Norepinephrine augmented in vitro growth of uropathogenic E. coli in Type 2 diabetes mellitus and its suppression by silodosin (alpha blocker) ☆,☆☆ Dinesh Prasad Gond a , Shivendra Singh b , N.K. Agrawal a, ⁎ a Department of Endocrinology and Metabolism, Institute of Medical Sciences Banaras Hindu University Varanasi, India b Department of Nephrology, Institute of Medical Sciences Banaras Hindu University Varanasi, India abstract article info Article history: Received 28 April 2017 Received in revised form 16 March 2018 Accepted 6 May 2018 Available online xxxx Keywords: Norepinephrine Silodosin Type 2 diabetes Urinary tract infection Uropathogenic E. coli Norepinephrine is secreted under conditions of stress in humans. The ability of bacteria to sense mammalian hormone may have a role in propagation of infection. The present study investigated the effect of norepinephrine on in vitro growth of uropathogenic E. coli (UPEC) and the effect of silodosin on norepinephrine-induced changes. The spot urine samples were collected from 56 individuals (14 diabetic patients with UTI, 14 diabetic without UTI, 14 non-diabetic UTI and 14 healthy volunteer controls) for the measurement of urinary norepinephrine concentrations. The concentration of norepinephrine, as found in urine of human subjects, was reproduced in artificial urine medium to study the growth of UPEC. The norepinephrine concentration showing maximum growth response was selected to study the effect of silodosin on the growth inhibition of UPEC. Result showed significantly elevated urinary norepinephrine in diabetic patients with and without UTI and also in nondiabetic UTI groups. The norepinephrine concentration equivalent to that in diabetic UTI patients enhanced the growth of UPEC. Furthermore, silodosin (0.32 μM) inhibited the growth of the UPEC. © 2018 Elsevier Inc. All rights reserved. 1. Introduction Diabetes mellitus (DM) is the most common endocrine disorder that affects more than 415 million people all over the world; India (76.04 mil- lion) has second largest number of diabetic patients in the world (International Diabetes Federation, 2015). Diabetes mellitus is associated with a higher risk of infections. The urinary tract infection (UTI) is the most common infection in diabetes. The prevalence of UTI and its recur- rence is 3 to 4 times higher in diabetic patients in comparison to nondia- betics (Fu et al., 2014; Geerlings, 2008; Hirji et al., 2012). In addition, the complications of UTI such as emphysematous cystitis, pyelonephritis, renal or perinephric abscess, bacteremia, and renal papillary necrosis are also more common in diabetic patients (Griffin et al., 1995; Huang and Tseng, 2000; Mnif et al., 2013). Immune dysfunction, glycosuria, voiding dysfunction and urinary retention, generally found in diabetes, may in- crease the susceptibility to UTI (Delamaire et al., 1997; Geerlings and Hoepelman, 1999; Geerlings et al., 1999; Hosking et al., 1978; Truzzi et al., 2008). However, the exact mechanism for higher risk of UTI in diabe- tes is not well understood. Many studies have described an association between stress and susceptibility towards infection. Stress hormone catecholamines (epinephrine and norepinephrine) modulate immunological defense against infection and induce growth in various gram-negative and gram-positive bacteria (Belay et al., 2003; Lyte and Ernst, 1992; Peterson et al., 1991). In addition, norepinephrine (NE) can also influence production of virulence factors such as toxins and adhesions, biofilm production of various gut related bacteria (Bansal et al., 2007; Dowd, 2007; Karavolos et al., 2008, 2011; Lyte et al., 1997; Sandrini et al., 2015). Studies have also documented that mammalian α adrener- gic receptor blockers suppress NE-induced growth and virulence factors (Freestone et al., 2007). Diabetes has life changing consequences for af- fected individuals, as evidenced by higher rates of anxiety and depres- sion (Anderson et al., 2001; Collins et al., 2009). Studies have reported that people with anxiety and depression have elevated urinary NE (Grossman and Potter, 1999; Hughes et al., 2004). The findings suggest higher probability of urinary NE in diabetic patients and it may play a role in progression of UTI in diabetic population. The objectives of this study were to measure urinary NE concentrations in UTI patients, to study the in vitro growth pattern of uropathogenic E. coli (UPEC) in the presence of these pathological concentrations of NE and to investi- gate the activity of silodosin (α adrenergic receptor blockers) on the NE-induced effect. Diagnostic Microbiology and Infectious Disease xxx (2018) xxx–xxx ☆ Conflict of interest: No conflict of interest. ☆☆ Financial support: University Grant Commission, New Delhi. ⁎ Corresponding author. Tel.: + 91-9415224741 (Mobile); fax: + 91-5422367568. E-mail address: drnkavns@gmail.com (N.K. Agrawal). DMB-14592; No of Pages 5 https://doi.org/10.1016/j.diagmicrobio.2018.05.005 0732-8893/© 2018 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Diagnostic Microbiology and Infectious Disease journal homepage: www.elsevier.com/locate/diagmicrobio Please cite this article as: Gond DP, et al, Norepinephrine augmented in vitro growth of uropathogenic E. coli in Type 2 diabetes mellitus and its suppression by silodosin (al..., Diagn Microbiol Infect Dis (2018), https://doi.org/10.1016/j.diagmicrobio.2018.05.005