Kinetics and Molecular Requirements of Klebsiella Pneumoniae-Induced Endovascular Infections under Hydrodynamic Shear as a Function of Platelet Activation

Bhalla, P (2014) Kinetics and Molecular Requirements of Klebsiella Pneumoniae-Induced Endovascular Infections under Hydrodynamic Shear as a Function of Platelet Activation. Masters thesis, Indian Institute of Technology, Hyderabad.

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Abstract

Bio-adhesion between invading bacterial pathogens and host cells such as platelets is known to play a key role in the initiation and propagation of bacterial bloodstream infections. The formation of platelet-bacteria heterotypic aggregates allows bacterial cells to evade the innate immune response. Shear forces associated with flowing blood in the human vasculature are known to modulate associations between an invading bacterial pathogen and host cells such as platelets, erythrocytes, and neutrophils. Moreover, blood flow assists hematogenous spread of bacterial infections, and contributes to their severity. This study was undertaken to investigate the effects of shear rate (0-5000 s-1), and shear exposure time (60-120 s) on Klebsiella pneumoniae-platelet heterotypic aggregation. Besides, the effect of thrombin mediated activation of platelets upon heterotypic aggregation was studied by treating the platelets with different thrombin concentration. Also, different platelets to bacteria ratios were tested for the selection of the ratio that best resulted in increased heteroaggregates formation. Based on the study, it was found that the hydrodynamic shear modulated the heterotypic aggregation. At higher shear rates, the intercellular interaction levels were vividly immense. Thrombin treatment didn’t have a profound effect on heterotypic aggregation for higher shear exposure times. The molecular mechanisms of the bacteria-platelets interaction still lie unfolded.

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