Group A Streptococcus (GAS) is a human specific pathogen capable of causing both mild infections and severe invasive disease. We and others have shown that GAS is able to form biofilms during infection. That is to say, they form a three-dimensional, surface attached structure consisting of bacteria and a multi-component extracellular matrix. The mechanisms involved in regulation and dispersal of these GAS structures are still unclear. Recently we have reported that in the absence of the transcriptional regulator Srv in the MGAS5005 background, the cysteine protease SpeB is constitutively produced, leading to increased tissue damage and decreased biofilm formation during a subcutaneous infection in a mouse model. This was interesting because MGAS5005 has a naturally occurring mutation that inactivates the sensor kinase domain of the two component regulatory system CovRS. Others have previously shown that strains lacking covS are associated with decreased SpeB production due to CovR repression of speB expression. Thus, our results suggest the inactivation of srv can bypass CovR repression and lead to constitutive SpeB production. We hypothesized that Srv control of SpeB production may be a mechanism to regulate biofilm dispersal and provide a mechanism by which mild infection can transition to severe disease through biofilm dispersal. The question remained however, is this mechanism conserved among GAS strains or restricted to the unique genetic makeup of MGAS5005. Here we show that Srv mediated control of SpeB and biofilm dispersal is conserved in the invasive clinical isolates RGAS053 (serotype M1) and MGAS315 (serotype M3), both of which have covS intact. This work provides additional evidence that Srv regulated control of SpeB may mediate biofilm formation and dispersal in diverse strain backgrounds.

The results of this study support the premise that carbon nanotubes may be effectively utilised as highly localised photothermal agents with the potential for translation into the clinical treatment of bacterial infections of soft tissue.

Nanotubes (NT) composed of the electrically active polymer poly (3,4-ethylenedioxythiophene) (PEDOT) have been used for photothermal ablation of both gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria. Since infrared absorption of PEDOT is dominated by bipolarons strongly coupled to phonons, we hypothesize that nonradiative decay of these states leads to heat generation. Photothermal death of bacteria by PEDOT NT was compared to single-wall carbon nanotubes (SWNT). Complete eradication of bacterial colonies incubated with 100 ug/ml of either PEDOT NT or SWNT occurred with a single exposure to 1064 nm light (3.8 W/cm2) for 60 s. PEDOT NT were also shown to elicit a mild antibacterial response upon incubation with bacteria and no infrared exposure. PEDOT NT have the same capacity for photothermal ablation of bacteria as compared to SWNT; therefore, they represent an exciting new class of polymer based nanoparticles for medically-relevant photothermal therapies.