scholarly journals Mast cell degranulation by a hemolytic lipid toxin decreases GBS colonization and infection

2015 ◽  
Vol 1 (6) ◽  
pp. e1400225 ◽  
Author(s):  
Claire Gendrin ◽  
Jay Vornhagen ◽  
Lisa Ngo ◽  
Christopher Whidbey ◽  
Erica Boldenow ◽  
...  
Keyword(s):  
Mast Cell ◽  
Preterm Birth ◽  
Genital Tract ◽  
Mast Cell Degranulation ◽  
Microbial Infection ◽  
Amniotic Cavity ◽  
Proinflammatory Mediators ◽  
Ascending Infection ◽  
Lower Genital Tract ◽  
Deficient Mice

Ascending infection of microbes from the lower genital tract into the amniotic cavity increases the risk of preterm birth, stillbirth, and newborn infections. Host defenses that are critical for preventing ascending microbial infection are not completely understood. Group BStreptococcus(GBS) are Gram-positive bacteria that frequently colonize the lower genital tract of healthy women but cause severe infections during pregnancy, leading to preterm birth, stillbirth, or early-onset newborn infections. We recently described that the GBS pigment is hemolytic, and increased pigment expression promotes GBS penetration of human placenta. Here, we show that the GBS hemolytic pigment/lipid toxin and hyperpigmented GBS strains induce mast cell degranulation, leading to the release of preformed and proinflammatory mediators. Mast cell–deficient mice exhibit enhanced bacterial burden, decreased neutrophil mobilization, and decreased immune responses during systemic GBS infection. In a vaginal colonization model, hyperpigmented GBS strains showed increased persistence in mast cell–deficient mice compared to mast cell–proficient mice. Consistent with these observations, fewer rectovaginal GBS isolates from women in their third trimester of pregnancy were hyperpigmented/hyperhemolytic. Our work represents the first example of a bacterial hemolytic lipid that induces mast cell degranulation and emphasizes the role of mast cells in limiting genital colonization by hyperpigmented GBS.

scholarly journals A hemolytic pigment of Group B Streptococcus allows bacterial penetration of human placenta

2013 ◽  
Vol 210 (6) ◽  
pp. 1265-1281 ◽  
Author(s):  
Christopher Whidbey ◽  
Maria Isabel Harrell ◽  
Kellie Burnside ◽  
Lisa Ngo ◽  
Alexis K. Becraft ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Amniotic Fluid ◽  
Preterm Labor ◽  
Group B Streptococcus ◽  
Dependent Manner ◽  
Microbial Infection ◽  
Amniotic Cavity ◽  
Protein Toxin ◽  
Ascending Infection ◽  
Group B

Microbial infection of the amniotic fluid is a significant cause of fetal injury, preterm birth, and newborn infections. Group B Streptococcus (GBS) is an important human bacterial pathogen associated with preterm birth, fetal injury, and neonatal mortality. Although GBS has been isolated from amniotic fluid of women in preterm labor, mechanisms of in utero infection remain unknown. Previous studies indicated that GBS are unable to invade human amniotic epithelial cells (hAECs), which represent the last barrier to the amniotic cavity and fetus. We show that GBS invades hAECs and strains lacking the hemolysin repressor CovR/S accelerate amniotic barrier failure and penetrate chorioamniotic membranes in a hemolysin-dependent manner. Clinical GBS isolates obtained from women in preterm labor are hyperhemolytic and some are associated with covR/S mutations. We demonstrate for the first time that hemolytic and cytolytic activity of GBS is due to the ornithine rhamnolipid pigment and not due to a pore-forming protein toxin. Our studies emphasize the importance of the hemolytic GBS pigment in ascending infection and fetal injury.

scholarly journals OP02.10: Lower genital tract infection by HPV: correlation with HPV-induced trophoblastic dysfunction in late preterm birth

2014 ◽  
Vol 44 (S1) ◽  
pp. 67-67
Author(s):  
P. Breton Hernandez ◽  
M. Garcés Valenzuela ◽  
E. Moreno Romea ◽  
C. Paules Tejero ◽  
R. Benito ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Tract Infection ◽  
Genital Tract ◽  
Late Preterm ◽  
Genital Tract Infection ◽  
Late Preterm Birth ◽  
Lower Genital Tract ◽  
Lower Genital Tract Infection

scholarly journals Hyaluronidase Impairs Neutrophil Function and Promotes Group B Streptococcus Invasion and Preterm Labor in Nonhuman Primates

