Diarrheagenic enteroaggregative Escherichia coli causing urinary tract infection and bacteremia leading to sepsis

We report a case of a 55-year-old immunocompromised female who presented to the emergency department with severe diarrhea and vomiting following travel to the Philippines. Stool bacteriology revealed a mixed infection involving an enteropathogenic Escherichia coli and two distinct strains of enteroaggregative Escherichia coli (EAEC). During hospitalization, urine and blood culture tested positive for one of the diarrheagenic EAEC strains, necessitating urinary catheterization, intensive care, and antimicrobial treatment with trimethoprim-sulfamethoxazole, followed by meropenem. Although known to occasionally cause urinary tract infections, EAEC have not been previously associated with sepsis. Our report highlights the potential of EAEC to cause severe extraintestinal infections

High-Level Production of the Industrial Product Lycopene by the Photosynthetic Bacterium Rhodospirillum rubrum

The biosynthesis of the major carotenoid spirilloxanthin by the purple nonsulfur bacterium Rhodospirillum rubrum is thought to occur via a linear pathway proceeding through phytoene and, later, lycopene as intermediates. This assumption is based solely on early chemical evidence (B. H. Davies, Biochem. J. 116:93–99, 1970). In most purple bacteria, the desaturation of phytoene, catalyzed by the enzyme phytoene desaturase (CrtI), leads to neurosporene, involving only three dehydrogenation steps and not four as in the case of lycopene. We show here that the chromosomal insertion of a kanamycin resistance cassette into the crtC-crtD region of the partial carotenoid gene cluster, whose gene products are responsible for the downstream processing of lycopene, leads to the accumulation of the latter as the major carotenoid. We provide spectroscopic and biochemical evidence that in vivo, lycopene is incorporated into the light-harvesting complex 1 as efficiently as the methoxylated carotenoids spirilloxanthin (in the wild type) and 3,4,3′,4′-tetrahydrospirilloxanthin (in a crtD mutant), both under semiaerobic, chemoheterotrophic, and photosynthetic, anaerobic conditions. Quantitative growth experiments conducted in dark, semiaerobic conditions, using a growth medium for high cell density and high intracellular membrane levels, which are suitable for the conventional industrial production in the absence of light, yielded lycopene at up to 2 mg/g (dry weight) of cells or up to 15 mg/liter of culture. These values are comparable to those of many previously described Escherichia coli strains engineered for lycopene production. This study provides the first genetic proof that the R. rubrum CrtI produces lycopene exclusively as an end product

Targeting naproxen to non-parenchymal liver cells protects against endotoxin induced liver damage

Non-steroidal anti-inflammatory drugs (NSAID's) could be of value in the treatment of liver disease; however, their use in this situation is limited by renal side effects. Therefore, we explored whether naproxen covalently bound to human serum albumin (NAP-HSA) was able to reduce toxicity in an acute model of liver disease induced by endotoxin in rats pretreated with Corynebacterium parvum. In the isolated perfused liver of such animals endotoxin induced cholestasis (0.62 +/- 0.05 vs. 0.24 +/- 0.09 mu l.min(-1).g liver(-1); p <0.05), increased vascular resistance (11300 +/- 400 vs. 311000 +/- 2000 dyn.s.cm(-5) p <0.05) and alanine aminotransferase release (22 +/- 9 vs. 149 +/- 40 IU/I; p <0.05). A; the highest dose tested (22 mg/kg, corresponding to 6.0 mu moles naproxen), NAP-HSA normalized ALT release (21 +/- 10 IU/I; p <0.05) while an equimolar amount of non-targeted naproxen was only partially effective (56 +/- 19 IU/I). A conventional dose of naproxen similarly prevented transaminase release. Cholestasis and increased vascular resistance were also prevented by NAPHSA. Drug targeting by linking drugs to proteins is a potentially useful approach to maximizing drug effect while minimizing adverse events; this could be particularly useful for compounds with potentially serious adverse effects in patients with chronic liver disease such as the nonsteroidal anti-inflammatory agents used in the present study

Targeting naproxen to non-parenchymal liver cells protects against endotoxin induced liver damage

Non-steroidal anti-inflammatory drugs (NSAID's) could be of value in the treatment of liver disease; however, their use in this situation is limited by renal side effects. Therefore, we explored whether naproxen covalently bound to human serum albumin (NAP-HSA) was able to reduce toxicity in an acute model of liver disease induced by endotoxin in rats pretreated with Corynebacterium parvum. In the isolated perfused liver of such animals endotoxin induced cholestasis (0.62 +/- 0.05 vs. 0.24 +/- 0.09 mu l.min(-1).g liver(-1); p &lt;0.05), increased vascular resistance (11300 +/- 400 vs. 311000 +/- 2000 dyn.s.cm(-5) p &lt;0.05) and alanine aminotransferase release (22 +/- 9 vs. 149 +/- 40 IU/I; p &lt;0.05). A; the highest dose tested (22 mg/kg, corresponding to 6.0 mu moles naproxen), NAP-HSA normalized ALT release (21 +/- 10 IU/I; p &lt;0.05) while an equimolar amount of non-targeted naproxen was only partially effective (56 +/- 19 IU/I). A conventional dose of naproxen similarly prevented transaminase release. Cholestasis and increased vascular resistance were also prevented by NAPHSA. Drug targeting by linking drugs to proteins is a potentially useful approach to maximizing drug effect while minimizing adverse events; this could be particularly useful for compounds with potentially serious adverse effects in patients with chronic liver disease such as the nonsteroidal anti-inflammatory agents used in the present study.</p

