Characterization of lactate utilization and its implication on the physiology of Haemophilus influenzae

Please always quote using this URN: urn:nbn:de:bvb:20-opus-121335
  • Haemophilus influenzae is a Gram-negative bacillus and a frequent commensal of the human nasopharynx. Earlier work demonstrated that in H. influenzae type b, l-lactate metabolism is associated with serum resistance and in vivo survival of the organism. To further gain insight into lactate utilization of the non-typeable (NTHi) isolate 2019 and laboratory prototype strain Rd KW20, deletion mutants of the l-lactate dehydrogenase (lctD) and permease (lctP) were generated and characterized. It is shown, that the apparent KM of l-lactate uptake isHaemophilus influenzae is a Gram-negative bacillus and a frequent commensal of the human nasopharynx. Earlier work demonstrated that in H. influenzae type b, l-lactate metabolism is associated with serum resistance and in vivo survival of the organism. To further gain insight into lactate utilization of the non-typeable (NTHi) isolate 2019 and laboratory prototype strain Rd KW20, deletion mutants of the l-lactate dehydrogenase (lctD) and permease (lctP) were generated and characterized. It is shown, that the apparent KM of l-lactate uptake is 20.1μM as determined for strain Rd KW20. Comparison of the COPD isolate NTHi 2019-R with the corresponding lctP knockout strain for survival in human serum revealed no lactate dependent serum resistance. In contrast, we observed a 4-fold attenuation of the mutant strain in a murine model of nasopharyngeal colonization. Characterization of lctP transcriptional control shows that the lactate utilization system in H. influenzae is not an inductor inducible system. Rather negative feedback regulation was observed in the presence of l-lactate and this is dependent on the ArcAB regulatory system. Additionally, for 2019 it was found that lactate may have signaling function leading to increased cell growth in late log phase under conditions where no l-lactate is metabolized. This effect seems to be ArcA independent and was not observed in strain Rd KW20. We conclude that l-lactate is an important carbon-source and may act as host specific signal substrate which fine tunes the globally acting ArcAB regulon and may additionally affect a yet unknown signaling system and thus may contribute to enhanced in vivo survival.show moreshow less

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Metadaten
Author: Sabine Lichtenegger, Isabelle Bina, Sandro Roier, Stilla Bauernfeind, Kristina Keidel, Stefan Schild, Mark Anthony, Joachim Reidl
URN:urn:nbn:de:bvb:20-opus-121335
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Hygiene und Mikrobiologie
Language:English
Parent Title (English):International Journal of Medical Microbiology
Year of Completion:2014
Volume:304
Issue:3-4
Pagenumber:490-8
Source:International Journal of Medical Microbiology 304 (2014) 490–498. http://dx.doi.org/10.1016/j.ijmm.2014.02.010
DOI:https://doi.org/10.1016/j.ijmm.2014.02.010
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/24674911
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:I-lactate; IctP; colonization; haemophilus influenzae; utilization
Release Date:2016/02/18
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung