Serum Resistance of <i>Neisseria gonorrhoeae</i> Does It Thwart the Inflammatory Response and Facilitate the Transmission of Infection?a

Rice, Peter A.; McQuillen, Daniel P.; Gulati, Sunita; Jani, Darshana; Wetzler, Lee M.; Blake, M. S.; Gotschlich, Emil C.

doi:10.1111/j.1749-6632.1994.tb44234.x

Cited by 23 publications

(14 citation statements)

References 18 publications

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“…In contrast, antibodies against Rmp, which is conserved, were associated with enhanced likelihood of gonococcal infection in commercial sex workers in Kenya [27]. It is noteworthy that anti-Rmp antibodies block killing of gonococci by bactericidal antibodies [38].…”

Section: Discussionmentioning

confidence: 96%

Immunization against a Saccharide Epitope Accelerates Clearance of Experimental Gonococcal Infection

et al. 2013

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The emergence of ceftriaxone-resistant strains of Neisseria gonorrhoeae may herald an era of untreatable gonorrhea. Vaccines against this infection are urgently needed. The 2C7 epitope is a conserved oligosaccharide (OS) structure, a part of lipooligosaccharide (LOS) on N gonorrhoeae. The epitope is expressed by 94% of gonococci that reside in the human genital tract (in vivo) and by 95% of first passaged isolates. Absence of the 2C7 epitope shortens the time of gonococcal carriage in a mouse model of genital infection. To circumvent the limitations of saccharide immunogens in producing long lived immune responses, previously we developed a peptide mimic (called PEP1) as an immunologic surrogate of the 2C7-OS epitope and reconfigured it into a multi-antigenic peptide, (MAP1). To test vaccine efficacy of MAP1, female BALB/c mice were passively immunized with a complement-dependent bactericidal monoclonal antibody specific for the 2C7 epitope or were actively immunized with MAP1. Mice immunized with MAP1 developed a TH1-biased anti-LOS IgG antibody response that was also bactericidal. Length of carriage was shortened in immune mice; clearance occurred in 4 days in mice passively administered 2C7 antibody vs. 6 days in mice administered control IgG3λ mAb in one experiment (p = 0.03) and 6 vs. 9 days in a replicate experiment (p = 0.008). Mice vaccinated with MAP1 cleared infection in 5 days vs. 9 days in mice immunized with control peptide (p = 0.0001 and p = 0.0002, respectively in two replicate experiments). Bacterial burden was lower over the course of infection in passively immunized vs. control mice in both experiments (p = 0.008 and p = 0.0005); burdens were also lower in MAP1 immunized mice vs. controls (p<0.0001) and were inversely related to vaccine antibodies induced in the vagina (p = 0.043). The OS epitope defined by mAb 2C7 may represent an effective vaccine target against gonorrhea, which is rapidly becoming incurable with currently available antibiotics.

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Section: Discussionmentioning

confidence: 96%

Immunization against a Saccharide Epitope Accelerates Clearance of Experimental Gonococcal Infection

et al. 2013

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“…Others have shown differences between immune responses and vaccine efficacy among different mouse strains (46). In other Gram-negative bacteria, development of blocking antibodies against OMPs and of serum resistance has been demonstrated (47). Blocking antibodies directed against an N. meningitidis lipoprotein reduced meningococcal killing (48).…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis and Immunogenicity of Mannheimia haemolytica Vesicles

