Oligosaccharides Interfere with the Establishment and Progression of Experimental Pneumococcal Pneumonia

Abstract

Oligosaccharides that block the adherence of bacteria to epithelial cells in vitro--lacto-N-neotetraose (LNnT) and its alpha2-3- and alpha2-6-sialylated derivatives--were tested for their abilities to attenuate the course of pneumococcal pneumonia and to prevent colonization of the nasopharynx in animal models. Intratracheal administration of these agents concurrently with bacteria dramatically decreased pneumococcal load in the lungs of rabbits and conferred protection from bacteremia. The oligosaccharides ameliorated pneumonia and bacteremia when given therapeutically 24 h after infection was established. When administered intranasally, neoglycoconjugates of the active oligosaccharides prevented colonization of the nasopharynx of infant rats. In addition to in vitro anti-adherence properties, LNnT acted directly on cultured lung epithelial cell lines to induce changes such that pneumococcal adherence was prevented for prolonged periods. These activities encourage continued development of oligosaccharides as a class of potentially preventive and therapeutic agents for infectious diseases.

Human Milk Oligosaccharides Inhibit the Adhesion to Caco-2 Cells of Diarrheal Pathogens: Escherichia coli, Vibrio cholerae, and Salmonella fyris

“…As for S. pneumoniae, Anderson et al (18) proved in 1986 that lacto-N-tetraose (LNT) and lacto-Nneotetraose (LNnT) can inhibit the adhesion to buccal epithelial cells. The same positive effect of LNnT was also confirmed on lung tumoral cells and animal models (38). On the contrary, Barthelson et al (39), using conjunctival cells, observed a reduced effectiveness of LNnT in inhibiting some Streptococcus strains, while its 6= sialyl-derivative was very effective.…”

Inhibition of lectin adherence to tissue culture cells by prebiotic carbohydrates

“…For example, P-fimbriated uropathogenic Escherichia coli strains contain an adhesin specific for Galα1-4Gal [19], whereas other E. coli, as well as Klebsiella pneumoniae and Salmonella, produce adhesins that bind to mannose residues [1,[20][21][22][23][24]. In contrast, the gram positive organism, Streptococcus pneumonia, binds carbohydrates containing the linkages Galβ1-3GalNAc and Galβ1-4GluNAc [5,25,26]. The observation that all of these organisms adhere to HEp-2 cells suggests the presence of a diverse array of carbohydrates receptors to which their adhesins are able to bind [20,[26][27][28][29].…”

Nebulised Heparin Is Associated With Fewer Days Of Mechanical Ventilation In Critically Ill Patients: A Randomised Controlled Trial

“…This methodological limitation may also be a factor in the finding of similar levels of inflammatory mediators (IL-6, IL-8, and TNF) and markers of lung damage (SP-D, CC-16, and RAGE) in the pulmonary lavage fluid of the two groups [46]. Previous studies have suggested that heparin may inhibit growth of bacteria and viruses in the lungs through limiting their adhesion to respiratory surfaces [20][21][22]. We did not find evidence to support this, and there were similar numbers of new positive bacterial cultures in pulmonary lavage fluid in both groups following enrollment.…”

“…Clinical and experimental models have demonstrated that heparin or other anti-coagulants reduce fibrin deposition in the lungs and improve clinical outcomes [13][14][15][16][17]. Heparin has other actions, including reduced pulmonary edema, reduced leukocyte activation, and inhibition of adhesion of bacteria and viruses to respiratory surfaces, that may also be beneficial [18][19][20][21][22]. Evidence from large, multi-center, clinical studies in patients with severe sepsis also suggests that heparin may improve important clinical outcomes.…”