Adaptation of bacterial virulence to oxidative and nitrosative stress
Description: Reactive oxygen and nitrogen species stand as an evolutionary conserved cornerstone in host innate defence against microbial intruders. Pathogens often encounter oxidative and nitrosative stress during an infection. Radicals, as well as proteins and nucleic acids chemically modified by radical stress, could thereby pose as major environmental cues directing virulence gene expression and pathogen adaptation to the host immune system. Many strains of Salmonella enterica act as facultative intracellular pathogens capable of surviving and replicating in professional phagocytic cells. Concomitantly S. enterica and many of its virulence factors cope with oxidative and nitrosative stress. Thereby a first aim of this project plan is to use S. enterica as a probe to illuminate how bacterial virulence and core genome functions are mechanistically integrated in relation to oxidative and nitrosative stress. A second aim is to define to what extent host or de facto pathogen derived radical stress adds to bacterial bacterial virulence gene regulation, and hence to infection pathogenesis. Any detailing of such interactions will define novel molecular pathways for bacterial virulence in a more general term, to eventually provide new treatment and prevention strategies for infectious diseases.
Funder: Vetenskapsrådet
Amount: SEK 1,800,000
Funding type: research
Funder scheme: Project grant
Start date: 2012-01-01
End date: 2014-12-31
Investigator: Mikael Rhen
Institution: Karolinska Institutet
Funded outputs count: 2
Funder award ID: 2011-03379
OpenAlex ID: G1925215054