Abstract

BackgroundGroup 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.Principal FindingsThe 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.SignificanceThough 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.

Highlights

  • Streptococcus pyogenes, called group A streptococcus (GAS) is a β-haemolytic pathogen which exclusively affects human and naturally inhabits human skin and throat [1,2]

  • Since no significant increase in the activity was observed at higher concentrations, 132 μg/ml was considered as Minimum Biofilm Inhibitory Concentration (MBIC) (Fig 1)

  • Biofilm formation is considered as one of the most important virulent factors of microorganism which help them to survive in hostile conditions and prevents penetration of antibiotics to the cells encased in it [30]

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Summary

Introduction

Streptococcus pyogenes, called group A streptococcus (GAS) is a β-haemolytic pathogen which exclusively affects human and naturally inhabits human skin and throat [1,2]. It ranks among top ten infectious pathogens, affecting 700 million individuals and causing mortality over 500,000 per year globally [3]. It is an originator of wide number of invasive and non-invasive diseases like pharyngitis (strep throat), necrotizing fasciitis and streptococcal toxic shock syndrome [4]. 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. 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

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