Abstract
The two-component regulatory system PhoP/PhoQ has been shown to (i) control expression of virulence-associated traits, (ii) confer survival and growth within macrophages and (iii) play a role in Yersinia infections. However, the influence of PhoP on virulence varied greatly between different murine models of infection and its role in natural oral infections with frequently used representative isolates of Y. pseudotuberculosis was unknown. To address this issue, we constructed an isogenic set of phoP + and phoP − variants of strain IP32953 and YPIII and analyzed the impact of PhoP using in vitro functionality experiments and a murine oral infection model, whereby we tested for bacterial dissemination and influence on the host immune response. Our results revealed that PhoP has a low impact on virulence, lymphatic and systemic organ colonization, and on immune response modulation by IP32953 and YPIII, indicating that PhoP is not absolutely essential for oral infections but may be involved in fine-tuning the outcome. Our work further revealed certain strain-specific differences in virulence properties, which do not strongly rely on the function of PhoP, but affect tissue colonization, dissemination and/or persistence of the bacteria. Highlighted intra-species variations may provide a potential means to rapidly adjust to environmental changes inside and outside of the host.
Highlights
The lifestyle of most enteric bacterial pathogens, those frequently circulating between external reservoirs and warmblooded hosts, demand efficient strategies to survey and respond to their permanently varying environments
Previous work demonstrated that the PhoP/PhoQ two-component regulatory systems (TCSs) affects replication of Y. pseudotuberculosis in macrophages, but its role in virulence, in particular upon the natural oral infection route is not clear
It has been reported that PhoP/PhoQ is required for virulence in Y. pseudotuberculosis 32777 by the intragastric route [6], strain YPIII is still able to cause lethal disease in the oral murine mouse infection model [40]
Summary
The lifestyle of most enteric bacterial pathogens, those frequently circulating between external reservoirs and warmblooded hosts, demand efficient strategies to survey and respond to their permanently varying environments. The most rapid and efficient strategy of adjusting gene transcription involves the highly conserved two-component regulatory systems (TCSs) These TCSs typically comprise a membrane-spanning sensor kinase, which monitors extracellular components (e.g. certain nutrients or ions) and transduces the signal to a DNAbinding cognate response regulator via a histidine to aspartate phosphorelay [1,2,3]. Based on genome-wide in silico analysis it was predicted that the entero-pathogenic bacterium Yersinia pseudotuberculosis encodes 24 different TCSs [4,5] Several of these systems were found to promote tolerance towards certain environmental stresses (e.g. inorganic/organic acids/low pH, high salinity, low iron/magnesium, antimicrobial peptides such as polymyxin B, and hydrogen peroxide) and were shown to be important for virulence [4,6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
