A bacteriophage hitchhiker may turn a harmless bacterium into a meningitis-causing menace, according to Bille and colleagues on page 1905. Neisseria meningitidis—a frequent resident of the human upper respiratory tract—may become a killer if it contains this phage integrated into its chromosome.

An eight-kilobase genetic island encodes an integrated bacteriophage that is associated with disease in hyperinvasive strains of N. meningitidis.

N. meningitidis is usually a commensal bacterium that lives in the upper respiratory tract, most often without incident. However, certain “hyperinvasive” strains of N. meningitidis can occasionally invade the blood stream and cross the blood–brain barrier, triggering outbreaks of life-threatening meningitis. Several bacterial factors are required for bacterial virulence, including the polysaccharides that form the bacterial capsule and the type IV pilus adhesin protein. But these structures are widely distributed among meningococcal strains, including those that do not cause illness, suggesting that other factors are also important in causing disease.

In search of elements that might confer pathogenicity, Bille et al. analyzed 29 hyperinvasive and 20 noninvasive N. meningitidis isolates using a gene array. This revealed an eight kilobase genetic island present in 100% of hyperinvasive isolates and absent from 90% of noninvasive isolates. This island looked and acted like an integrated bacteriophage, existing independently as a double-stranded form in the cytoplasm and being released into the bacterial supernatant as a nuclease-resistant (presumably encapsidated) single-stranded circular form.

The association of the phage-like element with disease was confirmed when the authors analyzed isolates from a previous epidemiologic study and found that those containing the phage were more likely to have caused disease. How the phage renders N. meningitidis pathogenic remains a matter of speculation. One possibility, suggest the authors, is that the phage favors bacterial invasion into bloodstream, either by altering bacterial gene expression or manipulating the host immune system.