Bacteria predominantly exist as members of surfaced-attached communities known as biofilms. Many bacterial species initiate biofilms and adhere to each other using cell surface adhesins. This is the case for numerous ecologically diverse Alphaprotebacteria, which use polar exopolysaccharide adhesins for cell-cell adhesion and surface attachment. Here, we show that Rhodopseudomonas palustris, a metabolically versatile member of the alphaproteobacterial order Rhizobiales, contains a functional unipolar polysaccharide (UPP) biosynthesis gene cluster. Deletion of genes predicted to be critical for UPP biosynthesis and export abolished UPP production. We also found that R. palustris uses UPP to mediate biofilm formation across diverse photoheterotrophic growth conditions, wherein light and organic substrates are used to support growth. However, UPP was less important for biofilm formation during photoautotrophy, where light and CO 2 support growth, and during aerobic respiration with organic compounds. Expanding our analysis beyond R. palustris, we examined the phylogenetic distribution and genomic organization of UPP gene clusters among Rhizobiales species that inhabit diverse niches. Our analysis suggests that UPP is a conserved ancestral trait of the Rhizobiales but that it has been independently lost multiple times during the evolution of this clade, twice coinciding with adaptation to intracellular lifestyles within animal hosts.IMPORTANCE Bacteria are ubiquitously found as surface-attached communities and cellular aggregates in nature. Here, we address how bacterial adhesion is coordinated in response to diverse environments using two complementary approaches. First, we examined how Rhodopseudomonas palustris, one of the most metabolically versatile organisms ever described, varies its adhesion to surfaces in response to different environmental conditions. We identified critical genes for the production of a unipolar polysaccharide (UPP) and showed that UPP is important for adhesion when light and organic substrates are used for growth. Looking beyond R. palustris, we performed the most comprehensive survey to date on the conservation of UPP biosynthesis genes among a group of closely related bacteria that occupy diverse niches. Our findings suggest that UPP is important for free-living and plantassociated lifestyles but dispensable for animal pathogens. Additionally, we propose guidelines for classifying the adhesins produced by various Alphaprotebacteria, facilitating future functional and comparative studies.KEYWORDS Rhodopseudomonas, adhesin, biofilm, holdfast, phylogenetic analysis, unipolar polysaccharide
CDHR3 + Ciliated Cells Role of CDHR3 in HRV-C15 infection of differentiated primary airway epithelium Coding variant association with CDHR3 gene expression, HRV-C15 infection, and asthma hospitalization CDHR3 CRISPR Knockout Cells CDHR3 rs6967330 [GG] CDHR3 rs6967330 [AA] CDHR3 HRV-C15 Infection HRV-C15 Infection HRV-C15 Infection CDHR3 gene expression CDHR3 gene expression HRV-C15 Infection Asthma-induced hospitalization in minority children CDHR3 Abbreviations CDHR3: Cadherin-related family member 3; HRV-C15: Human Rhinovirus species C15 and childhood asthma exacerbations Background: Research in transformed immortalized cell lines indicates the cadherin-related family member 3 (CDHR3) protein serves as a receptor for human rhinovirus (HRV)-C. Similar experiments indicate that the CDHR3 coding variant rs6967330 increases CDHR3 protein surface expression. Objective: We sought to determine whether CDHR3 is necessary for HRV-C infection of primary airway epithelial cells (AECs) and to identify molecular mechanisms by which CDHR3 variants confer risk for asthma exacerbations. Methods: CDHR3 function and influence on HRV-C infection were investigated by using single-cell transcriptomics, CRISPR-Cas9 gene knockout, and genotype-specific donor experiments performed in primary AECs. Nasal airway epithelium cisexpression quantitative trait locus (eQTL) analysis of CDHR3 From a the Center for Genes,
Carbonic anhydrase inhibitors (CAIs) have been used for many decades in the treatment of glaucoma. Systemic CAIs were an early treatment option to lower intraocular pressure by reducing aqueous humour production; however, frequent side effects including polyuria and paresthesia contributed to the eventual development of topical CAIs. As topical drug development evolved over time, prostaglandin analogues and beta-blockers have become the gold standard of glaucoma therapies. Although prescribed less often than other classes of topical glaucoma therapies, topical CAIs continue to be used in combination therapies with beta-blockers and alpha agonists. Topical CAIs have also been demonstrated to alter biomarkers of ocular haemodynamics, which have relevance in glaucoma. The purpose of this review is to review and summarise the current state of topical CAI prescribing trends, known efficacy and suggested mechanisms and potential influence on ocular haemodynamics for the future of glaucoma management.
