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Serum resistance and phase variation of a nasopharyngeal non-typeable Haemophilus influenzae isolate

Abstract : Haemophilus influenzae harbours a complex array of factors to resist human complement attack. As non-typeable H. influenzae (NTHi) strains do not possess a capsule, their serum resistance mainly depends on other mechanisms including LOS decoration. In this report, we describe the identification of a highly serum resistant, nasopharyngeal isolate (NTHi23) by screening a collection of 77 clinical isolates. For NTHi23, we defined the MLST sequence type 1133, which matches the profile of a previously published invasive NTHi isolate. A detailed genetic analysis revealed that NTHi23 shares several complement evading mechanisms with invasive disease isolates. These mechanisms include the functional expression of a retrograde phospholipid trafficking system and the presumable decoration of the LOS structure with sialic acid. By screening the NTHi23 population for spontaneous decreased serum resistance, we identified a clone, which was about 103-fold more sensitive to complement-mediated killing. Genome-wide analysis of this isolate revealed a phase variation in the N'-terminal region of lpsA, leading to a truncated version of the glycosyltransferase (LpsA). We further showed that a NTHi23 lpsA mutant exhibits a decreased invasion rate into human alveolar basal epithelial cells. Since only a small proportion of the NTHi23 population expressed the serum sensitive phenotype, resulting from lpsA phase-off, we conclude that the nasopharyngeal environment selected for a population expressing the intact and functional glycosyltransferase.
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Submitted on : Tuesday, January 12, 2021 - 7:11:33 PM
Last modification on : Friday, September 30, 2022 - 9:32:08 AM
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Sabine Lichtenegger, Isabelle Bina, Sanel Durakovic, Philippe Glaser, Sarah Tutz, et al.. Serum resistance and phase variation of a nasopharyngeal non-typeable Haemophilus influenzae isolate. International Journal of Medical Microbiology, 2017, 307 (2), pp.139-146. ⟨10.1016/j.ijmm.2017.01.005⟩. ⟨pasteur-03107776⟩



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