Bacterial fight-and-flight responses enhance virulence in a polymicrobial infection.
The oral pathogen Aggregatibacter actinomycetemcomitans (Aa) resides in infection sites with many microbes, including commensal streptococci such as Streptococcus gordonii (Sg). During infection, Sg promotes the virulence of Aa by producing its preferred carbon source, l-lactate, a phenomenon referred to as cross-feeding. However, as with many streptococci, Sg also produces high levels of the antimicrobial hydrogen peroxide (H2O2), leading to the question of how Aa deals with this potent antimicrobial during coinfection. Here, we show that Aa possesses two complementary responses to H2O2: a detoxification or fight response mediated by catalase (KatA) and a dispersion or flight response mediated by Dispersin B (DspB), an enzyme that dissolves Aa biofilms. Using a murine abscess infection model, we show that both of these responses are required for Sg to promote Aa virulence. Although the role of KatA is to detoxify H2O2 during coinfection, 3D spatial analysis of mixed infections revealed that DspB is required for Aa to spatially organize itself at an optimal distance (>4 µm) from Sg, which we propose allows cross-feeding but reduces exposure to inhibitory levels of H2O2. In addition, these behaviors benefit not only Aa but also Sg, suggesting that fight and flight stimulate the fitness of the community. These results reveal that an antimicrobial produced by a human commensal bacterium enhances the virulence of a pathogenic bacterium by modulating its spatial location in the infection site.
Department of Molecular Biosciences, Institute of Cellular and Molecular Biology, Center for Infectious Disease, The University of Texas at Austin, Austin, TX 78712; and.
Apollo
A
Stacy
Department of Surgery, Texas Tech University Health Sciences Center, Lubbock, TX 79430.
Jake
J
Everett
Department of Molecular Biosciences, Institute of Cellular and Molecular Biology, Center for Infectious Disease, The University of Texas at Austin, Austin, TX 78712; and.
Peter
P
Jorth
Department of Surgery, Texas Tech University Health Sciences Center, Lubbock, TX 79430.
Urvish
U
Trivedi
Department of Surgery, Texas Tech University Health Sciences Center, Lubbock, TX 79430.
Kendra P
KP
Rumbaugh
Department of Molecular Biosciences, Institute of Cellular and Molecular Biology, Center for Infectious Disease, The University of Texas at Austin, Austin, TX 78712; and mwhiteley@austin.utexas.edu.
Marvin
M
Whiteley
D016976:Aggregatibacter actinomycetemcomitans / Q000378:metabolism / Q000472:pathogenicity*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development*; D002374:Catalase / Q000378:metabolism*; D060085:Coinfection / Q000382:microbiology / Q000503:physiopathology*; D006026:Glycoside Hydrolases / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D051379:Mice; D046228:Microarray Analysis; D054773:Streptococcus gordonii / Q000378:metabolism*; D014774:Virulence
D001426:Bacterial Proteins; D019344:Lactic Acid; D006861:Hydrogen Peroxide; D002374:Catalase; D006026:Glycoside Hydrolases; C501330:dispersin B, Actinobacillus actinomycetemcomitans
microbial ecology; microbiota; microenvironment; multispecies; synergy