Spa33, a Cell Surface-Associated Subunit of the Mxi-Spa Type III Secretory Pathway of Shigella flexneri, Regulates Ipa Protein Traffic

The Mxi-Spa type III secretion system of Shigella flexneri directs the host cell contact-induced secretion of a set of invasins, referred to as Ipas. In this study, we examined the role of Spa33 in Ipa secretion. A spa33-null mutant was both noninvasive and unable to translocate the Ipas from inner membrane to outer membrane (OM) positions of the Mxi-Spa transmembrane channel. Spa33 was found to be a Mxi-Spa substrate that is translocated to the bacterial cell surface upon the induction of Ipa secretion. This mobility may serve to drive Ipa translocation within Mxi-Spa toward OM positions. Consistent with a second distinct role in regulating Ipa traffic, the overexpression of Spa33 also blocked Ipa secretion and resulted in Ipa accumulation at the OM. Co-overexpression of Spa33 and another OM-associated element, Spa32, did not disrupt Ipa secretion, suggesting an interaction between the two proteins and an effect on the mechanism which serves to regulate Ipa release from the OM. These findings indicate that Spa33 is a mobile element within Mxi-Spa, which is required to control Ipa translocation into and out of OM positions of the secretory structure

The development of a FACS-based strategy for the isolation of Shigella flexneri mutants that are deficient in intercellular spread.

In the disease course of bacillary dysentery, pathogenic Shigella flexneri invade colonic epithelial cells and spread both within and between host cells. The ability to spread intercellularly allows the organism to infect an entire epithelial layer without significant contact with the extracellular milieu. Using fluorescence activated cell sorter (FACS)-based technology, we developed a rapid and powerful selection strategy for the isolation of S. flexneri mutants that are unable to spread from cell to cell. The majority of mutants identified using this strategy harbour mutations that affect the structure of their lipopolysaccharide or the ability of the bacteria to move intracellularly via actin-based motility; both factors have previously been shown to be essential for cell-to-cell spread. However, using a modified strategy that eliminated both of these types of mutants, we identified several mutants that provide us with evidence that bacterial proteins of the type III secretion system, which are essential for bacterial entry into host cells, also play a role in cell-to-cell spread.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe

Delivery outcomes in the subsequent pregnancy following the conservative management of placenta accreta spectrum disorder: A systematic review and meta-analysis

Objective:Cesarean hysterectomy is generally presumed to decrease maternal morbidity and mortality secondary to placenta accreta spectrum disorder (PAS). Recently, uterine-sparing techniques have been introduced in conservative management of PAS to preserve fertility and potentially reduce surgical complications. However, despite often expressing the intention for future conception, few data are available regarding the subsequent pregnancy outcome after conservative management of PAS. Thus, we aimed to perform a systematic review and meta-analysis to assess the subsequent pregnancy outcomes following conservative management of PAS. Data sources:PubMed, Scopus, and Web of Science databases were searched from inception to September 2022. Study eligibility criteria:We included all studies, with the exception of case studies, that reported the first subsequent pregnancy outcomes in individuals with a previous history of PAS who underwent any type of conservative management. Study appraisal and synthesis method:The R programming language with the meta package was used. The random effects model and inverse variance method were used to pool the proportion of pregnancy outcomes. Results:We identified five studies involving 1,458 subjects that were eligible for quantitative synthesis. The type of conservative management included placenta left in situ (n=1), resection surgery (n=1), and not reported in three studies. The PAS recurrence rate in the subsequent pregnancy was 11.8% (95% CI: 1.1-60.3, I2 = 86.4%), and 1.9% (95% CI: 0.0-34.1, I2 = 82.4%) underwent Cesarean hysterectomy. Postpartum hemorrhage occurred in 10.3% (95% CI: 0.3-81.4, I2 = 96.7%). A composite adverse maternal outcome was reported in 22.7% of subjects (95% CI: 0.0-99.4, I2 = 56.3%). Conclusion:Favorable pregnancy outcome is possible following successful conservation of the uterus in a PAS pregnancy. Approximately one out of four subsequent pregnancies following conservative management of PAS experienced significant adverse maternal outcomes. Given such high incidence of adverse outcomes and morbidity, patient and provider preparation is vital when managing this population