Ayalew

Confer

Shrestha

et al. 2013

Clin Vaccine Immunol

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b Mannheimia haemolytica, a major causative agent in bovine respiratory disease, inflicts extensive losses each year on cattle producers. Commercially available vaccines are only partially efficacious. Immunity to M. haemolytica requires antibodies to secreted toxins and outer membrane proteins (OMPs) of the bacterium. Gram-negative bacteria produce membrane blebs or vesicles, the membrane components of which are primarily derived from OMPs. Accordingly, vesicles have been used as immunogens with various degrees of success. This study characterized components of M. haemolytica vesicles and determined their immunogenicity in mice and cattle. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of vesicles from this bacterium identified 226 proteins, of which 58 (25.6%) were OMPs and periplasmic and one (0.44%) was extracellular. Vesicles were used to vaccinate dairy calves and BALB/c mice. Analyses of sera from calves and mice by enzyme-linked immunosorbent assay (ELISA) showed that circulating antibodies against M. haemolytica whole cells and leukotoxin were significantly higher on days 21 and 28 (P < 0.05) than on day 0. For control calves and mice, there were no significant differences in serum anti-whole-cell and leukotoxin antibody levels from days 0 and 21 or 28, respectively. Lesion scores of lungs from vaccinated calves (15.95%) were significantly (P < 0.05) lower than those from nonvaccinated calves (42.65%). Sera from mice on day 28 and calves on day 21 showed 100% serum bactericidal activity. Sera from vesicle-vaccinated mice neutralized leukotoxin.

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“…This phenomenon may be due to extracellular inactivation of the complement by the lipopolysaccharide components of the N. gonorrhoeae cell wall which accumulate in the medium during culturing. This mechanism of escaping the bactericidal effect of the complement is probable in vivo, where it may lead to a local decrease in the activity of the complement system in a focus of intlammation [12].…”

Section: Resultsmentioning

confidence: 99%

Differences in antiopsonic effects of the extracellular products ofS. aureus andN. gonorrhoeae

et al. 1998

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Extracellular products of S. aureus and N. gonorrhoeae decrease the etficacy of opsonization of these bacteria by blood serum. Antiopsonic activity of S. aureus exometabolites is exhibited predominantly during their contact with serum components bound to bacterial surface, which disturbed the reactions between opsonines and neutrophiis, as evidenced by decreased chemiluminescent signal during phagocytosis. With gonococci, this effect was observed predominantly during preliminary contact of their extracellular products with the serum, which attenuated the intensity of opsonization. Partial parallelism between changes in the neutrophil-stimulating activity of bacterial cultures and modification of their hydrophobic properties under the effect of the studied factors cannot be regarded as an absolute relationship. Key Words: Staphylococcus aureus; Neisseria gonorrhoeae; complement; opsonization; hydrophobic properties; chemiluminescenceThe reactions between microorganisms and neutrophilic phagocytes are a key component in the pathogenesis of staphylococcal and neisserial infections. Along with the resistance to the intracellular killing, the avoidance of the phagocytic reaction of a host organism is an important factor [8,13]. We have demonstrated this reaction in Staphylococcus aureus [3]: the efficacy of opsonization of bacterial cells by serum components was reduced by the extracellular protein A that shielded the Fc fragments of bound immunoglobulins and by an anticomplementary factor. The ability of Neisseria gonorrhoeae to inactivate the complement (mainly its C1 and C3 components) by the extracellular products [1] prompted us to investigate the probable antiopsonic effect and analyze the simiInstitute of Cellular and Extracellular Symbiosis, Ural Branch of the Russian Academy of Sciences, Orenbur~ larities and differences in the mechanisms of antiopsonic effects of staphylococcal and gonococcal products.We also studied modifications in the hydrophopic properties of staphylococci and gonococci caused by fixation of serum components. The need in this comparison is explained by important role of physical properties of bacterial surface for adhesion to eukaryotic cells, including the opsonization [14] and other processes associated with specific adhesion mechanisms [9]. It should be noted that the relationship between the hydrophobic properties of bacterial surface and its phagocyte-stimulating ability is poorly understood. MATERIALS AND METHODSTwelve S. aureus strains isolated from patients with pyointlammatory diseases of staphylococcal etiology and identified by biological and biochemical (Staphy-

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Serum Resistance of Neisseria gonorrhoeae Does It Thwart the Inflammatory Response and Facilitate the Transmission of Infection?a

Cited by 23 publications

References 18 publications

Immunization against a Saccharide Epitope Accelerates Clearance of Experimental Gonococcal Infection

Immunization against a Saccharide Epitope Accelerates Clearance of Experimental Gonococcal Infection

Proteomic Analysis and Immunogenicity of Mannheimia haemolytica Vesicles

Differences in antiopsonic effects of the extracellular products ofS. aureus andN. gonorrhoeae

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