Host-inherent variability influences the transcriptional response of Staphylococcus aureus during in vivo infection.
The rise of antibiotic resistance calls for alternative strategies to treat bacterial infections. One attractive strategy is to directly target bacterial virulence factors with anti-virulence drugs. The expression of virulence traits by pathogens is, however, not constitutive but rather induced by the level of stress encountered within the host. Here we use dual RNA sequencing (RNA-seq) to show that intrinsic variability in the level of host resistance greatly affects the pathogen's transcriptome in vivo. Through analysis of the transcriptional profiles of host and pathogen during Staphylococcus aureus infection of two mouse strains, shown to be susceptible (A/J) or resistant (C57BL/6) to the pathogen, we demonstrate that the expression of virulence factors is dependent on the encountered host resistance. We furthermore provide evidence that this dependence strongly influences the efficacy of anti-virulence strategies, highlighting a potential limitation for the implementation of these strategies.
Infection Immunology Research Group, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
Robert
R
Thänert
Infection Immunology Research Group, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
Oliver
O
Goldmann
Institute for Pathology, University of Veterinary Medicine Hannover, Bünteweg 17, 30559 Hannover, Germany.
Andreas
A
Beineke
Infection Immunology Research Group, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
Eva
E
Medina
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D054884:Host-Pathogen Interactions; D051379:Mice; D008810:Mice, Inbred C57BL; D012329:RNA, Bacterial / Q000235:genetics; D017423:Sequence Analysis, RNA; D013045:Species Specificity; D013203:Staphylococcal Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity*; D014158:Transcription, Genetic; D059467:Transcriptome; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism
D000900:Anti-Bacterial Agents; D012329:RNA, Bacterial; D037521:Virulence Factors