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Michelle Coleman ◽  
Blair Armistead ◽  
Austyn Orvis ◽  
Phoenicia Quach ◽  
Alyssa Brokaw ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Preterm Labor ◽  
Bacterial Invasion ◽  
Group B Streptococci ◽  
Primate Model ◽  
Amniotic Cavity ◽  
Human Pregnancy ◽  
Lower Genital Tract ◽  
Group B ◽  
Maternal Fetal Interface

ABSTRACT Invasive bacterial infections during pregnancy are a major risk factor for preterm birth, stillbirth, and fetal injury. Group B streptococci (GBS) are Gram-positive bacteria that asymptomatically colonize the lower genital tract but infect the amniotic fluid and induce preterm birth or stillbirth. Experimental models that closely emulate human pregnancy are pivotal for the development of successful strategies to prevent these adverse pregnancy outcomes. Using a unique nonhuman primate model that mimics human pregnancy and informs temporal events surrounding amniotic cavity invasion and preterm labor, we show that the animals inoculated with hyaluronidase (HylB)-expressing GBS consistently exhibited microbial invasion into the amniotic cavity, fetal bacteremia, and preterm labor. Although delayed cytokine responses were observed at the maternal-fetal interface, increased prostaglandin and matrix metalloproteinase levels in these animals likely mediated preterm labor. HylB-proficient GBS dampened reactive oxygen species production and exhibited increased resistance to neutrophils compared to an isogenic mutant. Together, these findings demonstrate how a bacterial enzyme promotes GBS amniotic cavity invasion and preterm labor in a model that closely resembles human pregnancy. IMPORTANCE Group B streptococci (GBS) are bacteria that commonly reside in the female lower genital tract as asymptomatic members of the microbiota. However, during pregnancy, GBS can infect tissues at the maternal-fetal interface, leading to preterm birth, stillbirth, or fetal injury. Understanding how GBS evade host defenses during pregnancy is key to developing improved preventive therapies for these adverse outcomes. In this study, we used a unique nonhuman primate model to show that an enzyme secreted by GBS, hyaluronidase (HylB) promotes bacterial invasion into the amniotic cavity and fetus. Although delayed immune responses were seen at the maternal-fetal interface, animals infected with hyaluronidase-expressing GBS exhibited premature cervical ripening and preterm labor. These observations reveal that HylB is a crucial GBS virulence factor that promotes bacterial invasion and preterm labor in a pregnancy model that closely emulates human pregnancy. Therefore, hyaluronidase inhibitors may be useful in therapeutic strategies against ascending GBS infection.

scholarly journals Chlamydial Plasmid-Encoded Virulence Factor Pgp3 Neutralizes the Antichlamydial Activity of Human Cathelicidin LL-37

2015 ◽  
Vol 83 (12) ◽  
pp. 4701-4709 ◽  
Author(s):  
Shuping Hou ◽  
Xiaohua Dong ◽  
Zhangsheng Yang ◽  
Zhongyu Li ◽  
Quanzhong Liu ◽  
...  
Keyword(s):  
Genital Tract ◽  
Therapeutic Agents ◽  
Middle Region ◽  
Tubal Infertility ◽  
Significant Information ◽  
Content Type ◽  
Ascending Infection ◽  
Lower Genital Tract ◽  
Novel Therapeutic

Chlamydia trachomatisinfection in the lower genital tract can ascend to and cause pathologies in the upper genital tract, potentially leading to severe complications, such as tubal infertility. However, chlamydial organisms depleted of plasmid or deficient in the plasmid-encoded Pgp3 are attenuated in ascending infection and no longer are able to induce the upper genital tract pathologies, indicating a significant role of Pgp3 in chlamydial pathogenesis. We now report thatC. trachomatisPgp3 can neutralize the antichlamydial activity of human cathelicidin LL-37, a host antimicrobial peptide secreted by both genital tract epithelial cells and infiltrating neutrophils. Pgp3 bound to and formed stable complexes with LL-37. We further showed that the middle region of Pgp3 (Pgp3m) was responsible for both the binding to and neutralization of LL-37, suggesting that Pgp3m can be targeted for attenuating chlamydial pathogenicity or developed for blocking LL-37-involved non-genital-tract pathologies, such as rosacea and psoriasis. Thus, the current study has provided significant information for both understanding the mechanisms of chlamydial pathogenesis and developing novel therapeutic agents.

scholarly journals The Microbiome and Preterm Birth: A Change in Paradigm with Profound Implications for Pathophysiologic Concepts and Novel Therapeutic Strategies

