Conditions Under Which Glutathione Disrupts the Biofilms and Improves Antibiotic Efficacy of Both ESKAPE and Non-ESKAPE Species

Abstract

Bacterial antibiotic resistance has increased in recent decades, raising concerns in hospital and community settings. Novel, innovative strategies are needed to eradicate bacteria, particularly within biofilms, and diminish the likelihood of recurrence. In this study, we investigated whether glutathione (GSH) can act as a biofilm disruptor, and enhance antibiotic effectiveness against various bacterial pathogens. Biological levels (10 mM) of GSH did not have a significant effect in inhibiting growth or disrupting the biofilm in four out of six species tested. However, exposure to 30 mM GSH showed >50% decrease in growth for all bacterial species, with almost 100% inhibition of Streptococcus pyogenes and an average of 94–52% inhibition for Escherichia coli , Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-sensitive S. aureus (MSSA) and multi-drug resistant Acinetobacter baumannii (MRAB) isolates, respectively. Klebsiella pneumoniae and Enterobacter sp. isolates were however, highly resistant to 30 mM GSH. With respect to biofilm viability, all species exhibited a >50% decrease in viability with 30 mM GSH, with confocal imaging showing considerable change in the biofilm architecture of MRAB isolates. The mechanism of GSH-mediated biofilm disruption is possibly due to a concentration-dependent increase in GSH acidity that triggers cleaving of the matrix components. Enzymatic treatment of MRAB revealed that eDNA and polysaccharides are essential for biofilm stability and eDNA removal enhanced amikacin efficiency. Combination of GSH, amikacin and DNase-I showed the greatest reduction in MRAB biofilm viability. Additionally, GSH alone and in combination with amikacin fostered human fibroblast cell (HFF-1) growth and confluence while inhibiting MRAB adhesion and colonization.

Role of tryptophan-metabolizing microbiota in mice diarrhea caused by Folium sennae extracts

“…We also found that diarrhea intervened by Folium sennae increased the expression of pathogenic bacteria such as Streptococcus and Mycoplasma in intestinal tract of mice. Streptococcus and Mycoplasma in biofilm growth phase are principally responsible for an array of infections within hospital and bacteria in the biofilm state could resist host immune response and triggers infection [24]. The mice were given oral intranasal Streptococcus pneumoniae and induced antigen-specific mucosal and systemic immune responses, which is closely related to the severity of diarrhea [25].…”

New roles for glutathione: Modulators of bacterial virulence and pathogenesis

“…On the other hand, exogenous GSH has been described in many studies to be capable of disrupting biofilms of various bacterial strains and improving antibiotic efficacy. The effects of GSH disruption of biofilms have been reported at high concentrations, ranging from 1 mM to 30 mM and for monomicrobial biofilms of P. aeruginosa , S. pyogenes , S. aureus , K. pneumoniae , Enterobacter sp., E. coli and A. baumannii , including clinical and multidrug resistant (MDR) strains [ [47] , [48] , [49] ]. Several studies also investigated the potential mode of action of exogenous GSH on biofilm disruption and the enhancement of antibiotic effectiveness, examining transcriptome changes [ 48 ] or the effect on MDR efflux pumps or beta-lactamase activity post-GSH treatment [ 49 ].…”

“…These findings, however, should be examined prudently as GSH at high concentrations is highly acidic (i.e. 20 mM of GSH has a pH of 3.92 and 3.89 when dissolved in Luria Broth (LB) or Phosphate buffered saline (PBS) respectively) [ 3 , 47 ]. A study reported that 30 mM GSH at neutral pH of 7.2 did not decrease the viability of MDR A. baumannii biofilm (76–94%) whereas 30 mM GSH at unbuffered intrinsic pH significantly decreased biofilm viability (16–38%) [ 47 ].…”

Role of Tryptophan-Metabolizing Microbiota On Diarrhea Mice Caused by Folium sennae Extracts

“…Streptococcus and Mycoplasma in biofilm growth phase are principally responsible for an array of infections within hospital and bacteria in the biofilm state could resist host immune response and triggers infection [29]. The mice were given oral intranasal Streptococcus pneumoniae and induced antigen-specific mucosal and systemic immune responses, which is closely related to the severity of diarrhea [30].…”