Targeting naproxen coupled to human serum albumin to nonparenchymal cells reduces endotoxin-induced mortality in rats with biliary cirrhosis

Endotoxin is thought to play a major role in cirrhotic liver disease, Cyclo-oxygenase inhibitors were shown to be partially protective against endotoxin but cannot be used in cirrhotic patients because of renal side-effects, We argued that administration of naproxen (NAP) linked to human serum albumin (HSA), which results in specific delivery of NAP to endothelial cells (EC) and Kupffer cells (KC) and exhibited hepatoprotective effects against Lipopolysaccharide (LPS) in vitro, could protect cirrhotic rats from LPS toxicity while preserving renal function. The studies were performed in rats rendered cirrhotic by bile duct ligation (BDL); animals received LPS (Escherichia coli, 800 mu g/kg) intravenously. Five groups were studied: LPS alone, rats pretreated with a conventional dose of NAP (50 mg/kg), NAP-HSA (22 mg/kg), NAP equimolar to NAP-HSA (50 mg/kg), or the HSA carrier. LPS induced significant mortality (55%); this was not affected by equimolar NAP (57%) but accentuated by conventional NAP (88%), In contrast, NAP-HSA provided significant protection (9%; P <.05). After conventional NAP treatment, significant renal toxicity was observed as evidenced by a marked reduction in sodium excretion (LPS vs. NAP-HSA vs, NAP [SO mg/kg] 33 +/- 22 vs, 50 +/- 39 vs. 4 +/- 3 mu mol/h; P <.05). Renal prostaglandin E-2 (PGE(2)) excretion was reduced by NAP in all groups, but most markedly at the conventional dosage (LPS vs. NAP-HSA vs, NAP [50 mg/kg] 132 +/- 115 vs. 39 +/- 19 vs, 9 +/- 8 ng/mL; P <.05). Successful targeting was evidenced by a significant hepatic enrichment of NAP in the NAP-HSA group compared with the equimolar untargeted group (30.16 +/- 9.33 vs. 1.13 +/- 1.95 nmol/g liver). Thus, targeting NAP to EC/KC results in improved survival, higher efficacy, and sparing of renal function in cirrhotic rats

Targeting naproxen coupled to human serum albumin to nonparenchymal cells reduces endotoxin-induced mortality in rats with biliary cirrhosis

Endotoxin is thought to play a major role in cirrhotic liver disease, Cyclo-oxygenase inhibitors were shown to be partially protective against endotoxin but cannot be used in cirrhotic patients because of renal side-effects, We argued that administration of naproxen (NAP) linked to human serum albumin (HSA), which results in specific delivery of NAP to endothelial cells (EC) and Kupffer cells (KC) and exhibited hepatoprotective effects against Lipopolysaccharide (LPS) in vitro, could protect cirrhotic rats from LPS toxicity while preserving renal function. The studies were performed in rats rendered cirrhotic by bile duct ligation (BDL); animals received LPS (Escherichia coli, 800 mu g/kg) intravenously. Five groups were studied: LPS alone, rats pretreated with a conventional dose of NAP (50 mg/kg), NAP-HSA (22 mg/kg), NAP equimolar to NAP-HSA (50 mg/kg), or the HSA carrier. LPS induced significant mortality (55%); this was not affected by equimolar NAP (57%) but accentuated by conventional NAP (88%), In contrast, NAP-HSA provided significant protection (9%; P <.05). After conventional NAP treatment, significant renal toxicity was observed as evidenced by a marked reduction in sodium excretion (LPS vs. NAP-HSA vs, NAP [SO mg/kg] 33 +/- 22 vs, 50 +/- 39 vs. 4 +/- 3 mu mol/h; P <.05). Renal prostaglandin E-2 (PGE(2)) excretion was reduced by NAP in all groups, but most markedly at the conventional dosage (LPS vs. NAP-HSA vs, NAP [50 mg/kg] 132 +/- 115 vs. 39 +/- 19 vs, 9 +/- 8 ng/mL; P <.05). Successful targeting was evidenced by a significant hepatic enrichment of NAP in the NAP-HSA group compared with the equimolar untargeted group (30.16 +/- 9.33 vs. 1.13 +/- 1.95 nmol/g liver). Thus, targeting NAP to EC/KC results in improved survival, higher efficacy, and sparing of renal function in cirrhotic rats