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Birte Staude ◽  
Frank Oehmke ◽  
Tina Lauer ◽  
Judith Behnke ◽  
Wolfgang Göpel ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Neonatal Intensive Care ◽  
Early Stage ◽  
Amniotic Cavity ◽  
Balanced Development ◽  
Global Challenge ◽  
Stage Of Development ◽  
Lower Genital Tract ◽  
Therapeutic Concepts ◽  
Novel Therapeutic Strategies

Preterm birth poses a global challenge with a continuously increasing disease burden during the last decades. Advances in understanding the etiopathogenesis did not lead to a reduction of prematurely born infants so far. A balanced development of the host microbiome in early life is key for the maturation of the immune system and many other physiological functions. With the tremendous progress in new diagnostic possibilities, the contribution of microbiota changes to preterm birth and the acute and long-term sequelae of prematurity have come into the research focus. This review summarizes the latest advances in the understanding of microbiomes in the amniotic cavity and the female lower genital tract and how changes in microbiota structures contribute to preterm delivery. The exhibition of these highly vulnerable infants to the hostile environment in the neonatal intensive care unit necessarily entails the rapid colonization with a nonbalanced microbiome in a situation where the organism is still very prone and at an early stage of development. The global research efforts to decipher pathologic changes will pave the way to new pre- and postnatal therapeutic concepts.

Vulvovaginitis of mixed etiology and real clinical practice

GYNECOLOGY ◽  
2020 ◽  
Vol 22 (4) ◽  
pp. 82-87
Author(s):  
Vera N. Prilepskaya ◽  
Patimat R. Abakarova ◽  
Andrei E. Donnikov
Keyword(s):  
Genital Tract ◽  
Inflammatory Diseases ◽  
Mixed Infections ◽  
Pathogenic Microorganisms ◽  
Ascending Infection ◽  
Lower Genital Tract ◽  
Wide Range ◽  
Frequent Relapses ◽  
The One ◽  
Combined Drugs

Lower genital tract inflammatory diseases, caused by opportunistic and pathogenic microorganisms (vulvovaginitis), occupy a leading place among gynecological diseases and are one of the most common reasons for women to consult an obstetrician-gynecologist. Vulvovaginitis is rarely caused by a single pathogen. In recent years, lower genital tract inflammatory diseases are characterized by the predominance of mixed infections, which, on the one hand, can lead to a more severe and prolonged course, frequent relapses, an ascending infection, and, on the other hand, can be asymptomatic, till the development of complications, and represent certain difficulties in the diagnosis and choice of therapy. Opportunistic pathogens and anaerobes-bacteroides play a major role in manifestations of mixed infections. Currently, in the treatment of mixed vulvovaginitis, preference is given to combined drugs that have an effect on a wide range of pathogenic microorganisms. One of them is Metromicon-Neo, which features of action and our experience of its use along with the features of mixed vulvovaginitis are summarized in the article.

scholarly journals The neuropeptide neuromedin U promotes inflammation by direct activation of mast cells

2005 ◽  
Vol 202 (2) ◽  
pp. 217-224 ◽  
Author(s):  
Maiko Moriyama ◽  
Takahiro Sato ◽  
Hiromasa Inoue ◽  
Satoru Fukuyama ◽  
Hitoshi Teranishi ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Neutrophil Infiltration ◽  
Mast Cell Degranulation ◽  
Plasma Extravasation ◽  
Intraplantar Injection ◽  
Peripheral Tissues ◽  
Deficient Mice

Neuromedin U (NMU) is a neuropeptide that is expressed in the gastrointestinal tract and central nervous system. NMU interacts with two G protein–coupled receptors, NMU-R1 and NMU-R2. Whereas NMU-R2 localizes predominantly to nerve cells, NMU-R1 is expressed in peripheral tissues including lymphocytes and monocytes, suggesting a role of NMU in immunoregulation. However, the functions of NMU in peripheral tissues have not been clarified. In this study, using NMU-deficient mice, we first demonstrated that NMU plays an important role in mast cell-mediated inflammation. Complete Freund's adjuvant-induced mast cell degranulation as well as edema and neutrophil infiltration, which occurred weakly in mast cell–deficient WBB6F1-W/Wv mice, did not occur in NMU-deficient mice. Moreover, intraplantar injection of NMU into paws induced early inflammatory responses such as mast cell degranulation, vasodilation, and plasma extravasation in WT mice but not in WBB6F1-W/Wv mice. NMU-R1 was highly expressed in primary mast cells, and NMU induced Ca2+ mobilization and degranulation in peritoneal mast cells. These data indicate that NMU promotes mast cell–mediated inflammation; therefore, NMU receptor antagonists could be a novel target for pharmacological inhibition of mast cell–mediated inflammatory diseases.

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