Light Modulates Important Pathogenic Determinants and Virulence in ESKAPE Pathogens Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus.

Light sensing has been extensively characterized in the human pathogen Acinetobacter baumannii at environmental temperatures. However, the influence of light on the physiology and pathogenicity of human bacterial pathogens at temperatures found in warm-blooded hosts is still poorly understand. In this work, we show that Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa (ESKAPE) priority pathogens, which have been recognized by the WHO and the CDC as critical, can also sense and respond to light at temperatures found in human hosts. Most interestingly, in these pathogens, light modulates important pathogenicity determinants as well as virulence in an epithelial infection model, which could have implications in human infections. In fact, we found that alpha-toxin-dependent hemolysis, motility, and growth under iron-deprived conditions are modulated by light in S. aureus Light also regulates persistence, metabolism, and the ability to kill competitors in some of these microorganisms. Finally, light exerts a profound effect on the virulence of these pathogens in an epithelial infection model, although the response is not the same in the different species; virulence was enhanced by light in A. baumannii and S. aureus, while in A. nosocomialis and P. aeruginosa it was reduced. Neither the BlsA photoreceptor nor the type VI secretion system (T6SS) is involved in virulence modulation by light in A. baumannii Overall, this fundamental knowledge highlights the potential use of light to control pathogen virulence, either directly or by manipulating the light regulatory switch toward the lowest virulence/persistence configuration.IMPORTANCE Pathogenic bacteria are microorganisms capable of producing disease. Dangerous bacterial pathogens, such as Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii, are responsible for serious intrahospital and community infections in humans. Therapeutics is often complicated due to resistance to multiple antibiotics, rendering them ineffective. In this work, we show that these pathogens sense natural light and respond to it by modulating aspects related to their ability to cause disease; in the presence of light, some of them become more aggressive, while others show an opposite response. Overall, we provide new understanding on the behavior of these pathogens, which could contribute to the control of infections caused by them. Since the response is distributed in diverse pathogens, this notion could prove a general concept.

Therapeutic Efficacy and Safety of Undenatured Type II Collagen Singly or in Combination with Glucosamine and Chondroitin in Arthritic Dogs.

ABSTRACT This investigation was undertaken to evaluate the therapeutic efficacy and safety of glycosylated undenatured type II collagen (UC-II) alone or in combination with glucosamine HCl and chondroitin sulfate in arthritic dogs. Twenty dogs divided into four groups (n = 5) were daily treated orally for 120 days: group I, placebo; group II, 10 mg UC-II; group III, 2,000 mg glucosamine + 1,600 mg chondroitin; group IV, UC-II (10 mg) + glucosamine (2,000 mg) + chondroitin (1,600 mg), followed by a 30-day withdrawal period. On a monthly basis, dogs were examined for overall pain, pain upon limb manipulation, and exercise-associated lameness. Serum samples were analyzed for markers of liver function (ALT and bilirubin) and renal function (BUN and creatinine). Body weight was also measured at a monthly interval. Dogs in group I exhibited no change in arthritic conditions. Dogs receiving UC-II alone showed significant reductions in overall pain within 30 days (33%) and pain upon limb manipulation and exercise-associated lameness after 60 days (66% and 44%, respectively) of treatment. Maximum reductions in pain were noted after 120 days of treatment (overall pain reduction, 62%; pain reduction upon limb manipulation, 91%; and reduction in exercise-associated lameness, 78%). The overall activity of the dogs in the UC-II supplemented with glucosamine and chondroitin group (group IV) was significantly better than the glucosamine + chondroitin-supplemented group (group III). Glucosamine and chondroitin alleviated some pain, but in combination with UC-II (group IV) provided significant reductions in overall pain (57%), pain upon limb manipulation (53%), and exercise-associated lameness (53%). Following withdrawal of supplements, all dogs (groups II to IV) experienced a relapse of pain. None of the dogs in any groups showed any adverse effects or change in liver or kidney function markers or body weight. Data of this placebo-controlled study demonstrate that daily treatment of arthritic dogs with UC-II alone or in combination with glucosamine and chondroitin markedly alleviates arthritic-associated pain, and these supplements are well tolerated as no side effects were noted.

Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs.

DeParle L. A., Gupta R. C., Canerdy T. D., Goad J. T., D'Altilio M., Bagchi M., Bagchi D. Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs. J. vet. Pharmacol. Therap.28, 385-390. In large breed dogs, arthritis is very common because of obesity, injury, aging, immune disorder, or genetic predispositions. This study was therefore undertaken to evaluate clinical efficacy and safety of undenatured type-II collagen (UC-II) in obese-arthritic dogs. Fifteen dogs in three groups received either no UC-II (Group I) or UC-II with 1 mg/day (Group II) or 10 mg/day (Group III) for 90 days. Lameness and pain were measured on a weekly basis for 120 days (90 days treatment plus 30 days post-treatment). Blood samples were assayed for creatinine and blood urea nitrogen (markers of renal injury); and alanine aminotransferase and aspartate aminotransferase (evidence of hepatic injury). Dogs receiving 1 mg or 10 mg UC-II/day for 90 days showed significant declines in overall pain and pain during limb manipulation and lameness after physical exertion, with 10 mg showed greater improvement. At either dose of UC-II, no adverse effects were noted and no significant changes were noted in serum chemistry, suggesting that UC-II was well tolerated. In addition, dogs receiving UC-II for 90 days showed increased physical activity level. Following UC-II withdrawal for a period of 30 days, all dogs experienced a relapse of overall pain, exercise-associated lameness, and pain upon limb manipulation. These results suggest that daily treatment of arthritic dogs with UC-II ameliorates signs and symptoms of arthritis, and UC-II is well tolerated as no adverse effects were noted.