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Modulation of effector function of macrophages by ESBL producer Klebsiella pneumoniae

Grant number: 14/26947-7
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): March 01, 2015
Effective date (End): December 31, 2015
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Alexandra Ivo de Medeiros
Grantee:Flávio de Campos Mello Monteiro
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Klebsiella pneumoniae, a member of Enterobacteriacea family, is a Gram negative bacillus responsible for the major percentage of community acquired bacterial pneumonia. Besides, it is the main causative agent of nosocomial infections by the gender Klebsiella and therefore the most important clinical species. Main virulence factors of K. pneumoniae are: synthesis of capsular polysaccharide (CPS), production of lipopolysaccharide (LPS) and siderophores and adhesins. Although K. pneumoniae infections may occur in any site, urinary and respiratory tracts are stricken more often than others, in a way that K. pneumoniae is related to 10 - 13% of pulmonary infections cases. Neutrophils and macrophages have a crucial role in clearance of pathogens due to their high phagocytic and microbicidal capacities, involving the production of inflammatory mediators such as IL-1², TNF-± and KC , important to enhance cell recruitment and the activity of these cells, improving the production of reactive oxygen and nitrogen species as nitric oxide and hydrogen peroxide, important microbicidal factors. Nevertheless, K. pneumoniae stands by many scape mechanisms to evade immune system, such as CPS and molecular changes in LPS. In addition, K. pneumoniae is getting multiple resistances to different drugs. This study aims to understand possible scape mechanisms from effector functions of macrophages by ESBL-producing K. pneumoniae strains obtained from clinical isolates. The hypothesis of our study is that different ESBL-producing strains could negatively modulate macrophage effector functions, as phagocytosis and microbicidal activity, leading to proliferation and dissemination of the bacteria, leading to the host death.