Highlights d Contractile injection systems are syringe-like structures from bacteria d A contractile injection system called MACs targets insect and mouse cell lines d MACs kill cell lines by delivering an effector called Pne1 with nuclease activity

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24Many bacteria interact with target organisms using syringe-like structures called 25 Contractile Injection Systems (CIS). CIS structurally resemble headless bacteriophages 26 and share evolutionarily related proteins such as the tail tube, sheath, and baseplate 27 complex. Recent evidence shows that CIS are specialized to puncture membranes and 28 often deliver effectors to target cells. In many cases, CIS mediate trans-kingdom 29 interactions between bacteria and eukaryotes, however the effectors delivered to target 30 cells and their mode of action are often unknown. In this work, we establish an in vitro 31 model to study a CIS called Metamorphosis Associated Contractile structures (MACs) 32 that target eukaryotic cells. We show that MACs kill two eukaryotic cell lines, Fall 33Armyworm Sf9 cells and J774A.1 murine macrophage cells through the action of a 34 newly identified MAC effector, termed Pne1. To our knowledge, Pne1 is the first CIS 35 effector exhibiting nuclease activity against eukaryotic cells. Our results define a new 36 mechanism of CIS-mediated bacteria-eukaryote interaction and are a first step toward 37 understanding structures with the potential to be developed as novel delivery systems 38 for eukaryotic hosts. 39 40 63 targeting eukaryotic cells are yet described that possess nuclease activity. 64 65One group of evolutionarily related CIS have been shown to mediate interactions with 66 diverse eukaryotic organisms including amoeba, grass grubs, wax moths and wasps 67 (Böck et al., 2017; Hurst et al., 2007; Penz et al., 2012 Penz et al., , 2010 Sarris et al., 2014; Yang 68 et al., 2006). We recently described a related eCIS mediating the beneficial relationship 69 between the Gram-negative bacterium Pseudoalteramonas luteoviolacea and a marine 70 tubeworm, Hydroides elegans, hereafter Hydroides (Shikuma et al., 2014(Shikuma et al., , 2016. We 71 called this eCIS from P. luteoviolacea MACs for Metamorphosis Associated Contractile 72 structures, because they stimulate the metamorphosis of Hydroides (Shikuma et al., 73 2014). MACs are the first CIS discovered to form arrays of phage tail-like structures 74 composed of about 100 tails and often measure about 1 µm in diameter. While MACs 75 provide another example of CIS-eukaryote interactions, the range of hosts targeted by 76 eCIS like MACs as well as the identity and mode of action of effectors that mediate 77 these interactions remain poorly understood. 78 79To study the interaction between MACs and eukaryotic cells, we establish an in vitro 80 CIS-cell line interaction model with insect and mammalian cell types. Using these 81 systems, we identify a new MAC effector with nuclease activity that is responsible for 82 cytotoxicity in both cell types. Our results indicate that MACs can interact with a range 83 of host cells and a specific effector mediates killing of eukaryotic cells. 84 85 RESULTS 86 MACs kill insect cell lines in vitro. To study MACs from P. luteoviolacea and test their 87 effect on eukaryotic cells, we focused ...

Current research suggests COVID-19 in pregnancy is associated with poor maternal and fetal outcomes, although the exact mechanisms remain unclear, and the approach to the management of affected patients presents a distinct challenge to clinicians. We present a case of gestational hypertension, eclampsia, and postpartum depression in a 39-year-old gravida 4, para 0030 (G4P0) pregnant patient following multiple prenatal severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infections. After a case of coronavirus disease-19 (COVID-19) during her first trimester, the patient received a two-dose mRNA vaccine against SARS-CoV-2. Despite vaccination, she again contracted COVID-19 during her third trimester of pregnancy. She subsequently developed gestational hypertension at 38 weeks necessitating a cesarean section at 38+4 weeks. The patient delivered a healthy neonate, however, her postpartum course was complicated by eclampsia and postpartum depression. This case bolsters current literature and emphasizes the necessity of continued research into the effects of COVID-19 in pregnant and postpartum women.