Helicobacter pylori Accumulates Photoactive Porphyrins and Is Killed by Visible Light

Abstract

Helicobacter pylori colonizes the mucus layer of the human stomach and duodenum, causes chronic gastritis, gastric ulcer, and is a risk factor for gastric adenocarcinoma. There is a 20% failure rate in antibiotic therapy, which is increasingly due to antibiotic resistance and necessitates the search for alternative antimicrobial methods. We have discovered that H. pylori when cultured in liquid medium, accumulates significant quantities of coproporphyrin and protoporphyrin IX, both in the cells and secreted into the medium. These photoactive porphyrins lead to cell death (up to 5 logs) by photodynamic action upon illumination with low doses of visible light, with blue/violet light being most efficient. The degree of killing increases with the age of the culture and is greater than that found with Propionibacterium acnes (another bacterium known to be photosensitive due to porphyrin accumulation). Both virulent and drug-resistant strains are killed. The data suggest that phototherapy might be used to treat H. pylori infection in the human stomach.Helicobacter pylori is a gram-negative microaerophilic bacterium which selectively colonizes the mucus layer of the human stomach and duodenum (7). As more than 50% of the world population is infected and in some countries infection rates approach 90%, H. pylori can be termed the world's commonest infectious agent (19). H. pylori infection has been shown to be strongly associated with the presence of inflammation and chronic gastritis, and once acquired, H. pylori persists, usually for life, unless eradicated by antimicrobial therapy (15). It is now known that H. pylori is a major cause of peptic ulcer disease, and in 1994, the International Agency for Cancer Research declared that H. pylori was a carcinogen of humans and was implicated in the development of gastric cancer (11).The most common antibacterial treatment regimens include bismuth, metronidazole, tetracycline, and a proton pump inhibitor, or clarithromycin in combination with a proton pump inhibitor and amoxicillin (10). Combinations such as the above lead to eradication rates of about 80% but at the expense of side effects and possible poor patient compliance. Increasing development of antibiotic resistance among H. pylori isolates and the existence of nonresponsive patients suggest that alternative strategies for H. pylori eradication be sought (22).Photodynamic therapy uses the combination of nontoxic dyes (frequently porphyrins or their derivatives) and harmless visible light to produce cytotoxicity via generation of reactive oxygen species (25). Photodynamic therapy has been clinically approved for various malignant, premalignant, and ophthalmologic conditions (6). It has long been known that many microorganisms including gram-negative and gram-positive bacteria, mycoplasma, fungi, and viruses can be killed by photodynamic therapy, and recently photodynamic therapy has been investigated as a treatment for infectious disease (12). The grampositive bacterium that causes acne, Propionibacterium acnes, is kil...

Photodynamic antimicrobial therapy

“…and Prevotela sp., in which porphyrins are accumulated, and thus they are photosensitive depending on the outer environment and its conditions. The ability to accumulate porphyrins has been demonstrated in Propionibacterium acnes and Helicobacter pylori [27]. Our knowledge of naturally produced photoactive porphyrins is still only fragmented and an explanation of the causes of this phenomenon is still unknown.…”

Helicobacter pylori moves through mucus by reducing mucin viscoelasticity

“…The narrow depth of focus made possible by the use of two-photon f luorescence excitation from a high speed laser scanning source facilitated imaging bacteria without washout from out-of-plane BCECF f luorescence. The use of two-photon excitation also allowed for extended duration live cell imaging of H. pylori as illumination of the specimen was accomplished with near infrared light, avoiding photodestruction because of blue light activation of porphyrins known to accumulate in this microorganism (42). In Fig.…”

All you need is light

“…146 This is actually also true in H. pylori infected patients, whom the application of 405 nm endoscopic light alone was capable of reducing Colony Forming Unit (CFU) counts by about 90%. 147 PDT's very nature makes it ideal for the treatment of skin, wound and burn infections, all of which are easily accessible for light therapies.…”