Jennewein, Jonas and Matuszak, Jasmin and Walter, Steffi and Felmy, Boas and Gendera, Kathrin and Schatz, Valentin and Nowottny, Monika and Liebsch, Gregor and Hensel, Michael and Hardt, Wolf-Dietrich and Gerlach, Roman G. and Jantsch, Jonathan (2015) Low-oxygen tensions found in Salmonella-infected gut tissue boost Salmonella replication in macrophages by impairing antimicrobial activity and augmenting Salmonella virulence. CELLULAR MICROBIOLOGY, 17 (12). pp. 1833-1847. ISSN 1462-5814, 1462-5822
Full text not available from this repository. (Request a copy)Abstract
In Salmonella infection, the Salmonella pathogenicity island-2 (SPI-2)-encoded type three secretion system (T3SS2) is of key importance for systemic disease and survival in host cells. For instance, in the streptomycin-pretreated mouse model SPI-2-dependent Salmonella replication in lamina propria CD11c(-)CXCR1(-) monocytic phagocytes/macrophages (M phi) is required for the development of colitis. In addition, containment of intracellular Salmonella in the gut critically depends on the antimicrobial effects of the phagocyte NADPH oxidase (PHOX), and possibly type 2 nitric oxide synthase (NOS2). For both antimicrobial enzyme complexes, oxygen is an essential substrate. However, the amount of available oxygen upon enteroinvasive Salmonella infection in the gut tissue and its impact on Salmonella-M phi interactions was unknown. Therefore, we measured the gut tissue oxygen levels in a model of Salmonella enterocolitis using luminescence two-dimensional in vivo oxygen imaging. We found that gut tissue oxygen levels dropped from approximate to 78 Torr (approximate to 11% O-2) to values of approximate to 16 Torr (approximate to 2% O-2) during infection. Because in vivo virulence of Salmonella depends on the Salmonella survival in M phi, Salmonella-M phi interaction was analysed under such low oxygen values. These experiments revealed an increased intracellular replication and survival of wild-type and t3ss2 non-expressing Salmonella. These findings were paralleled by blunted nitric oxide and reactive oxygen species (ROS) production and reduced SalmonellaROS perception. In addition, hypoxia enhanced SPI-2 transcription and translocation of SPI-2-encoded virulence protein. Neither pharmacological blockade of PHOX and NOS2 nor impairment of T3SS2 virulence function alone mimicked the effect of hypoxia on Salmonella replication under normoxic conditions. However, if t3ss2 non-expressing Salmonella were used, hypoxia did not further enhance Salmonella recovery in a PHOX and NOS2-deficient situation. Hence, these data suggest that hypoxia-induced impairment of antimicrobial activity and Salmonella virulence cooperate to allow for enhanced Salmonella replication in M phi.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | III SECRETION SYSTEM; ENTERICA SEROVAR TYPHIMURIUM; NITRIC-OXIDE SYNTHASE; ZN-SUPEROXIDE DISMUTASES; NADPH PHAGOCYTE OXIDASE; PATHOGENICITY ISLAND 2; IN-VIVO; GASTROINTESTINAL-TRACT; BACTERICIDAL ACTIVITY; MURINE SALMONELLOSIS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 May 2019 08:03 |
| Last Modified: | 07 May 2019 08:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4398 |
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