Precis: Although the XEN stent offers a lower risk of hypotony and choroidal effusions with fewer clinic visits postoperatively, its surgical success rate was inferior to the EX-PRESS shunt.Purpose: To compare the clinical efficacy and safety outcomes of the XEN stent and EX-PRESS glaucoma drainage device in glaucomatous eyes.Materials and Methods: One hundred eyes from 88 patients underwent ab interno XEN stent or EX-PRESS shunt implantation (52 XEN and 48 EX-PRESS) for uncontrolled glaucoma at the University of Colorado Eye Center. The primary outcome was surgical success defined as intraocular pressure (IOP) ≥ 6 and ≤ 18 mm Hg, without reoperation for uncontrolled glaucoma, loss of light perception, or use of glaucoma medications (complete success). Secondary outcomes were the same requirements allowing for medications (qualified success), mean IOP, medication use, adverse events, and number of postoperative clinic visits in the first 3 months.Results: Baseline characteristics including glaucoma type and severity were similar between groups, with the exception of XEN patients having fewer men (17% vs. 46%), older patients (median age, 78 vs. 68), and a higher percentage of white patients (89% vs. 69%). Adjusted hazard ratio of failure of XEN relative to EX-PRESS was 3.94 (95% confidence interval, 1.73-9.00, P = 0.001) for complete success and 1.61 (95% confidence interval, 0.40-6.38, P = 0.501) for qualified success. There were significantly fewer postoperative clinic visits during the first 3 months in the XEN group (5.3 vs. 9.1 visits, P < 0.001). The incidence of serous choroidal effusions and hypotony was significantly less after XEN compared with EX-PRESS (1 vs. 9, P = 0.02 and 15 vs. 25, P = 0.023, respectively). Three XEN stents (5.8%) required removal. Conclusions:In this population, although the XEN stent offers a better safety profile and fewer postoperative clinic visits, complete surgical success was inferior to the EX-PRESS shunt.
The bacterial flagellum is one of the most complex and sophisticated externalized structures that bacteria produce. Flagellar biosynthesis genes in bacteria are under hierarchical regulation, resulting in morphogenetic control of flagellum assembly (Chevance & Hughes, 2008;Soutourina & Bertin, 2003). The proper temporal and stoichiometric control of flagellar biogenesis dictates the insideout assembly of flagella and provides checkpoints to ensure that the requisite flagellar components are produced in sufficient quantities (Chevance & Hughes, 2017). Based on the best-studied systems in Escherichia coli and Salmonella enterica as models, the top genes of the hierarchy (class I) encode transcription factors that activate the expression of genes specifying the flagellar machinery components (class II; Kawagishi et al., 1992). Class II genes encode proteins that make up the hook-basal body complex of the flagellum. The basal body includes the type III secretion system that exports hook and filament proteins outside of the cell for filament assembly and the torque-generating motor proteins required for filament rotation.Assembly of the basal body permits class II proteins to activate the expression of class III genes (Chevance & Hughes, 2008). In the Gammaproteobacteria (such as E. coli, S. enterica, and Pseudomonas aeruginosa) and the Gram-positive bacterium Bacillus subtilis, class II genes encode the entire hook-basal body complex, and class III
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