Mucinases and sialidases: their role in the pathogenesis of sexually transmitted infections in the female genital tract

Wiggins, Rebecca; Hicks, Sally J.; Soothill, Peter; Millar, Michael; Corfield, Anthony P.

doi:10.1136/sti.77.6.402

Cited by 131 publications

(122 citation statements)

References 65 publications

(47 reference statements)

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“…Vaginal flora was characterized by Gram stain as normal flora, intermediate flora, or BV, according to published criteria. 16 Samples of vaginal fluid to measure biochemical parameters were collected with three saturated swabs, inoculated into 0.9 mL of sterile phosphate-buffered saline solution (sodium chloride 0.9%), and immediately frozen to -70°C. Sialidase activity was determined by incubation of 50 µL of the vaginal sample with 50 µL of the specific substrate at pH 5.0, as previously described.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, pregnant women with BV or intermediate flora appear to have lower anti-Gvh 15 In addition, desialylation can alter the mucin plug both by altering the charge potential of glycoproteins and by favoring further degradation by proteases. 16 Persistent sialidase activity after antibiotic treatment in pregnant women was associated with an increased risk of preterm birth in one cohort. 17 However, another study did not demonstrate an association between midtrimester cervical sialidase concentrations and preterm birth.…”

Section: Commentmentioning

confidence: 99%

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Vaginal hydrolytic enzymes, immunoglobulin A against Gardnerella vaginalis toxin, and risk of early preterm birth among women in preterm labor with bacterial vaginosis or intermediate flora

Cauci¹,

Hitti²,

Noonan³

et al. 2002

American Journal of Obstetrics and Gynecology

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Bacterial vaginosis (BV) is characterized by a shift in vaginal flora, with a decrease in the prevalence of Lactobacillus and an increase in the prevalence and concentration of anaerobic bacteria, Gardnerella vaginalis, and Mycoplasma hominis. BV, which is consistently associated with preterm delivery, 1,2 is also associated with first-and second-trimester miscarriage, 3,4 amniotic fluid infection, 5,6 histologic chorioamnionitis, 7 and postpartum endometritis. 8 The consistent associations between BV and these markers of upper genital tract infection provide strong indirect evidence that abnormal vaginal flora can ascend to cause bacterial upper genital tract infection and preterm birth. However, most pregnant women with BV have normal pregnancy outcomes.The presence and concentrations of microbial hydrolytic enzymes in women with BV vary. Sialidases (or neuraminidases) are glycosylases that are produced in vitro by several BV-associated bacteria. 9 Prolidase (or proline aminopeptidase) is another hydrolytic enzyme produced by BV-associated bacteria, including G vaginalis and Mobiluncus spp. 10 The only characterized immunogenic virulence factor found in BV thus far is the G vaginalis hemolytic toxin (Gvh). 11,12 The production and concentration of immunoglobulin A (IgA) in response to Gvh in women with BV also vary. Low levels of anti-Gvh IgA in women with BV who are not pregnant are correlated with high levels of vaginal sialidase activity 13 and with cleavage of IgA in vaginal fluid. 14 It remains to be established whether different profiles of these biochemical markers correspond to different levels of risk for poor pregnancy outcome. In the present study, we examined the hypothesis that an increased concentration of sialidase and prolidase and a decreased con- Udine, Italy, Seattle, Wash, and Pittsburgh, Pa OBJECTIVE: The purpose of this study was to determine whether the microbial hydrolytic enzymes, sialidase and prolidase, and immunoglobulin A against the Gardnerella vaginalis cytolysin (anti-Gvh IgA) increase the risk for early preterm birth (≤34 weeks of gestation) among women with bacterial vaginosis or intermediate flora. STUDY DESIGN:Two hundred eighteen afebrile women in preterm labor with intact membranes had a vaginal Gram stain performed, and sialidase, prolidase, and anti-Gvh IgA concentrations were determined. RESULTS: Women with bacterial vaginosis or intermediate flora had significantly higher sialidase and prolidase concentrations than women with normal flora. Among women with bacterial vaginosis or intermediate flora, the women with sialidase had a higher rate of early preterm birth (P = .05). Sialidase had a sensitivity of 43% and specificity of 77% for early preterm birth. Prolidase and anti-Gvh IgA did not predict early preterm birth. CONCLUSION: Women in preterm labor with bacterial vaginosis or intermediate flora and detectable sialidase are at increased risk of early preterm birth. (Am J Obstet Gynecol 2002;187:877-81.)

