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Imipenem Heteroresistance in Nontypeable Haemophilus influenzae

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Defense Thèse de doctorat : Univ. Genève, 2019 - Sc. 5375 - 2019/06/27
Abstract In the post-vaccine era, the nontypeable (i.e. nonencapsulated) Haemophilus influenzae (NTHi) revealed as an opportunistic pathogen causing and exacerbating multiple upper and lower respiratory tract diseases. Worryingly, several studies in various post-vaccine populations have observed a steadily increase of NTHi invasive incidence rates and antibiotic resistance. In this thesis work, we provide evidence indicating that altered penicillin-binding protein 3 (PBP3), slowed drug influx and direct efflux regulation contribute to the development of imipenem hetero-resistance in NTHi. We then established that the enhancement of imipenem-heteroresistant NTHi susceptibility to imipenem under heat stress conditions depends largely on the expression levels of PBP1b, AcrAB-TolC, and OmpP2, indicating again the role of the same pathways. Finally, we characterized the mechanisms of resistance to fluoroquinolones and macrolides in H. influenzae; assessed the extent of the AcrAB-TolC-mediated imipenem resistance; and defined a core genome multilocus sequence typing (cgMLST) scheme for H. influenzae by using whole-genome sequencing.
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URN: urn:nbn:ch:unige-1229907
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CHERKAOUI, Abdessalam. Imipenem Heteroresistance in Nontypeable Haemophilus influenzae. Université de Genève. Thèse, 2019. https://archive-ouverte.unige.ch/unige:122990

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Deposited on : 2019-09-11

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