Specific Bacterial Species May Initiate, Maintain Crohn's

Patients newly diagnosed with pediatric Crohn's disease had significantly different levels of certain types of bacteria in their intestinal tracts than age-matched controls, according to a paper in the October Journal of Clinical Microbiology. The work may ultimately lead to treatment involving manipulation of the intestinal bacteria.

The research grew out of many years' study of gastrointestinal diseases, a particular focus being the role of mucus-associated bacteria in inflammatory conditions, says Hazel M. Mitchell of the University of New South Wales, Sydney, Australia, the principle investigator on the study.

"We deliberately chose to examine children newly diagnosed with Crohn's Disease, as we thought this would increase our chances of detecting species that may be involved in initiating Crohn's disease," she says, noting that confounding factors potentially affecting intestinal flora such as antibiotic or anti-inflammatory intake, smoking, or alcohol consumption, are less likely to be present in such children than in adults.

Of particular interest was the finding that one group of bacteria, known as Proteobacteria, was present at higher levels in mild cases, as compared with moderate to severe disease, and controls. That finding, "suggests that this group may play a role in initiation of the disease," says Mitchell, who credits her colleague Nadeem O. Kaakoush with much of the thought and laboratory work behind the study. "The latter finding is consistent with recent studies showing that members of the Proteobacteria, including E. coli and Campylobacter concisus may play a role in initiating Crohn's disease," says Mitchell.

There had been an indication that such was the case, prior to the current study, when the team's earlier research revealed C. concisus to be present in children who already had Crohn's, but not in healthy controls. That information in hand, the researchers grew C. concisus from biopsy specimens from Crohn's children and examined their ability to attach and invade intestinal cells, as compared with strains grown from patients with gastroenteritis, and healthy controls. That research showed that only specific C. concisus strains could invade intestinal cells, that these strains were associated with Crohn's, and that they carried a plasmid which was absent from noninvasive C. concisus strains.

But studies examining dysbiosis (out of balance microbial populations) in adults with Crohn's were inconsistent. That led Mitchell and her colleages to conduct the current study in children with newly diagnosed Crohn's. The results support the theory that Crohn's is linked to a gastrointestinal imbalance in the microbiota, says Mitchell. The bacteria associated with mild disease, including C. concisus, may be initiating infection, she says.

(N.O. Kaakoush, A.S. Day, K.D. Huinao, S.T. Leach, D.A. Lemberg, S.E. Dowd, and H.M. Mitchell, 2012. Microbial dysbiosis in pediatric patients with Crohn's Disease. J. Clin Microbiol. 50:3258-3266.)

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Antibodies to Immune Cells Protect Eyes In Pseudomonas Infection

Contact lenses, particularly the extended wear variety, render wearers vulnerable to eye infections from Pseudomonas aeruginosa. These infections can cause severe damage, including blindness. Treating the eye with antibodies to the inflammatory immune compound interleukin-17 (IL-17) reduced eye damage and the number of bacteria in a mouse model. The research is published in the October Infection and Immunology.

The onslaught of Pseudomonas infection of the eye is often swift, and is aggravated by the bacterium's resistance to antibiotics. "Pseudomonas is everywhere in the environment, and can be unwittingly introduced into the lens cleaning solution, or directly onto the contact lens, so everyone who uses contact lenses is at risk," says principal investigator Gregory P. Priebe of Brigham and Women's Hospital, Boston, and Boston Children's Hospital.

Immune cells known as neutrophils are a major cause of the eye damage that ensues from Pseudomonas infection. IL-17 is involved in attracting neutrophils to the infected tissues. They are the vanguard of immune attack, arriving at a site of infection within an hour, trapping, and ingesting pathogens. In their pathogen-killing function, they also release noxious substances, notably elastase, an enzyme that can chew up tissues, and superoxide, which is converted into hypochlorous acid, more commonly known as chlorine bleach. Thus, the ensuing eye damage is not surprising.

Nonetheless, the strategy of blocking these pathogen killing cells risked reducing the immune system's bacteria-killing function, says Priebe. "Surprisingly, just the opposite was seen: blocking IL-17 with antibodies led both to fewer neutrophils in the eye, and to fewer bacteria," says Priebe. Thus, he says, the research may lead to effective treatments.

"We thought that blocking IL-17 infection might worsen eye infections, but found just the opposite,' says Priebe . "Interestingly, this is a common pattern in eye infections. The body's responses that make the damage worse are often the same things needed to limit infections in other tissues, such as the lung."

(T.S. Zaidi, T. Zaidi, G.B. Pier, and G.P. Priebe, 2012. Topical neutralization of interleukin-17 during experimental Pseudomonas aeruginosa corneal infection promotes bacterial clearance and reduces pathology. Infect. Immun. 80:3706-3712.)

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Dangerous Form of MRSA, Endemic In Many US Hospitals, Increasing in UK

Prevalence of a particularly dangerous form of methicillin resistant Staphylococcus aureus (MRSA) jumped three-fold in just two years, in hospitals in the United Kingdom, according to a paper in the October 2012 Journal of Clinical Microbiology.

This particular pathogen emerged in the US in 1998, and "is endemic within many US hospitals," an observation which led to the current study being conducted, says coauthor Gopal Rao of Northwick Park Hospital, Harrow, Middlesex, UK.

The MRSA in question contains a toxin called Panton-Valentine leukocidin (PVL), which destroys leukocytes (a type of white blood cell), kills skin and mucus membranes, and confers increased virulence. In some cases, they cause invasive disease, most notably necrotizing hemorrhagic pneumonia, which has a high mortality rate.

The United Kingdom's Health Protection Agency first reported that PVL-methicillin resistant S. aureus (PVL-MRSA) was an emerging disease in UK in 2005. While most of the MRSA gets transmitted from one person to another within the hospital, most patients infected with MRSA containing the PVL toxin genes acquired it outside of the hospital ("community acquired" MRSA). The Department of Health in UK mandated screening for MRSA in 2008.

Rao and collaborators set out to find out how many patients entering the hospital carried community-acquired MRSA, especially that containing the dangerous PVL genes. During the study period, cases of community-acquired PVL-MRSA jumped threefold, from 0.07 percent to 0.22 percent, while the numbers of patients with hospital-acquired MRSA dropped from 4.6 percent to 2.8 percent. One particular clone of PVL-MRSA, which also carries resistance to clindamycin and tetracycline is particularly worrisome, the researchers note.

Most of the patients carrying PVL-containing strains are males. The study included 56,000 patients.

(N.M. Pantelides, G.G. Rao, A. Charlett, and A.M. Kearns, 2012. Preadmission screening of adults highlights previously unrecognized carriage of Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus in London: a cause for concern? J. Clin. Microbiol. 50:3168-3171.)

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