Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phenotypic serum resistance of gonococci in urethral exudates is due to sialylation of lipopolysaccharide (LPS) by host cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA). A surface structure was visible on gonococci [strain BS4 (agar)] that had been stained with ruthenium red after incubation with CMP-NANA. This structure was not visible after neuraminidase treatment, which released sialic acid but not LPS. The LPS profiles of strain BS4 (agar) had another in vivo-selected strain Gc40 (variant D1), were similar. A monoclonal antibody (mAb) which recognises epitope C on the LPS of 'capsulated' gonococci was shown by immunoblotting to react with several LPS components, including one of about 4.5 kDa which contains the probable site of sialylation by CMP-NANA. The reactions with the mAb were not affected by growing the strains with CMP-NANA nor by neuraminidase treatment of the sialylated LPS. The mAb also gold-labelled the surface of both strains before and after treatment with CMP-NANA. These data indicate that sialylation by CMP-NANA and staining with ruthenium red renders more visible the surface LPS which, sometimes in the past, has been seen as a 'capsule'.
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PMID:The surface structure seen on gonococci after treatment with CMP-NANA is due to sialylation of surface lipopolysaccharide previously described as a 'capsule'. 172 90

The determinant(s) of gonococcal resistance to killing by human phagocytes has been extracted from outer membrane vesicles (OMV) of a phagocyte-resistant strain, BS4 (agar), with sodium cholate (1%, w/v). The extracts, like the OMV, nullified the effect of antiserum raised against whole BS4 (agar) to promote intracellular killing of the latter by human peripheral blood phagocytes. Fractionation of the extract on Sephadex G75 produced an active fraction with much less protein and lipopolysaccharide (LPS) than in the original extract. Furthermore, crude LPS prepared from the resistant gonococci was inactive. These results imply that the factor(s) promoting intracellular resistance is a protein. SDS-PAGE of the active fraction suggested that the factor was not a principal outer membrane protein nor one of three proteins previously thought to be associated with resistance. In contrast to a similar preparation from a phagocyte-susceptible strain, BSSH, the active fraction from BS4 (agar) showed faintly staining proteins in the regions of 20 and 60 kDal. When eluted from the gels, the former but not the latter neutralized the above effect of antisera, thus associating the 20 kDal protein(s) with resistance to intracellular killing.
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PMID:Association of resistance of Neisseria gonorrhoeae to killing by human phagocytes with outer-membrane proteins of about 20 kilodaltons. 241 May 44

A protein of about 20 kDa was extracted by sodium cholate (1%, w/v) from outer membranes of a strain of Neisseria gonorrhoeae, BS4 (agar), which is resistant to killing by human phagocytes. When the protein was purified by repeated fractionation on Sephadex G75, contamination with other outer-membrane proteins and lipopolysaccharide was negligible. The protein contained a full complement of amino acids, with high levels of glutamic acid. Carbohydrate, detected by the anthrone method and by sugar and hexosamine analysis, was present, but at very low levels. There was a significant content of fatty acids (about 5.7% of the protein), indicating a lipoprotein. The 20 kDa lipoprotein: (1) neutralized the ability of antiserum against whole organisms of BS4 (agar) to reduce the resistance of this strain to phagocyte killing; (2) evoked in mice an antiserum which reduced this resistance and immunoblotted only with 20 kDa lipoprotein in the cholate extract of outer membranes; and (3) promoted resistance to intracellular killing of an otherwise phagocyte susceptible gonococcal strain (BSSH). This is strong evidence that it is a determinant of gonococcal resistance to phagocyte killing.
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PMID:A determinant of resistance of Neisseria gonorrhoeae to killing by human phagocytes: an outer membrane lipoprotein of about 20 kDa with a high content of glutamic acid. 288 33

On SDS-PAGE, solubilized and proteinase K treated preparations of Neisseria gonorrhoeae strain BS4 (agar) showed differences in silver stained lipopolysaccharide (LPS) patterns, before and after induction to resistance to serum killing by incubation for 3 h at 37 degrees C with low Mr fractions from lysates of guinea pig red blood cells. Preparations from the original serum susceptible gonococci and LPS purified from such bacteria showed two components, but the preparations from the serum resistant gonococci were deficient in the higher Mr component. Furthermore, on immunoblotting with fresh human serum (FHS), the two LPS components of the susceptible gonococci reacted strongly with IgM. With preparations from the serum resistant gonococci there was no reaction in the area corresponding to the higher Mr component and a weaker reaction with the component of low Mr. Purified LPS from the susceptible gonococci neutralized the bactericidal activity of FHS against N. gonorrhoeae strain BS4 (agar) probably by reacting with the relevant antibody, since heated FHS was no longer bactericidal when mixed with a source of complement (human placental serum) after prior reaction with the LPS. These neutralization tests coupled with the results of immunoblotting strongly suggest that increased serum resistance is due to the lack of the high Mr LPS moiety.
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PMID:Lipopolysaccharide alteration is associated with induced resistance of Neisseria gonorrhoeae to killing by human serum. 309 92

