LptD plays a specific role in alginate production. Our findings suggest that there are two pathways for the production of alginate in P. aeruginosa, one involving AlgW in the wild-type, and one involving AlgO in the mucA22 mutant.

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23Cystic fibrosis (CF) is a genetic disorder that leads to a buildup of mucus in the 24 lungs ideal for bacterial colonization. When Pseudomonas aeruginosa enters the 25 CF lung, it undergoes a conversion from nonmucoid to mucoid; colonization by a 26 mucoid strain of P. aeruginosa greatly increases mortality.The mucoid 27 phenotype is due to the production of alginate. 44. CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/319004 doi: bioRxiv preprint first posted online May. 10, 2018; 3 phenotype was restored in 28 of the 41 sap mutants when complemented with 45 plasmids harboring algT/U. Four of the sap mutants are complemented 46 by algO. Sequence analyses of the algT/U mutants have found no mutations in 47 the coding region or promoter leading to the hypothesis that there is another, as 48 yet unidentified mechanism of alginate regulation in this clinical strain. 49. CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/319004 doi: bioRxiv preprint first posted online May. 10, 2018; 4 INTRODUCTION 50Cystic fibrosis (CF) is the most common cause of death due to genetic disorder 51(1). CF is an autosomal recessive disorder caused by a mutation in the cystic 52 fibrosis transmembrane conductance regulator (cftr) gene (2-4). The most 53 common CF mutation (~90%) is the ΔF508 which is the deletion of three 54 nucleotides leading to the loss of a phenylalanine in the 508 position, and thus, a 55 defective protein (3). A wide range of other mutations are possible that lead to 56 either impaired function or total loss of activity (5). 57Ordinarily, CFTR functions as anion transporter (6). When mutated, normal anion 58 flow is restricted (7) and mucus accumulates in the CF lung; resulting pulmonary 59 failure is the foremost killer of CF patients (8, 9) The mucus buildup provides a 60 breeding ground for many pathogenic bacterial species especially S. aureus, H. The pathogen that rises to prominence over the life of a CF patient and is the 64 leading cause of mortality is P. aeruginosa (11, 12). 65P. aeruginosa expresses a multitude of virulence factors (13). The major 66 contributor to P. aeruginosa virulence in patients with CF is its ability to change 67 from the standard, non-mucoid form to the mucoid form (14, 15 80Alginate biosynthesis comes at a high metabolic cost, and thus is tightly regulated algT/U, codes for a sigma factor able to bind to RNA polymerase (RNAP), guiding 85 it to transcribe the genes necessary for alginate production (31, 32). 86Under normal circumstances, P. aeruginosa is non-mucoid, as is the case with the 87 prototypic reference strain, PAO1 (33). Upon colonizing...

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Background: Metformin for type 2 diabetes mellitus has more beneficial effect with few side effects like vitamin B12 deficiency. So, this study aimed to determine the level of vitamin B12 in patients with type 2 diabetes mellitus using metformin and its association with dose and duration of metformin use. Methods: This was descriptive, cross-sectional, hospital-based study. A total of 128 diabetic patients using metformin for more than 6 months were enrolled. After taking informed consent, considering exclusion criteria, level of serum B12 were quantified by chemiluminescent enzyme immunoassay. Vitamin B12 level <300pg/dl as inadequate and ≥300pg/dl as adequate; metformin 1000mg as low dose; more than 1000mg as high dose were considered. Also, metformin used 1000mg /day taken as constant and comparing it with duration of  > 10 years with duration of > 10 years. Data were entered in Microsoft Excel 2013 and analyzed on SPSS V25. Results: Our study results 62.5% had adequate (>300pmol/l) and 37.5% had inadequate (≤300pmol/l) vitamin B12 level in patients with type 2 diabetes using metformin. Level of vitamin B12 deficiency was statistically associated with increasing dose of metformin used (p<0.001) and long term used of metformin used (p<019). Conclusions: This study concluded that there is prevalence of deficiency of Vit B12 level in type 2 diabetes mellitus patients using metformin. Also, this deficiency level depends on use of dose of metformin.