Alginate oligosaccharides enhance diffusion and activity of colistin in a mucin-rich environment

Abstract

In a number of chronic respiratory diseases e.g. cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), the production of viscous mucin reduces pulmonary function and represents an effective barrier to diffusion of inhaled therapies e.g. antibiotics. Here, a 2-compartment Transwell model was developed to study impaired diffusion of the antibiotic colistin across an artificial sputum (AS) matrix/medium and to quantify its antimicrobial activity against Pseudomonas aeruginosa NH57388A biofilms (alone and in combination with mucolytic therapy). High-performance liquid chromatography coupled with fluorescence detection (HPLC-FLD) revealed that the presence of AS medium significantly reduced the rate of colistin diffusion (> 85% at 48 h; p < 0.05). Addition of alginate oligosaccharide (OligoG CF-5/20) significantly improved colistin diffusion by 3.7 times through mucin-rich AS medium (at 48 h; p < 0.05). Increased diffusion of colistin with OligoG CF-5/20 was shown (using confocal laser scanning microscopy and COMSTAT image analysis) to be associated with significantly increased bacterial killing (p < 0.05). These data support the use of this model to study drug and small molecule delivery across clinically-relevant diffusion barriers. The findings indicate the significant loss of colistin and reduced effectiveness that occurs with mucin binding, and support the use of mucolytics to improve antimicrobial efficacy and lower antibiotic exposure.

The effect of supernatant of Lactobacillus plantarum against Salmonella Typhi biofilm formation

“…Three highly biofilm-forming isolates were selected, which were named S.t1, S.t.3, and S.t.2 and the statistical analysis showed significant differences. Clear with a significant level of significance (P > 0.05) between the inhibitory effects of the studied components of both types of lactobacilli on the isolates of S. Typhi as in Figure (1)(2)(3)(4)(5). respectively, while the lowest inhibition zone was with a diameter of 15 mm for the two isolates S.t.2 and S.t.3 caused by the effect of suspended bacteria L.plantarum as in Table (1)(2)(3)(4)(5), and as a result of the results shown, the L. plantarum CFS was approved in subsequent experiments to inhibit and kill S. Typhi and prevent it from forming a biofilm.…”

“…Clear with a significant level of significance (P > 0.05) between the inhibitory effects of the studied components of both types of lactobacilli on the isolates of S. Typhi as in Figure (1)(2)(3)(4)(5). respectively, while the lowest inhibition zone was with a diameter of 15 mm for the two isolates S.t.2 and S.t.3 caused by the effect of suspended bacteria L.plantarum as in Table (1)(2)(3)(4)(5), and as a result of the results shown, the L. plantarum CFS was approved in subsequent experiments to inhibit and kill S. Typhi and prevent it from forming a biofilm. The results showed that L. plantarum has a clear inhibitory effect towards S.Typhi, but there is a discrepancy in this effect according to the type of isolate, as the diameters of the highest inhibition were for the CFS, which includes many inhibitory and lethal substances for pathogens, due to its production of secondary metabolic products such as microbial antibiotics,such as bacteriocins (11).…”

“…Biofilm forms in response to a number of factors such as high cellular density and unfavorable environmental conditions such as nutrient deficiencies or during antibiotic treatment (5), and biofilm-forming bacteria are responsible for chronic and incurable infections because they contribute to increased pathogenesis and (6) proved in his study that the biofilm has a protective role similar to the capsule in S. Typhi bacteria that is not surrounded by the capsule in giving it the ability to cause infection, as well as it has a key role as a shield for bacteria to stay for a longer period in the body, such as colonizing S. Typhi bacteria in chronic and asymptomatic gallbladder, This allows it to be transmitted to uninfected individuals (7), so treatment alternatives such as a probiotic are resorted to, which is characterized by its inhibitory effect on biofilm production and has no side effects in addition to its presence inside the body has multiple benefits (8).…”

“…Figure (1-7): Inhibition of the biofilm formed by S. Typhi bacteria with CFS produced by L.plantarum bacteria Figure (1-7) showed that L. plantarum CFS had the ability to remove the biofilm formed by S. Typhi bacteria on the inner surface of the micro titration plate, which is the most accurate and best method in detecting the formation or inhibition of the biofilm and bacteria adhesion(56), the results in Table(1)(2)(3)(4)(5)(6) showed that CFS CFS produced by L. plantarum had the ability to inhibit biofilm formation by 20 S. Typhi isolates in comparison with the positive control reading (S. Typhi cultured on TSB media). Without the CFS, the highest inhibition was 98.0% towards isolate S.T.6 and the lowest was 96.2% towards isolate S.T.15.…”

Innovative Strategies to Overcome Antimicrobial Resistance and Tolerance

“…It remains to be shown whether the recent pharmacological restoration of functionality of the cystic fibrosis transmembrane conductance regulator CFTR, that leads to diminished growth of pathogens and re-establishment of a conventional microflora, can be mimicked by altering the composition of the artificial sputum medium. Artificial medium use reflecting distinctly similar host conditions can also be applied to specifically monitor bacterial colonization in primary ciliary dyskinesia and chronic obstructive pulmonary diseases (COPD) [ 73 , 74 ].…”