MicroCorrespondence:Phenotypic switching of Haemophilus influenzae

Type: COMMENT Type: LETTER Language: EngNRC publication: Ye

The length of a tetranucleotide repeat tract in Haemophilus influenzae determines the phase variation rate of a gene with homology to type III DNA methyltransferases.

Haemophilus influenzae is an obligate commensal of the upper respiratory tract of humans that uses simple repeats (microsatellites) to alter gene expression. The mod gene of H. influenzae strain Rd has homology to DNA methyltransferases of type III restriction/modification systems and has 40 tetranucleotide (5'-AGTC) repeats within its open reading frame. This gene was found in 21 out of 23 genetically distinct H. influenzae strains, and in 13 of these strains the locus contained repeats. H. influenzae strains were constructed in which a lacZ reporter was fused to a chromosomal copy of mod downstream of the repeats. Phase variation occurred at a high frequency in strains with the wild-type number of repeats. Mutation rates were derived for similarly engineered strains, containing different numbers of repeats. Rates increased linearly with tract length over the range 17-38 repeat units. The majority of tract alterations were insertions or deletions of one repeat unit with a 2:1 bias towards contractions of the tract. These results demonstrate the number of repeats to be an important determinant of phase variation rate in H. influenzae for a gene containing a microsatellite

Three genes, IgtF, lic2C and lpsA, have a primary role in determining the pattern of oligosaccharide extension from the inner core of Haemophilus influenzae LPS

NRC publication: Ye

Last glacial dynamics of the Vale of York and North Sea lobes of the British and Irish Ice Sheet

During the Last Glacial Maximum, the Vale of York and North Sea lobes of the British and Irish Ice Sheet extended to within 10 km of each other, impounding a series of pro-glacial lakes. Such an interplay of ice lobes provides a useful analogue for elsewhere in the North Sea basin. This paper focusses on reconstructing the Vale of York and North Sea Ice lobes using a regional suite of 25 luminescence ages in combination with stratigraphical and geomorphic evidence. Results extend and revise the chronology of the Dimlington LGM typesite, showing that the North Sea Ice lobe advanced between 20.9–17.1 ka and 17.1–15.1 ka before present. Initially this lobe impounded a proto Lake Humber which likely covered parts of Holderness as well as the southern part of the Vale of York. Later stages of Lake Humber within the Vale of York show continued blockage of the Humber Gap by the North Sea Ice lobe. The Vale of York Ice extended briefly at ∼18.7 ± 0.63 ka across Lake Humber into South Yorkshire and North Lincolnshire before retreating to and forming the Escrick and York moraines. Both glacier lobes appear to have been short-lived, comprising relatively dynamic ice, especially when moving into areas of deformable lacustrine sediments, which allowed them to rapidly advance and over-extend their margins due to low basal shear stress. Topographic control of the extent and spatial positioning of both Ice lobes also appears to have been significant

Genome sequencing of disease and carriage isolates of nontypeable Haemophilus influenzae identifies discrete population structure

One of the main hurdles for the development of an effective and broadly protective vaccine against non-encapsulated isolates of Haemophilus influenzae (NTHi) lies in the genetic diversity of the species, which renders extremely difficult the identification of cross-protective candidate antigens. To assess whether a population structure of NTHi could be defined, we performed genome sequencing of a collection of diverse clinical isolates representative of both carriage and disease and of the diversity of the natural population. Analysis of the distribution of polymorphic sites in the core genome and of the composition of the accessory genome defined distinct evolutionary clades and supported a predominantly clonal evolution of NTHi, with the majority of genetic information transmitted vertically within lineages. A correlation between the population structure and the presence of selected surface-associated proteins and lipooligosaccharide structure, known to contribute to virulence, was found. This high-resolution, genome-based population structure of NTHi provides the foundation to obtain a better understanding of NTHi adaptation to the host, as well as its commensal and virulence behavior, that could facilitate intervention strategies against disease caused by this important human pathoge