Anti-infective potential of plant-derived quorum sensing inhibitors against multi-drug resistant human and aquatic bacterial pathogens.

The present study intended to decipher the anti-infective potential of bioactive phytocompounds, such as rosmarinic acid, morin, naringin, chlorogenic acid, and mangiferin, against aquatic and human bacterial pathogens using Artemia spp. nauplii and Caenorhabditis elegans as animal models, respectively. Initially, the test compounds were screened against the QS traits in Vibrio spp., such as bioluminescence production and biofilm formation. The test compounds effectively inhibited the bioluminescence in V. harveyi. Further, the confocal laser scanning microscopic analysis revealed that these natural compounds could efficiently reduce the clumping morphology, a characteristic biofilm formation in Vibrio spp., without inhibiting bacterial growth. The results of in vivo analysis showed a significant increase in the survival of Artemia spp. nauplii infected with Vibrio spp. upon exposure to these compounds. Moreover, the compounds used in this study were already proven and reported for their quorum sensing inhibitory efficacy against Pseudomonas aeruginosa. Hence, the anti-infective efficacy of these compounds against P. aeruginosa (PAO1) and its clinical isolates (AS1 and AS2) was studied using C. elegans as a live animal model system. The results of time-killing assay deciphered that rosmarinic acid and naringin are being the most effective ones in rescuing the animals from P. aeruginosa infection followed by morin, mangiferin, and chlorogenic acid. Further, the toxicity results revealed that these compounds did not show any lethal effect on C. elegans and Artemia spp. nauplii at the tested concentrations. In conclusion, the phytochemicals used in this study were effective in controlling the QS-regulated virulence traits in Vibrio spp. and P. aeruginosa infections in Artemia spp. nauplii and C. elegans animal model systems, respectively.

Fabrication of heteroatom doped NFP-MWCNT and NFB-MWCNT nanocomposite from imidazolium ionic liquid functionalized MWCNT for antibiofilm and wound healing in Wistar rats: Synthesis, characterization, in-vitro and in-vivo studies.

Bacterial biofilm is an obstacle for wound healing because it can affect the epithelialization, development of granular cells, and other regular inflammatory procedures. It plays the role of safeguarding pathogens from antiseptics and antibiotics. In this respect, this research work aims to develop heteroatom (N, F, P/B) incorporated multi-walled carbon nanotubes (MWCNT), such as NFP-MWCNT and NFB-MWCNT, which can maximize the wound healing efficacy via destroying the wound pathogen and biofilms. NFP-MWCNT and NFB-MWCNT were obtained using self-assembling ionic liquids (ILs) such as BMIM-PF6 and BMIM-BF4 in an acid-functionalized MWCNT (A-MWCNT) suspension, followed by pyrolysis in a nitrogen atmosphere. The composite formation was established by FTIR, XRD, RAMAN, EDX mapping, and XPS spectroscopy. TEM and SEM analyses confirmed the bamboo stick-like morphology. During this reaction, IL molecules might be cross-linked with A-MWCNT via hydrogen bonding and ionic interaction, with further pyrolysis producing the defects with doping of N, F, P, or B elements. Finally, they were assessed for their antibiofilm activity against typical bacterial strains such as K. pneumoniae, P. aeruginosa, E. coli (Gram-negative), and B. subtilis (Gram-positive), using a quantitative estimation approach. The results revealed greater effectiveness of NFB-MWCNT and NFP-MWCNT, compared to pristine MWCNT. The antibiofilm activity of NFP-MWCNT and NFB-MWCNT was associated with their specific surface chemistry (due to the presence of N, F, P/B heteroatoms), and their nanosize. Moreover, the synthesized material was examined for its wound-healing ability in Wistar rats. The results proved that cells cultured on NFB-MWCNT and NFP-MWCNT displayed exceptional healing ability. The different electronegativity between the heteroatoms creates the surface charge that inhibits the biofilm formation, leading to healing the wounds together with the heteroatom mineral source for mouse fibroblast regeneration and granulation. This is the first study in which the role of different heteroatoms incorporated into MWCNT is examined in the context of antibiofilm-associated wound-healing ability.

