Bacterial Pathogenesis and Virulence Part 1

Question 1

define pathogenesis

Answer 1

all of the biological steps that lead to the development of a disease (from exposure to development of symptoms)

Question 2

define virulence

Answer 2

a quaNtitative term referring to the degree of disease-causing capability of an agent

Question 3

define virulence determinant/factor

Answer 3

structures expressed or properties or strategies utilized by organisms that enable them to cause disease

Question 4

outline the steps leading to bacterial disease (5)

Answer 4

1. bacterial overcome mechanical clearance via adherence to host surfaces, production of biofilms, and/or invasion of host cells (this determines where they colonize later)
2. at the same time they are overcoming mechanical barriers, bacteria also evade clearance by the immune system via antigenic variation, survival within professional phagocytic cells, and resisting complement-mediated killing
3. once they do the above, bacteria acquire nutrients to support growth via receptors for host iron binding proteins and siderophores
4. bacteria colonize tissues
5. bacteria inflict damage to host tissues where pathogenic bacteria produce toxins and/or elicit immune responses causing damage; resulting in the clinical manifestations of disease

Question 5

what do bacteria have to overcome to adhere to host surfaces?

Answer 5

the main obstacle to adherence is the repulsive forces created by negative surface charges of bacteria and host cells, but bacteria express adherins (binding entities) that bind to specific receptors on host surfaces to overcome that electrostatic repulsion

Question 6

what is an adhesin?what are the 3 types of adhesin-receptor interactions?

Answer 6

there are two requirements for adherence of bacteria to a host cell surface:
1. adhesin: binding site on bactera
2. receptor for adhesin on host cell curface

3 types of adhesin-receptor interactions

1. lectin-carbohydrate interactions: lectins are proteins/glycoproteins that bind to carbohydrates; this is the largest group of adhesion-receptor interactions
2. protein-protein interactions
3. hydrophobic region-lipid interactions: hydrophobic region of protein adhesin interacts with lipids

Question 7

list and describe the 3 types of bacterial adhesins

Answer 7

1. pilus: very long hair-like structure that extends from the surface of many bacteria made from small identical protein subunits that form a cable-like appendage, with the cable capped by a unique adhesin that interacts with the host
2. fibrillar surface proteins (fimbriae): long, complex, and variable multidomain proteins attached to the bacterial surface composed of at least one adhesive domain and a “stalk” domain where the stalk region serves to project the adhesive domain from the bacterial surface; shorter than pili but still from a distance
3. integral membrane proteins: different in structure from pilus or fimbriae; are anchored in bacterial cell membrane and have SHORT exposed residues that can interact with host receptor (intimate contact)

combination of adhesion/receptor interactions helps determine tissue tropism (where bacteria is found in the host)

Question 7

why do bacteria invade host cells? (3)

Answer 7

1. stealth: to hide from immune system
2. nutritional bounty: host cytosolic concentration of metals, amino acids, and sugars is higher and more reliable than in the environment
3. host cells serve as a means of crossing physical barriers and dissemination, allowing bacteria to move through epithelial or endothelial cells to access underlying tissue

Question 8

explain the mechanisms used by bacteria to invade host cells

Answer 8

1. bacteria initiated cell entry occurs in non-professional phagocytes (epithelial and endothelial cells) via a unique set of invasion proteins in the bacteria and involves rearrangement of host cell actin cytoskeleton
2. two types of entry:
   2a. zipper mechanism: bacterial protein (invasion factor) binding to host cell receptor results in host cell signaling events that form an “invagination cup” and induce the cell to engulf the bacteria where the actin filament rearrangement resembles two sides of an open zipper flanking the bacteria
   2b. trigger mechanism: utilizes multiple proteins to allow bacteria to assemble a hollow needle/injectisome complex which docks its tip in the host cel membrane and injects the bacterial proteins (effectors) into the cytosol of the host cell; the effectors then disrupt the eukaryotic signaling pathway and rearrange the actin to form pseudopod extensions that fuse to engulf the bacteria

Question 9

what are the 5 functions of biofilms?

Answer 9

1. protect against harsh environments like extreme temps, UV light, dessication, immune system assault, or shear forces generated by blood or urine flow
2. provides a means of communication between bacteria (quorum sensing)
3. provide close proximity for exchange of genetic material
4. increase protection for bacteria in interior even if bacteria near periphery may die
5. antibiotic and antibody penetration is reduced