Biology subjects

Solomon, A. P.

Publications and source records attributed to Solomon, A. P..

3 recordsLinked to original sources

bioRxiv2021

Controlling Staphylococcus aureus by 2-phenol (2-MAMP) in a co-culture moderates the biofilm and virulence of Pseudomonas aeruginosa

Staphylococcus aureus and Pseudomonas aeruginosa are the most encountered organisms in a polymicrobial chronic wound infection. Production of multiple virulence factors by this duo delays wound healing process. Notably, P. aeruginosa displays enhanced virulence in the presence of S. aureus by a peptidoglycan sensing mechanism. Thus, novel therapies are imperative to address polymicrobial infections effectively. Previously, it has been suggested that targeting S. aureus might be a possible approach to reduce the severity of P. aeruginosa in a polymicrobial infection. In this aspect, we have used 2-[(Methylamino)methyl]phenol (2-MAMP), our previously reported QS inhibitor to target S. aureus and phenotypically determine the virulence factors of P. aeruginosa under this condition. Analysis of major virulence factors of Pseudomonas viz. biofilm, pyocyanin and pyoveridine showed a significant reduction. The competitive index (CI) and relative increase ratio (RIR) were determined to understand the organisms interaction in co-culture. Results indicated competitiveness among the strains and on increasing ratios of S. aureus cells, co-existence was noticed. Further, as a sensible approach antibiotic - antivirulence drug combinations were tested on co-culture. Significant improvement in the growth inhibition was observed. Our preliminary results presented here would enable further research to address polymicrobial infection in a novel way.

microbiology↗

bioRxiv2021

Design of a novel DNA Gyrase B inhibitor with a rhodanine scaffold: in silico and in vitro approaches

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin intermediate-resistant Staphylococcus aureus (VRSA) is one among the WHO high priority pathogens. Among these two, MRSA is the most globally documented pathogen that necessitates the pressing demand for new classes of anti-MRSA drugs. Bacterial gyrase targeted therapeutics are unique strategies to overcome cross-resistance as they are present only in bacteria and absent in higher eukaryotes. The GyrB subunit is essential for the catalytic functions of the bacterial enzyme DNA Gyrase, thereby constituting a promising druggable target. The current study performed a structure-based virtual screening to designing GyrB target-specific candidate molecules. The de novo ligand design of novel hit molecules was performed using a rhodanine scaffold. Through a systematic in silico screening process, the hit molecules were screened for their synthetic accessibility, drug likeliness and pharmacokinetics properties in addition to its target specific interactions. Of the total 374 hit molecules obtained through de novo ligand design, qsl-304 emerged as the most promising ligand. qsl-304 was synthesized through a one-step chemical synthesis procedure, and the in vitro activity was proven, with an IC50 of 31.23 g/mL against the novobiocin resistant clinical isolate of Staphylococcus aureus sa-P2003. Further studies on time-kill kinetics showed the bacteriostatic nature with the diminished recurrence of resistance.

microbiology↗

bioRxiv2020

Curcumin-Sophorolipid nano-conjugate inhibits Candida albicans filamentation and biofilm development

Candida albicans is an opportunistic fungal pathogen that is highly resistant to contemporary antifungals, and a major reason for this appears to be their predominant, filamentation-mediated, biofilm lifestyle. Hence, agents that inhibit biofilms and filamentation of the yeast offer promise as next-generation antifungals. Curcumin is a natural polyphenol with several beneficial pharmacological attributes, yet limitations such as poor solubility, acid, and enzyme tolerance have impeded its practical utility. Sophorolipids are biologically-derived surfactants that serve as efficient carriers and delivery agents of hydrophobic molecules, such as curcumin, into biofilms. The aim of this study was to investigate the effects of a novel, curcumin-sophorolipid (CU-ASL) nano-conjugate on Candida albicans biofilms and filamentation. The effects of CU and ASL, in combination, and alone, were investigated on planktonic cells of the yeast. The effects of sub-inhibitory concentrations of the compounds were investigated on biofilm biomass and biofilm architecture. Their effects on filamentation was compared by scanning electron microscopic imaging, and gene expression analysis by qRT-PCR. Our results demonstrated that sub-inhibitory concentration of CU-ASL (9.37 {micro}g/mL) significantly inhibited candidal adhesion to substrates, and subsequent biofilm development, maturation, and filamentation. This effect was associated with significant downregulation of a select group of biofilm, adhesins, and hyphal regulatory genes. In conclusion, the curcumin-sophorolipid nano-conjugate is a potent inhibitor of the two major virulence attributes of C. albicans, biofilm formation and filamentation, thus highlighting its promise as a putative anti-candidal agent with low toxicity and biofilm penetrative potential.

microbiology↗