In vivo protective effect of geraniol on colonization of Staphylococcus epidermidis in rat jugular vein catheter model.

Staphylococcal infections associated with indwelling medical devices are difficult to eradicate owing to its recalcitrant nature of biofilms to conventional antibiotics. In our earlier study, we reported the efficacy of geraniol (GE) in inhibiting the in vitro biofilm formation of Staphylococcus epidermidis and adaptive resistant development. To examine the in vivo potential of GE in eradicating the in vivo colonization of S. epidermidis, an implanted rat jugular vein catheter model was developed. Oral supplementation of GE (GE at 200 mg/kg bw for three days) in rats infected with S. epidermidis exhibited a significant reduction of the bacterial burden in catheter, blood, heart and kidney, when compared to the untreated infection control. In addition, GE supplemented animals showed significantly reduced level of inflammatory markers such as nitric oxide and malondialdehyde in heart and kidney tissues. Furthermore, in contrast to the infection control, histopathology analysis of the heart and kidney tissues of the GE-treated group showed a normal histoarchitecture similar to animal control. Thus, the outcome of the present study exhibits the potential of GE as antibiofilm and anti-inflammatory agent against S. epidermidis infections. Furthermore, elucidating the molecular mechanism of GE is important to exploit the therapeutic efficacy of GE.

Inhibition of quorum sensing-dependent biofilm and virulence genes expression in environmental pathogen Serratia marcescens by petroselinic acid.

The aim of this study was to evaluate the anti-biofilm and anti-virulence properties of petroselinic acid (PSA) against the environmental pathogen Serratia marcescens. PSA significantly inhibited the quorum sensing (QS)-dependent virulence factors such as prodigiosin, protease productions, and biofilm formation in S. marcescens. The antibiofilm potential of PSA was also confirmed through light, confocal laser scanning, and scanning electron microscopic analyses. Furthermore, PSA effectively inhibited the biofilm-related phenomena such as exopolysaccharide production, hydrophobicity production, swimming, and swarming motility without affecting the bacterial growth. In FT-IR analysis, the PSA treated S. marcescens cells displayed a reduction in cellular components compared to the untreated controls. The real-time analysis revealed the downregulation of QS-controlled virulence genes such as bsmB, fimA, fimC, and flhD in S. marcescens on treatment with PSA. The obtained results strongly suggested that PSA could be further explored as an antipathogenic drug to treat QS-mediated infections caused by S. marcescens.

Antiquorum sensing and antibiofilm potential of Capparis spinosa.

BACKGROUND: Emergence of antibiotic resistance among bacterial pathogens often leads to the failure of existing antibiotics to treat bacterial infections; thus, there is a need to seek alternative treatment measures. The aim of this study was to evaluate the anti-quorum sensing (anti-QS) and antibiofilm potential of Capparis spinosa to prevent the onset of bacterial infections as an alternate to antibiotics. METHODS: The methanolic extract of the dried fruits of C. spinosa was assessed for its activity in inhibiting QS-depedent phenomenon such as violacein pigment production in Chromobacterium violaceum, biosurfactant production in Pseudomonas aeruginosa PAO1, swimming and swarming motility, exopolysaccharide production (EPS) and biofilm formation in Escherichia coli, Proteus mirabilis, Serratia marcescens and PAO1. RESULTS: Extract of C. spinosa showed a higher degree of anti-QS activity in a dose dependent manner without affecting the bacterial growth. At 2 mg/mL, this extract significantly (p ≤0.005) inhibited the biofilm formation to 79, 75, 73, 70% and EPS production to 58, 46, 66 and 67% in S. marcescens, PAO1, E. coli and P. mirabilis, respectively. It also exhibited inhibition in swimming and swarming motility of bacterial pathogens. The non-enzymatic nature of the anti-QS compound in C. spinosa was confirmed by proteinase K and heat treatment. CONCLUSIONS: Because the methanolic extract of C. spinosa demonstrated anti-QS and antibiofilm activity at 0.5-2 mg/mL, it could be further exploited for novel molecules to treat the emerging infections of antibiotic resistant bacterial pathogens.