Recently evidence has been obtained that a minute amount of cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA) or a closely related compound is the low Mr factor in human red blood cells which induces Neisseria gonorrhoeae (BS4(agar] to resistance to killing by fresh human serum. Induction of gonococci to resistance by both CMP-NANA and semi-purified low Mr factor from red blood cells was accompanied by a 35-55% reduction of silver staining of lipopolysaccharide separated in SDS-PAGE gels of proteinase K digests. These alterations in lipopolysaccharide are probably responsible for conferring serum resistance. However, lipopolysaccharide-containing digests from resistant as well as from susceptible gonococci neutralised serum bactericidal activity. These observations may have wider implications since CMP-NANA is a sialylating agent wide-spread in mammalian tissues and LPS is ubiquitous amongst Gram-negative pathogens.
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PMID:Cytidine 5'-monophospho-N-acetyl neuraminic acid and a low molecular weight factor from human blood cells induce lipopolysaccharide alteration in gonococci when conferring resistance to killing by human serum. 314 16

Gonococci (strain BS4(agar)), emerging from lag-phase during 1-1.5 h incubation in a medium containing glucose (28 mM) and either 5 microM or 50 microM sodium lactate, show enhanced capacity for their lipopolysaccharide (LPS) to be sialylated by cytidine 5'-monophospho-N-acetyl neuraminic acid. The sialyltransferase content of the lactate-treated gonococci was not greater than that of control organisms and showed no differences in LPS components. However, the total LPS content of the lactate-treated gonococci was 10-20% higher than that of control organisms, so lactate enhancement may be due to more sialyl receptors becoming available due to an overall stimulation of LPS synthesis. The protein and pentose contents of the lactate-treated gonococci were also higher than those of controls, indicating stimulation of protein synthesis and ribosome production. Electron microscopy showed hair-like external appendages on control but not on lactate-treated gonococci. The above growth conditions are unnatural. However, when concentrations of glucose and lactate were adjusted to values akin to those occurring in vivo (glucose 5 mM alone and with either 1 mM or 10 mM lactate), and gonococcal multiplication occurred during the short incubation period (1-1.5 h), lactate again induced greater contents of LPS, protein and pentose. A high content of LPS, which will contribute to pathogenicity, should be a constant feature of gonococci growing in human urogenital tissues, where lactate is ever present with glucose.
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PMID:Lactate causes changes in gonococci including increased lipopolysaccharide synthesis during short-term incubation in media containing glucose. 986 75

Promotion of uptake of essential metabolites is a possible reason for the general stimulation of gonococcal metabolism which is caused by lactate (1 mM) in a defined medium containing glucose (5 mM). However, although uptake of(14)C adenine by gonococci [strain BS4(agar)] held for 4 or 7 min at 37 degrees C in Hanks balanced salt solution was increased for lactate treated gonococci compared with control organisms, uptake of(14)C glucose and(14)C proline under these conditions was unaffected. Hence, there is no evidence that lactate produces general stimulation of metabolite uptake. Unlike the other metabolites, cytidine 5'-monophospho-(14)CN-acetyl neuraminic acid (CMP-(14)CNANA), the substrate for sialylation of gonococcal lipopolysaccharide (LPS), was adsorbed in substantial quantities by gonococci held on ice for 6 min. Also, the increase in uptake of CMP-(14)CNANA at 37 degrees C over that adsorbed at 0 degrees C was much smaller (less than two-fold) than for the other compounds (4-30-fold). The substantial adsorption at 0 degrees C suggested a surface receptor for CMP-(14)CNANA. It is probably the sialyltransferase because a sialyltransferase deficient mutant, JB1, did not absorb CMP-(14)CNANA at 0 degrees C or take it up at 37 degrees C, in contrast to its parent strain, F62, which behaved similarly to strain BS4 (agar). This supports previous evidence for a surface location of the sialyltransferase. There was a small increase in adsorption of CMP-(14)CNANA in lactate treated gonococci indicating a slight increase in the surface enzyme. This could enhance LPS sialylation and hence affect pathogenicity.
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PMID:Uptake of metabolites by gonococci grown with lactate in a medium containing glucose: evidence for a surface location of the sialyltransferase. 1079 76