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Section: Methodsmentioning

confidence: 99%

Section: Commentmentioning

confidence: 99%

Vaginal hydrolytic enzymes, immunoglobulin A against Gardnerella vaginalis toxin, and risk of early preterm birth among women in preterm labor with bacterial vaginosis or intermediate flora

Cauci¹,

Hitti²,

Noonan³

et al. 2002

American Journal of Obstetrics and Gynecology

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“…The sugar moiety consists of galactose, N-acetyl-galactosamine, and either zero, one, or two molecules of sialic acid, resulting in three major proteoforms, apoC-III 0 , apoC-III 1 , and apoC-III 2 , respectively (22,23). Sialylation of apoC-III is catalyzed by sialyltransferases, whereas desialylation of apoC-III is mediated by lysosomal neuraminidase (24). apoC-III proteoforms show substantial functional differences in regulating cellular VLDL uptake in vitro (25).…”

Section: +mentioning

confidence: 99%

Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes

Koška

Yassine

Trenchevska

et al. 2016

Journal of Lipid Research

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“…These bacteria overcome the limited availability of nutrients in the gut (3) by using alternative carbon sources (4). The mammalian intestinal tract is protected by a mucus layer, which contains heavily glycosylated mucin proteins that comprise up to 85% carbohydrate (5,6). Sialic acids, which can be used as an energy source by a variety of microbial pathogens and commensals, are found at the distal ends of the mucin carbohydrate chains (7,8).…”

mentioning

confidence: 99%

Structural insights into the regulation of sialic acid catabolism by the Vibrio vulnificus transcriptional repressor NanR

Hwang

Kim

Jang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Pathogenic and commensal bacteria that experience limited nutrient availability in their host have evolved sophisticated systems to catabolize the mucin sugar N-acetylneuraminic acid, thereby facilitating their survival and colonization. The correct function of the associated catabolic machinery is particularly crucial for the pathogenesis of enteropathogenic bacteria during infection, although the molecular mechanisms involved with the regulation of the catabolic machinery are unknown. This study reports the complex structure of NanR, a repressor of the N-acetylneuraminate (nan) genes responsible for N-acetylneuraminic acid catabolism, and its regulatory ligand, N-acetylmannosamine 6-phosphate (ManNAc-6P), in the human pathogenic bacterium Vibrio vulnificus. Structural studies combined with electron microscopic, biochemical, and in vivo analysis demonstrated that NanR forms a dimer in which the two monomers create an arched tunnel-like DNA-binding space, which contains positively charged residues that interact with the nan promoter. The interaction between the NanR dimer and DNA is alleviated by the ManNAc-6P-mediated relocation of residues in the ligand-binding domain of NanR, which subsequently relieves the repressive effect of NanR and induces the transcription of the nan genes. Survival studies in which mice were challenged with a ManNAc-6P-binding-defective mutant strain of V. vulnificus demonstrated that this relocation of NanR residues is critical for V. vulnificus pathogenesis. In summary, this study presents a model of the mechanism that regulates sialic acid catabolism via NanR in V. vulnificus.nan gene repressor | mucin sugar utilization P athogenic bacteria that colonize the host gut are exposed to an adverse environment and competitors (1, 2). These bacteria overcome the limited availability of nutrients in the gut (3) by using alternative carbon sources (4). The mammalian intestinal tract is protected by a mucus layer, which contains heavily glycosylated mucin proteins that comprise up to 85% carbohydrate (5, 6). Sialic acids, which can be used as an energy source by a variety of microbial pathogens and commensals, are found at the distal ends of the mucin carbohydrate chains (7,8). Because the most abundant sialic acid is N-acetylneuraminic acid (Neu5Ac) (7-9), intestinal commensal and pathogenic bacteria have most likely evolved elaborate systems for the catabolic utilization of this substrate.Escherichia coli, Vibrio cholerae, Vibrio vulnificus, and Staphylococcus aureus can grow by using Neu5Ac as a sole carbon source (10-13), and the N-acetylneuraminate (nan) genes responsible for Neu5Ac utilization are up-regulated during their growth on mucus or in the mammalian intestine (3,14). The colonization and pathogenic activities of these bacteria are affected severely by mutations in the nan genes (3, 12, 15). This phenotype suggests that the correct expression and function of the proteins responsible for Neu5Ac catabolism are essential for the growth and survival of enteric bacteria, although onl...

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Mucinases and sialidases: their role in the pathogenesis of sexually transmitted infections in the female genital tract

Cited by 131 publications

References 65 publications

Vaginal hydrolytic enzymes, immunoglobulin A against Gardnerella vaginalis toxin, and risk of early preterm birth among women in preterm labor with bacterial vaginosis or intermediate flora

Vaginal hydrolytic enzymes, immunoglobulin A against Gardnerella vaginalis toxin, and risk of early preterm birth among women in preterm labor with bacterial vaginosis or intermediate flora

Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes

Structural insights into the regulation of sialic acid catabolism by the Vibrio vulnificus transcriptional repressor NanR

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