Haemophilus influenzae encompasses several strains of bacteria that are opportunistically pathogenic in humans, mostly in infants and young children. Nontypable Haemophilus influenzae (NTHi) is a predominant cause of infections in the middle ear, or otitis media, which often require treatment with antibiotics or the insertion of ear tubes. Like many bacterial pathogens, NTHi exhibits phase variation, a mechanism whereby different parts of the same bacterial population can express the same gene differentially. In some cases, phase variation can modulate genes that contribute to virulence, causing disease with one phenotype and causing no symptoms with another.

Recent work by Michael P. Jennings of Griffith University (Gold Coast, Australia) and colleagues has examined this characteristic in NTHi, analyzing pathogenic strains to understand how phase variation of a gene for DNA methyltransferase, termed modA, effects phenotypes that contribute to bacterial virulence (Nat. Commun. 6, 7828; 2015). Jennings' team created natural 'ON' and 'OFF' strains of NTHi, in which different alleles of modA were fully expressed or disrupted throughout populations of NTHi. They then put these strains through a series of tests to determine whether certain traits might be common or differentially expressed during phase variation. These tests showed that phase variation of modA alleles influences factors such as antibiotic susceptibility and immunoevasion.

Finally, the researchers examined NTHi in an in vivo model, inoculating chinchillas with either an 'ON' strain of NTHi or its corollary 'OFF' strain. Samples over the course of 22 days revealed that, on the one hand, chinchillas that received the predominantly 'ON' strain consistently yielded samples with the same 'ON' expression during infection of the middle ear. On the other hand, chinchillas that received the predominantly 'OFF' strain showed a transition during the course of the study, with later samples showing an 'ON' expression as well.

This transition demonstrates how phase variation, a natural ability to switch between phenotypes, can convey fitness advantages in an infecting population. However, the authors emphasize, by studying these phenotypes researchers might eventually define a stable immunological target for future treatments of NTHi. The authors even noted that phase variation of modA influences the expression of some proteins that are candidate targets for vaccine development.

“Through this research we have been able to understand the lifestyle of the bug and its adaptation to us as hosts,” Jennings summarized in a press release. “We now have a better idea of which surface proteins are good targets for vaccine development.”