Analysis of invasive non-typeable Haemophilus influenzae isolates reveals a selection for the expression state of particular phase-variable lipooligosaccharide biosynthetic genes

ABSTRACT

Non-typeable Haemophilus influenzae (NTHi) is a major human pathogen, responsible for several acute and chronic infections of the respiratory tract. The incidence of invasive infections caused by NTHi is increasing world-wide. NTHi is able to colonise the nasopharynx asymptomatically, and the exact change(s) responsible for transition from benign carriage to overt disease are not understood. We have previously reported that phase-variation (the rapid and reversible ON-OFF switching of gene expression) of particular lipooligosaccharide (LOS) glycosyltransferases occurs during transition from colonising the nasopharynx to invading the middle ear. Variation in the structure of the LOS is dependent on the ON/OFF expression status of each of the glycosyltransferases responsible for LOS biosynthesis. In this study we surveyed a collection of invasive NTHi isolates for ON/OFF expression status of seven phase-variable LOS glycosyltransferases. We report that the expression state of the LOS biosynthetic genes oafA ON and lic2A OFF show a correlation with invasive NTHi isolates. We hypothesise that these gene expression changes contribute to the invasive potential of NTHi. OafA expression, which is responsible for the addition of an O-acetyl group onto the LOS, has been shown to impart a phenotype of increased serum resistance, and may serve as a marker for invasive NTHi.