Pneumococcal pili and other cell surface properties affect the infection biology of Streptococcus pneumoniae
Year: 2007
Type: dissertation
Abstract: The pneumococcus, Streptococcus pneumoniae, is a major respiratory tract\ndisease causing pathogen with an estimated mortality of 1-2 million per\nyear worldwide. It is the most common bacterial cause of sinusitis,\notitis media and community acquired pneumonia and also a major cause of\ninvasive diseases such as septicaemia and meningitis. Rarely bacteraemia\nis associated with cardiac complications, such as endocarditis and\npericarditis. Pneumococci are also frequent colonizers of the nasopharynx\nof healthy children attending day-care centers and may be considered as\nmucosal commensals of the nasopharyngeal microflora. The aim of this\nthesis was to investigate pneumococcal adhesion factors and other cell\nwall properties involved in the interaction with the human host in regard\nto colonization, virulence, and treatment.\n\nClinical isolates, from patients hospitalised with a pneumococcal\nbacteraemia associated with a pneumococcal endocarditis or pericarditis,\nwere collected and analysed. An associated condition such as pneumonia,\nsinusitis, meningitis or sepsis, appeared to be a prerequisite for\ndisease, and was present in all cases. In the study we found that\nstreptococci seem to require pre-existing endothelial lesions in order to\nadhere to cardiac valves and cause endocarditis. We could not find any\nspecific virulence attributes, such as capsular types or adhesive\nproperties in the examined isolates.\n\nA novel pilus-like structure was found on the surface of pneumococci,\nencoded by the rlrA pathogenicity islet. The rlrA islet contains the\ngenes rlrA, encoding the positive regulator, rrgA, rrgB, rrgC, encoding\nthree structural pili subunits and srtB, srtC, srtD, encoding three\nsortases involved in the linkage and assembly of the pilus structure. We\nfound that the pilus shaft consists of a polymer of RrgB subunits with\nRrgC as the tip protein. RrgA is distributed in intervals along the shaft\nand monomers are also associated with the pneumococcal cell wall. The\npilus is one of the major, but not the only, adherence factor to lung\nepithelial cells. We show that RrgA is the major adhesion among the pilus\nproteins. However, the pilus as such does no seem to be essential for in\nvitro adherence as long as RrgA is present. Our observations also show,\nthat RrgA is the major protein involved in virulence and pathogenicity,\ninducing earlier death and high levels of TNF and IL-6 in murine\ninfection models.\n\nLysis is a characteristic feature of pneumococci. We examined\ncontributions of cell wall charge and pH alterations on LytA-dependent\nstationary phase and antibiotic induced lysis. An exogenous pH below 6 or\nfermentation of glucose and subsequent low pH levels in the growth medium\neffectively abolished lysis but not growth or death of the bacteria.\nPneumococcal cell wall pH levels were detected by FITC emission. We could\nnot find any significant pH changes in the cell wall of bacteria in\nliquid cultures. However, a biofilm model in which non-encapsulated T4R\nand T4RdeltalytA attached as monolayers, showed that treatment with\npenicillin G, vancomycin or valinomycin (a proton motive force\ndissipator), but not the non-lytic erythromycin, led to an instant pH\nshift. This pH shift was dependent upon endogenous H 20 2 production as\nit required an intact pyruvate oxidase gene, spxB, and could be prevented\nwith exogenous addition of catalase.
Source: Figshare
Author: J. Ries
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1893713921