proteins into the host cell causing cytoskeletal reorganization and engulfment of the bacteria. In the cytosol, bacteria lyse the vacuolar membrane, escape, and move about in the host cytosol. A bacterial surface protein induces endocytosis. In the cell, some escape and others multiply in the phagosome. Invasion • Salmonella bacteria produce invasins, proteins that cause the actin of the host cell’s cytoskeleton to form a basket that carries the bacteria into the cell Evasion of host immunity IgA proteases
9/15/2016 Evasion of host immunity Evasion of host immunity Immunoglobulin-binding proteins Resist complement and protein A of 5.Aureus opsonisation helps inhibit phagocytic engulfment capsule,LPS,surface proteins acTs as an immunological disquise c1 complex Complement system:part of the immune system that enhances (complements)the ability of antibodie and phagocytic cells to clear microbes and damaged cells from an organism,promotes inflammation,and attacks membrane Evasion of host immunity Evasion of host immunity ·Antigenic mimicry .Antigenic or phase variation vary the structure of surface components ·Adopt a cryptic niche inside phagcytes or a biofilm mece
9/15/2016 3 Evasion of host immunity Immunoglobulin-binding proteins protein A of S. Aureus helps inhibit phagocytic engulfment acts as an immunological disguise Evasion of host immunity Resist complement and opsonisation capsule, LPS, surface proteins Complement system: part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promotes inflammation, and attacks membrane Evasion of host immunity Evasion of host immunity • Antigenic mimicry • Antigenic or phase variation vary the structure of surface components • Adopt a cryptic niche inside phagcytes or a biofilm
9/15/2016 Damage to host cells Toxin production is an adaptive mechanism that improves interaction with the host and often has a negative impact on the host Protein toxins are enzymes delivered into host cells,directly by a secretion system or indirectly from the environment Toxins inhibit a host cell function or ore forming toxins kills the host cell Proteolytic toxins A-B subunit toxins Damage to host cells Damage to host cells Non-Protein Toxins acquiring nutrients from the host Septic shock occurs Siderophores-proteins that bacteria when sepsis(organ injury or damage in respo nse to secrete to get iron bound by host proteins ifec6Neaste dangerously low blood pressure and abnormalities in cellular metabolism NH Cell wall components (CO-CH-CH2-0) LPS Direct Damage-Host cells can be destroyed peptidoglycan due to pathogens proliferating inside host teichoic acids tissues 4
9/15/2016 4 Damage to host cells • Toxin production is an adaptive mechanism that improves interaction with the host and often has a negative impact on the host • Protein toxins are enzymes delivered into host cells, directly by a secretion system or indirectly from the environment • Toxins inhibit a host cell function or kills the host cell Pore forming toxins Proteolytic toxins A-B subunit toxins Cell wall components LPS peptidoglycan teichoic acids Non-Protein Toxins Septic shock occurs when sepsis (organ injury or damage in response to infection) leads to dangerously low blood pressure and abnormalities in cellular metabolism Damage to host cells Damage to host cells • Siderophores - proteins that bacteria secrete to get iron bound by host proteins • Direct Damage- Host cells can be destroyed due to pathogens proliferating inside host tissues
9/15/2016 Multi-dimensional View of Pathogenicity ·ex acquire genes,evolve ·Sense portal of entry ·Switch gene regulation ·Swim find a tissue to colonize. penetrate mucus ·Stick prevent removal from tissues Scavenge siderophores-iron nutrients Survive oxidatative-phagocytes,acid- stress stomach,heat-fever Multi-dimensional View of Pathogenicity ·Stealth avoid the immune system Strike back damage host tissues Subvert alter cytoskeleton and cell signaling,prevent phagocytosis or induce uptake ·Spread find other tissues Scatter exit the host and find another host-evolve 5
9/15/2016 5 Multi-dimensional View of Pathogenicity • Sex acquire genes, evolve • Sense portal of entry • Switch gene regulation • Swim find a tissue to colonize, penetrate mucus • Stick prevent removal from tissues • Scavenge siderophores-iron nutrients • Survive oxidatative-phagocytes, acidstress stomach, heat-fever Multi-dimensional View of Pathogenicity • Stealth avoid the immune system • Strike back damage host tissues • Subvert alter cytoskeleton and cell signaling, prevent phagocytosis or induce uptake • Spread find other tissues • Scatter exit the host and find another host- evolve
