New Evidence of Common Gastric Infection as Invasive Pathogen May Explain Antibiotic Resistance
Helicobacter pylori, the bacterium largely associated with gastritis and peptic ulcers in humans, may invade and replicate in gastric epithelial cells say researchers from China. This discovery disputes prior views of H. pylori as a noninvasive pathogen and could offer significant insight into its ability to resist antibacterial therapy and its biological life cycle as a whole. The details are reported in the October 2010 issue of the journal Infection and Immunity.
H. pylori infects more than 50% of the human population in developing countries, however, symptoms such as chronic active gastritis and peptic ulcers only manifest in 10 to 20% of those infected. Until now, H. pylori has been generally considered noninvasive, but current research indicates that it may replicate on the cell membrane ultimately forming a microcolony.
"This suggests that H. pylori can be considered a facultative intracellular organism," say the researchers.
In the study testing was conducted to determine if H. pylori could invade and multiply in gastric epithelial cells. Results showed a 5-fold increase in the number of bacteria cultured from infected cells 12 hours following infection when compared with the number of invading cells observed after 2 and a half hours. Additionally, the researchers note that only cell-penetrating antibiotics may effectively kill intracellular replicating H. pylori bacteria.
"The multiplication of H. pylori within cells provides a niche for its resistance to antibacterial therapy and has a significant impact on its biological life cycle," say the researchers.
(Y.T. Chu, Y.H. Wang, J.J. Wu, H.Y. Lei. 2010. Invasion and multiplication of Helicobacter pylori in gastric epithelial cells and implications for antibiotic resistance. Infection and Immunity; 78.10: 4157-4165.)
Newly Identified Virus May Cause Pediatric Diarrhea
Klassevirus, a new member of the picornavirus family, has recently been discovered in human stool and more specifically linked with pediatric diarrhea. Researchers from the U.S. and abroad detail their findings in the October 2010 issue of the journal Clinical and Vaccine Immunology.
Initial analysis of klassevirus shows it to be closely related to Aichi virus, a common cause of oyster-associated gastroenteritis in humans. Although studies have detected klassevirus in pediatric stool and sewage samples, it has not yet been found in any sterile sites of the human body leaving researchers to question its true authenticity as a human infection.
Prior studies of hepatitis A virus, a prototypic picornavirus, in chimps suggest that anti-3C antibodies only generate in actively infected individuals. Here, researchers developed a blood test for klassevirus infection incorporating recombinant klassevirus 3C protease (not present in picornavirus particles) to demonstrate human infection and determine prevalence in a sample pediatric group from hospitals in the St. Louis area. Results showed that anti-3C antibodies were detected up to 7 months following klassevirus infection indicating actual virus replication.
"The data in this study indicate that IgG antibodies are generated against the 3C protease after klassevirus infection," say the researchers. "This represents the first demonstration of a human antibody response to a klassevirus antigen and suggests that bona fide human infection by klassevirus occurs."
(A.L. Greninger, L. Holtz, G. Kang, D. Ganem, D. Wang, J.L. DeRisi. 2010. Serological evidence of human klassevirus infection. Clinical and Vaccine Immunology, 17. 10: 1584-1588.)
New Treatment May Protect Against Pneumonia
Intranasal administration of the protein flagellin may activate innate immunity and protect against acute pneumonia say researchers from France. They report their findings in the October 2010 issue of the journal Infection and Immunity.
Streptococcus pneumoniae is a major cause of respiratory infections in infants and the elderly worldwide. Many humans carry the bacterium in their throat, but remain asymptomatic due to activated innate immunity, however, inadequate immune responses in susceptible individuals can result in invasive pneumococcal pneumonia.
Researchers determined the capacity of flagellin to protect against pneumonia by intranasally inoculating two groups of mice with S. pneumoniae and simultaneously treating only one with flagellin. Mice treated with flagellin had a survival rate between 75 and 100% while untreated mice died within 3 to 4 days. Also, infected mice receiving flagellin treatment demonstrated significant bacterial reduction in the lungs after 24 hours and complete clearance after 2 days.
Additionally, researchers evaluated the therapeutic value of flagellin treatment by infecting two groups of mice with S. pneumoniae and then intranasally administering flagellin to only one after 24 hours. Protection levels among treated mice were 60 to 100 %, while all untreated mice died.
"Our results showed that local stimulation with a single and well-characterized molecule, specifically flagellin, is sufficient for augmenting lung innate immune defenses and controlling pneumococcal pneumonia, highlighting the benefits of using microbe-associated molecular patterns as the basis for developing antimicrobial therapies," say the researchers.
(N. Munoz, L. Maele, J.M. Marques, A. Rial, J.C. Sirard, J.A. Chabalgoity. 2010. Mucosal administration of flagellin protects mice from Streptococcus pneumoniae lung infection. Infection and Immunity, 78. 10: 4226-4233.)