title: covR Mediated Antibiofilm Activity of 3-Furancarboxaldehyde Increases the Virulence of Group A Streptococcus.
abstract: BACKGROUND
  Group A streptococcus (GAS, Streptococcus pyogenes), a multi-virulent, exclusive human pathogen responsible for various invasive and non-invasive diseases possesses biofilm forming phenomenon as one of its pathogenic armaments. Recently, antibiofilm agents have gained prime importance, since inhibiting the biofilm formation is expected to reduce development of antibiotic resistance and increase their susceptibility to the host immune cells.
  
  
  RESULTS
  The current study demonstrates the antibiofilm activity of 3Furancarboxaldehyde (3FCA), a floral honey derived compound, against GAS biofilm, which was divulged using crystal violet assay, light microscopy, and confocal laser scanning microscopy. The report is extended to study its effect on various aspects of GAS (morphology, virulence, aggregation) at its minimal biofilm inhibitory concentration (132μg/ml). 3FCA was found to alter the growth pattern of GAS in solid and liquid medium and increased the rate of auto-aggregation. Electron microscopy unveiled the increase in extra polymeric substances around cell. Gene expression studies showed down-regulation of covR gene, which is speculated to be the prime target for the antibiofilm activity. Increased hyaluronic acid production and down regulation of srtB gene is attributed to the enhanced rate of auto-aggregation. The virulence genes (srv, mga, luxS and hasA) were also found to be over expressed, which was manifested with the increased susceptibility of the model organism Caenorhabditis elegans to 3FCA treated GAS. The toxicity of 3FCA was ruled out with no adverse effect on C. elegans.
  
  
  CONCLUSIONS
  Though 3FCA possess antibiofilm activity against GAS, it was also found to increase the virulence of GAS. This study demonstrates that, covR mediated antibiofilm activity may increase the virulence of GAS. This also emphasizes the importance to analyse the acclimatization response and virulence of the pathogen in the presence of antibiofilm compounds prior to their clinical trials.
authors.affiliation: Department of Biotechnology, Alagappa University, Science Campus, Karaikudi, Tamil Nadu, India.
authors.forename: Ganapathy
authors.initials: G
authors.lastname: Ashwinkumar Subramenium
authors.affiliation: Department of Biotechnology, Alagappa University, Science Campus, Karaikudi, Tamil Nadu, India.
authors.forename: Dharmaprakash
authors.initials: D
authors.lastname: Viszwapriya
authors.affiliation: Department of Biotechnology, Alagappa University, Science Campus, Karaikudi, Tamil Nadu, India.
authors.forename: Prasanth Mani
authors.initials: PM
authors.lastname: Iyer
authors.affiliation: Department of Biotechnology, Alagappa University, Science Campus, Karaikudi, Tamil Nadu, India.
authors.forename: Krishnaswamy
authors.initials: K
authors.lastname: Balamurugan
authors.affiliation: Department of Biotechnology, Alagappa University, Science Campus, Karaikudi, Tamil Nadu, India.
authors.forename: Shunmugiah
authors.initials: S
authors.lastname: Karutha Pandian
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D018441:Biofilms / Q000187:drug effects*; D017173:Caenorhabditis elegans / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000187:drug effects; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects / Q000235:genetics; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology; D012097:Repressor Proteins / Q000235:genetics*; D013290:Streptococcal Infections / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000187:drug effects* / Q000235:genetics*; D014774:Virulence / Q000187:drug effects* / Q000235:genetics*; D055549:Volatile Organic Compounds / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; C432143:CsrR protein, Streptococcus pyogenes; D010936:Plant Extracts; D012097:Repressor Proteins; D055549:Volatile Organic Compounds