Maternal/fetal mortality and fetal growth restriction: role of nitric oxide and virulence factors in intrauterine infection in rats

Abstract

Objective-The mechanism of infection-related mortality of pregnant rats and the intrauterine growth restriction (IUGR) are not understood. We assessed if nitric oxide (NO) has differential effects on infection with E. coli Dr/Afa mutants lacking either AfaE or AfaD invasins.Material and Methods-Sprague-Dawley rats were intrauterinally infected with the clinical strain of E. coli AfaE + D + or one of its isogenic mutants in the presence or absence of the NO synthesis inhibitor N G -nitro-L-arginine methyl ester (L-NAME). Maternal/fetal mortality, fetoplacental weight, and the infection rate were evaluated.Results-Maternal and/or fetal mortality was associated with the presence of at least one virulence factor (AfaE + D + >AfaE + D − >AfaE-D + ) and was increased by L-NAME treatment. The fetal and placental weights were lower than controls and they were further reduced by L-NAME treatment.Conclusions-These results demonstrate that NO enhanced AfaE and AfaD mediated virulence and play an important role in Dr/Afa + E. coli gestational tropism.

Pathogenesis of Human Diffusely Adhering Escherichia coli Expressing Afa/Dr Adhesins (Afa/Dr DAEC): Current Insights and Future Challenges

“…Comparing LPS responder (C3H/HeN) and nonresponder (C3H/HeJ) mice and Dr adhesin-positive E. coli and P fimbria-positive E. coli infections, Nowicki et al (403) observed that the infection level in the Dr-positive E. coli-infected C3H/HeN group treated with an inhibitor of NO, nitro-L-arginine methyl ester (L-NAME), was about 100-fold higher than that in the P adhesin-positive E. coli-infected, L-NAME-treated group. Dr adhesin-positive E. coli infection in mice (403) and AfaE/AfaD adhesin subunit-positive E. coli infection in rats (404) are followed by complications in pregnancy and death. Moreover, the death rate was increased by treatment with the NO blocker L-NAME in both mice and rat (403,404).…”

“…Dr adhesin-positive E. coli infection in mice (403) and AfaE/AfaD adhesin subunit-positive E. coli infection in rats (404) are followed by complications in pregnancy and death. Moreover, the death rate was increased by treatment with the NO blocker L-NAME in both mice and rat (403,404). As indicated above for Dr adhesininduced pyelonephritis in the mouse model, the role of the mouse DAF in Dr adhesin-induced complications during pregnancy in the rat model is intriguing, considering that the rodent DAF is clearly not recognized by Afa/Dr adhesins (254).…”

Role of Maternal Infections and Inflammatory Responses on Craniofacial Development

“…A subset of the cohort in the same study also exhibited an abundance of Peptostreptococcus anaerobius and associated shorter term pregnancies and newborns with lower length for age Z-score [ 159 ]. A study using pregnant rats showed that the weights of placenta and the offspring from rats infected with Escherichia coli (observed as a co-colonizer with Lactobacilli ) were significantly lower as compared to the non-infected controls [ 160 ]. Bacterial dysbiosis in the lower genital tract of pregnant females commonly results in bacterial vaginosis.…”

Response to the letter regarding the article: Association Between Perinatal Hypoxic-Ischemic Conditions and Attention-Deficit Hyperactivity Disorder (ADHD): A Meta-analysis

“…2 In addition to N 2 O, other ADHD risk factors could also influence NO synthesis in both mother and fetus. 6 –9 For example, the endothelial nitric oxide synthase (eNOS) activity in fetal umbilical veins decreased by 40% during exposure to maternal smoking. 6 Moreover, chronic alcohol decreased uterine arterial eNOS expression and altered its activated state that is characterized by multisite phosphorylation.…”