Cytomegalovirus (CMV) seroprevalence among women at childbearing age, maternal and congenital CMV infection: policy implications of a descriptive, retrospective, community-based study.

BACKGROUND: Maternal CMV infection during pregnancy, either primary or non-primary, may be associated with fetal infection and long-term sequelae. While guidelines recommend against it, screening for CMV in pregnant women is a prevalent clinical practice in Israel. Our aim is to provide updated, local, clinically relevant, epidemiological information about CMV seroprevalence among women at childbearing age, the incidence of maternal CMV infection during pregnancy and the prevalence of congenital CMV (cCMV), as well as to provide information about the yield of CMV serology testing. METHODS: We performed a descriptive, retrospective study of women at childbearing age who were members of Clalit Health Services in the district of Jerusalem and had at least one gestation during the study period (2013-2019). We utilized serial serology tests to determine CMV serostatus at baseline and at pre/periconception and identified temporal changes in CMV serostatus. We then conducted a sub-sample analysis integrating inpatient data on newborns of women who gave birth in a single large medical center. cCMV was defined as either positive urine CMV-PCR test in a sample collected during the first 3 weeks of life, neonatal diagnosis of cCMV in the medical records, or prescription of valganciclovir during the neonatal period. RESULTS: The study population Included 45,634 women with 84,110 associated gestational events. Initial CMV serostatus was positive in 89% women, with variation across different ethno-socioeconomic subgroups. Based on consecutive serology tests, the detected incidence rate of CMV infection was 2/1000 women follow-up years, among initially seropositive women, and 80/1000 women follow-up years, among initially seronegative women. CMV infection in pregnancy was identified among 0.2% of women who were seropositive at pre/periconception and among 10% of women who were seronegative. In a subsample, which included 31,191 associated gestational events, we identified 54 newborns with cCMV (1.9/1000 live births). The prevalence of cCMV among newborns of women who were seropositive at pre/periconception was lower than among newborns of women who were seronegative (2.1 vs. 7.1/1000). Frequent serology tests among women who were seronegative at pre/periconception detected most primary CMV infections in pregnancy that resulted in cCMV (21/24). However, among women who were seropositive, serology tests prior to birth detected none of the non-primary infections that resulted in cCMV (0/30). CONCLUSIONS: In this retrospective community-based study among women of childbearing age characterized by multiparity and high seroprevalence of CMV, we find that consecutive CMV serology testing enabled to detect most primary CMV infections in pregnancy that led to cCMV in newborns but failed to detect non-primary CMV infections in pregnancy. Conducting CMV serology tests among seropositive women, despite guidelines' recommendations, has no clinical value, while it is costly and introduces further uncertainties and distress. We thus recommend against routine CMV serology testing among women who were seropositive in a prior serology test. We recommend CMV serology testing prior to pregnancy only among women known to be seronegative or women whose serology status is unknown.

The SOS response is permitted in Escherichia coli strains deficient in the expression of the mazEF pathway.

The Escherichia coli (E. coli) SOS response is the largest, most complex, and best characterized bacterial network induced by DNA damage. It is controlled by a complex network involving the RecA and LexA proteins. We have previously shown that the SOS response to DNA damage is inhibited by various elements involved in the expression of the E. coli toxin-antitoxin mazEF pathway. Since the mazEF module is present on the chromosomes of most E. coli strains, here we asked: Why is the SOS response found in so many E. coli strains? Is the mazEF module present but inactive in those strains? We examined three E. coli strains used for studies of the SOS response, strains AB1932, BW25113, and MG1655. We found that each of these strains is either missing or inhibiting one of several elements involved in the expression of the mazEF-mediated death pathway. Thus, the SOS response only takes place in E. coli cells in which one or more elements of the E. coli toxin-antitoxin module mazEF or its downstream pathway is not functioning.

Apoptosis-like death, an extreme SOS response in Escherichia coli.

In bacteria, SOS is a global response to DNA damage, mediated by the recA-lexA genes, resulting in cell cycle arrest, DNA repair, and mutagenesis. Previously, we reported that Escherichia coli responds to DNA damage via another recA-lexA-mediated pathway resulting in programmed cell death (PCD). We called it apoptosis-like death (ALD) because it is characterized by membrane depolarization and DNA fragmentation, which are hallmarks of eukaryotic mitochondrial apoptosis. Here, we show that ALD is an extreme SOS response that occurs only under conditions of severe DNA damage. Furthermore, we found that ALD is characterized by additional hallmarks of eukaryotic mitochondrial apoptosis, including (i) rRNA degradation by the endoribonuclease YbeY, (ii) upregulation of a unique set of genes that we called extensive-damage-induced (Edin) genes, (iii) a decrease in the activities of complexes I and II of the electron transport chain, and (iv) the formation of high levels of OH˙ through the Fenton reaction, eventually resulting in cell death. Our genetic and molecular studies on ALD provide additional insight for the evolution of mitochondria and the apoptotic pathway in eukaryotes. Importance: The SOS response is the first described and the most studied bacterial response to DNA damage. It is mediated by a set of two genes, recA-lexA, and it results in DNA repair and thereby in the survival of the bacterial culture. We have shown that Escherichia coli responds to DNA damage by an additional recA-lexA-mediated pathway resulting in an apoptosis-like death (ALD). Apoptosis is a mode of cell death that has previously been reported only in eukaryotes. We found that E. coli ALD is characterized by several hallmarks of eukaryotic mitochondrial apoptosis. Altogether, our results revealed that recA-lexA is a DNA damage response coordinator that permits two opposite responses: life, mediated by the SOS, and death, mediated by the ALD. The choice seems to be a function of the degree of DNA damage in the cell.