TY - JOUR
T1 - Bacterial fight-and-flight responses enhance virulence in a polymicrobial infection
AU - Stacy, Apollo
AU - Everett, Jake
AU - Jorth, Peter
AU - Trivedi, Urvish
AU - Rumbaugh, Kendra P
AU - Whiteley, Marvin
PY - 2014/5/27
Y1 - 2014/5/27
N2 - 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.
AB - 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.
KW - Aggregatibacter actinomycetemcomitans/metabolism
KW - Animals
KW - Bacterial Proteins/metabolism
KW - Biofilms/growth & development
KW - Catalase/metabolism
KW - Coinfection/microbiology
KW - Glycoside Hydrolases/metabolism
KW - Hydrogen Peroxide/metabolism
KW - Lactic Acid/metabolism
KW - Mice
KW - Microarray Analysis
KW - Streptococcus gordonii/metabolism
KW - Virulence
U2 - 10.1073/pnas.1400586111
DO - 10.1073/pnas.1400586111
M3 - Journal article
C2 - 24825893
SN - 0027-8424
VL - 111
SP - 7819
EP - 7824
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 21
ER -