Pseudomonas aeruginosa is a Gram-negative bacterium that causes severe, and ofte

Question

Pseudomonas aeruginosa is a Gram-negative bacterium that causes severe, and often life-threating infections in immunocompromised individuals. In these susceptible individuals, P. aeruginosa can establish infections in a wide range of tissues, including the lung, GI tract, eye, ear, urinary tract, skin, and blood. P. aeruginosa is common in the environment and is found of the skin of approximately 5% of healthy individuals. It is also other found on hospital equipment, such as ventilators and catheters. As a consequence, P. aeruginosa accounts for ~10% of hospital-acquired infections. To study the role of complement in response to P. aeruginosa infections, the following studies were performed in mice. Wild-type mice and mice deficient in either C3 or C5 (C3 -/- or C5-/-, respectively, were infected with equal amounts of P. aeruginosa and were monitored for 72 hours. The data from these studies are shown in the graphs of survival, below. Genetic data from studies of human data also indicate that individuals with genetic deficiencies in one of their collectins, or ficolins, show increased susceptibility to P. aeruginosa infections.

a). What do the data suggest about the contribution of complement in protection against P. aeruginosa infections? Explain your reasoning.

b). What do the data suggest about which complement pathway is most likely activated by P. aeruginosa infections? Explain your reasoning.

c). Based on the role of C5 in complement, provide two possible explanations for why P. aeruginosa infections are so severe in C5-/- mice.

Explanation / Answer

A. Complementation mechanism plays a major role in attacking Gram negative bacteria. Membrane attack complex (MAC) is formed on the bacterial membrane and makes a pore on the membrane. So bacteria not able to maintain the ionic balance, totally collapse and died. Thats why wild type mice has a high survial rate compare to mutant mice.

B. Classical pathway - This pathway is activated by Ig G and Ig M. After infection by any micro organisms it take some time to activate the immune system of the body. It cleary shows after 20 hours incubation only both C3-/- and C5-/- mice are started to decrease in number. Wild type also there is decrease in number but after some period of time it becomes stable it is due to activation of immume system and increase in the antibody like IgM and IgG.

C. C5 is the first step of the lytic part of the complement pathways. The C5b is the first component of the self-assembly of Membrane Attack Complex (MAC) it leads to destructiion of microbes. All the three pathways in complement system finally joins here and makes a MAC comples. That why it is important in the complement system.

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