Mucin CYS domain stiffens the mucus gel hindering bacteria and spermatozoa

Abstract

Mucus is the first biological barrier encountered by particles and pathogenic bacteria at the surface of secretory epithelia. The viscoelasticity of mucus is governed in part by low energy interactions that are difficult to assess. The CYS domain is a good candidate to support low energy interactions between GFMs and/or mucus constituents. Our aim was to stiffen the mucus from HT29-MTX cell cocultures and the colon of mice through the delivery of a recombinant protein made of hydrophobic CYS domains and found in multiple copies in polymeric mucins. The ability of the delivery of a poly-CYS molecule to stiffen mucus gels was assessed by probing cellular motility and particle diffusion. We demonstrated that poly-CYS enrichment decreases mucus permeability and hinders displacement of pathogenic flagellated bacteria and spermatozoa. Particle tracking microrheology showed a decrease of mucus diffusivity. The empirical obstruction scaling model evidenced a decrease of mesh size for mouse mucus enriched with poly-CYS molecules. Our data bring evidence that enrichment with a protein made of CYS domains stiffens the mucin network to provide a more impermeable and protective mucus barrier than mucus without such enrichment.

The postcoital test in the development of new vaginal contraceptives†

“…This would be helpful in the context of progestin-only contraceptive methods that thicken cervical mucus but do not consistently prevent ovulation. For products that make it more difficult for sperm to penetrate mucus, these markers, including particle tracking, could be useful preclinically to predict effectiveness of the method [ 47 , 48 ]. In vitro testing could precede clinical studies by use of collected cervical secretions and sperm with particle tracking analysis to aid in product development.…”

Microfluidic Device Using Mouse Small Intestinal Tissue for the Observation of Fluidic Behavior in the Lumen

“…For future work, we will perfuse mucus-like liquid [29,30] or isotonic saline suspending living GB to understand the roles of the flow field in forming GB distribution in the SI tissue using this microfluidic device, and we will apply an inconstant flow as a simulation of peristatic motion. Furthermore, although the SI tissue used in our study was fixed and lost its biological activities, the superficial molecules on mucosal tissues and the shape of villi were properly maintained.…”

Impact and consequences of intensive chemotherapy on intestinal barrier and microbiota in acute myeloid leukemia: the role of mucosal strengthening

“…28 Although baseline colonization was similar in Wt and Tg mice, our results show that mucus reinforcement could limit microbiota diversity impairment and pathological bacterial translocation after induction chemotherapy. 29 For decades, improving the intestinal barrier has remained a challenge in patients undergoing chemotherapy. Various products have been evaluated to maintain intestinal homeostasis during the allo-SCT procedure, such as keratinocyte growth factor or analog of R-Spondin that inhibits heat shock proteins.…”

“… 28 Although baseline colonization was similar in Wt and Tg mice, our results show that mucus reinforcement could limit microbiota diversity impairment and pathological bacterial translocation after induction chemotherapy. 29 …”

“…There was a significant weight loss (expressed in percent of the weight at T0) at T1 (−2.6% [−5.7; 0.9]; p = .027) and T2 (−5.2% [−7.9; −0.5]; p = .006). Compared with T0 (29 [22][23][24][25][26][27][28][29][30][31][32][33] µmol/ L), citrulline levels decreased significantly at T1 (14 [10][11][12][13][14][15][16][17][18][19] µmo/L; p = .0002), and reached near normal values at T2 (25 [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] µmol/L; p = .412) ( Figure 1a). Over 70% of the patients (11/15) were in remission after induction chemotherapy (Figure 1a).…”