Widespread use of Lactobacillus OppA, a surface located protein, as an adhesin that recognises epithelial cell surface glycosaminoglycans

Abstract

Specific adherence is the first requisite that a microorganism has to fulfil to become established onto a mucosal surface. It was previously shown that the OppA surface protein of Lactobacillus salivarius Lv72 bound HeLa cell cultures through interaction with glycosaminoglycans (GAGs). To determine whether this is a peculiarity of that strain or whether it can be extended to other lactobacilli, 12 strains, belonging to six species, were confronted with HeLa-cell cultures in the presence of soluble GAGs. Interference was observed to six of them, heparan sulphate and chondroitin sulphate C being more interfering than chondroitin sulphate A or chondroitin sulphate B. Furthermore, inhibition of the biosynthesis of GAGs or their elimination from the cell surface with specific enzymes also resulted in reduced adherence. Analysis of the surface proteome of Lactobacillus crispatus Lv25 and of Lactobacillus reuteri RC14 revealed single proteins that immunoreacted with antibodies raised against OppA, the main adhesin of L. salivarius Lv72. Upon MALDI-TOF-TOF analysis, they were identified as OppA-like proteins, thus indicating that these proteins participate as adhesins in attachment of diverse lactobacilli to the surface of human epithelial cells.

Adherence of Lactobacillus salivarius to HeLa Cells Promotes Changes in the Expression of the Genes Involved in Biosynthesis of Their Ligands

“…OppA modeling revealed the presence of a groove on its surface whose diameter matched the width of GAG-chains. The introduction of mutations on triplets encoding positively charged amino acids located on the vicinity of the groove blocked binding, thus confirming the role of OppA as a Lactobacilli adhesin, and that of GAGs, especially HS, as being its receptor on the mucosal surface (23)(24)(25)(26).…”

“…A variety of bacterial adhesins and eukaryotic receptors have been found to mediate the attachment of Lactobacilli to the mucosal surfaces. Among them, the mutual recognition between OppA and GAGs that are part of the epithelial glycocalix appears to play a significant role and several lines of evidence support this (23,25,26). The benefits linked to the mutualism derived from the interaction between Lactobacilli and the human mucosa suggest that both participants might have evolved mechanisms to strengthen their initial casual contact in order to stabilize their symbiotic relationship.…”

Urinary Glycosaminoglycans are Associated with Recurrent UTI and Urobiome Ecology in Postmenopausal Women

“…Association of Lactobacillus species Lactobacillus crispatus, Lactobacillus salivarius, Lactobacillus reuteri with HeLa cells has been reported to be GAG-dependent. 18, 21 Interestingly, depletion of the GAG layer in the bladder of a rabbit UTI model led to an increased attachment of UPEC and Klebsiella pneumoniae , suggesting that the GAG layer may impede uropathogen adherence to the urothelium. 13, 55, 56 Indeed, it is known that some uropathogens, such as Streptococcus agalactiae and Proteus mirabilis , can degrade CS.…”

“…16-20 Although species of the most predominant urobiome genus, Lactobacillus , cannot degrade CS, HS, or HA, Lactobacillus crispatus, Lactobacillus salivaris , and Lactobacillus reuteri have been shown to adhere to HeLa cells in a GAG-dependent manner. 15, 18, 21 These observations suggest that the urothelial GAG layer may serve as a scaffolding site for urobiome species.…”

Pharmacology of Heparin and Related Drugs: An Update

“…The use of cell surface GAGs as attachment factors for bacterial adhesins is commonplace among many species of bacteria, whether Gram 1ve or -ve, pathogenic, or harmless (Garc ıa et al, 2016;Zimmermann et al, 2016;Lin et al, 2017;Rajas et al, 2017;Mart ın et al, 2019;Shi et al, 2021). Panels of bacterial species have been screened for GAG-mediated adherence to both lung-derived (Rajas et al, 2017) and corneal-derived cells (Garc ıa et al, 2016), demonstrating the involvement of both CS and HS, particularly HS carried by the proteoglycan syndecan (Zimmermann et al, 2016).…”