Streptococcus pneumoniae is an ovoid-shaped Gram-positive bacterium that grows by carrying out peripheral and septal peptidoglycan (PG) synthesis, analogous to model bacilli, such as Escherichia coli and Bacillus subtilis. In the model bacilli, FtsZ and FtsA proteins assemble into a ring at midcell and are dedicated to septal PG synthesis but not peripheral PG synthesis; hence, inactivation of FtsZ or FtsA results in long filamentous cells unable to divide. Here, we demonstrate that FtsA and FtsZ colocalize at midcell in S. pneumoniae and that partial depletion of FtsA perturbs septum synthesis, resulting in elongated cells with multiple FtsZ rings that fail to complete septation. Unexpectedly, complete depletion of FtsA resulted in the delocalization of FtsZ rings and ultimately cell ballooning and lysis. In contrast, depletion or deletion of gpsB and sepF, which in B. subtilis are synthetically lethal with ftsA, resulted in enlarged and elongated cells with multiple FtsZ rings, with deletion of sepF mimicking partial depletion of FtsA. Notably, cell ballooning was not observed, consistent with later recruitment of these proteins to midcell after Z-ring assembly. The overproduction of FtsA stimulates septation and suppresses the cell division defects caused by the deletion of sepF and gpsB under some conditions, supporting the notion that FtsA shares overlapping functions with GpsB and SepF at later steps in the division process. Our results indicate that, in S. pneumoniae, both GpsB and SepF are involved in septal PG synthesis, whereas FtsA and FtsZ coordinate both peripheral and septal PG synthesis and are codependent for localization at midcell.IMPORTANCE Streptococcus pneumoniae (pneumococcus) is a clinically important human pathogen for which more therapies against unexploited essential targets, like cell growth and division proteins, are needed. Pneumococcus is an ovoid-shaped Gram-positive bacterium with cell growth and division properties that have important distinctions from those of rod-shaped bacteria. Gaining insights into these processes can thus provide valuable information to develop novel antimicrobials. Whereas rods use distinctly localized protein machines at different cellular locations to synthesize peripheral and septal peptidoglycans, we present evidence that S. pneumoniae organizes these two machines at a single location in the middle of dividing cells. Here, we focus on the properties of the actin-like protein FtsA as an essential orchestrator of peripheral and septal growth in this bacterium.KEYWORDS FtsA, Gram-positive cocci, Streptococcus pneumoniae, cell division

Objectives This randomized, controlled, pilot study assessed the outcome of non-surgical primary/secondary root canal treatments either with a novel bioactive sealer and the single-cone technique or with gutta-percha, zinc oxide-eugenol sealer (ZOE), and warm vertical compaction. Materials and methods Sixty-nine patients were randomly divided into two groups that were treated using the single-cone technique with BioRootTM RCS (Septodont) (BIO group) or warm vertical compaction with gutta-percha and ZOE sealer (PCS group). Two subsamples (BIOAP and PCSAP) comprised the cases with apical periodontitis. Treatment was undertaken by four residents using a standardized instrumentation and disinfection protocol. The periapical index (PAI) was recorded, and clinical and radiographic follow-up performed at 1, 3, 6, and 12 months. Treatment success was assessed according to “periapical healing” and “tooth survival”. The test for the equality of proportions, t tests for the equality of means, and non-parametric K-sample tests for the equality of medians were applied when appropriate. Results The survival rate was similar in the BIO and PCS (p = 0.4074) and the BIOAP and PCSAP groups (p = 0.9114). The success rate was higher in the BIO groups, but not statistically significant (p = 0.0735). In both BIOAP and PCSAP groups, a progressive decrease in the PAI was observed. Conclusion At 12 months, both techniques showed reliable results. Further studies and longer follow-ups are needed. Clinical relevance This study documents the feasibility of using a bioactive sealer in conjunction with the single-cone technique to obturate the root canal and obtaining a predictable outcome. Trial registration ClinicalTrials.gov Identifie: NCT04249206

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Various aryl 1-pyrryl sulfones were synthesized and tested as inhibitors of HIV-1. 2-Nitrophenyl-2-ethoxycarbonyl-1-pyrryl sulfone, the most active among test derivatives, was selected as lead compound of the aryl pyrryl sulfone series. The in vitro anti-HIV-1 activity and cytotoxicity of 41 compounds is reported. Some structure-activity relationships are discussed also in comparison with the known NPPS (2-nitrophenyl phenyl sulfone).

Biologic medications (BMs) are increasingly used for the management of systemic chronic inflammatory diseases. These diseases are often associated with a higher prevalence of apical periodontitis (AP) and periodontitis (P). The purpose of this systematic review was to ascertain the interactions between AP and/or P and BMs. The review was registered in the PROSPERO database (CRD42017054756). Electronic searches were performed on Pubmed Medline, Scopus and The Web of Science from their inception through to 20 March 2018. The references of the articles selected were checked. The keywords were chosen based on a pilot search, which aimed to find the most frequently prescribed BMs. The included studies were appraised qualitatively using appropriate tools. Thirty-five articles met the inclusion criteria, comprising 16 non-randomized clinical studies, 12 in vivo animal studies and 7 case reports. Quality of information was assessed as high in 18 articles, moderate in 16 articles and low in 1 article. BMs in patients suffering from chronic inflammatory diseases seems to inhibit the progression of AP and P, and to enhance the healing response to periodontal and endodontic treatment. A healthier condition of the periodontal tissues seems to be associated with a better response of the patient to BMs therapy.Abbreviations and acronyms: AP = apical periodontitis; BM = biologic medications; P = periodontitis; RANKL = receptor activator of nuclear factor kappa-Β ligand (RANKL).