A Moonlighting Enolase from Lactobacillus gasseri does not Require Enzymatic Activity to Inhibit Neisseria gonorrhoeae Adherence to Epithelial Cells

Spurbeck, Rachel R.; Harris, Paul T.; Raghunathan, K.; Arvidson, Dennis N.; Arvidson, Cindy Grove

doi:10.1007/s12602-015-9192-8

Cited by 13 publications

(13 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bioactivity of several molecules that we identified in HIV-1-inhibiting EVs was reported earlier: several enolases derived from Lactobacillus were shown to inhibit the adherence of Neisseria gonorrhoeae to epithelial cells 34 . Moreover, bifidobacterial enolase, a cell-surface receptor for human plasminogen, was involved in interaction with human host cells 35 .…”

Section: Discussionsupporting

confidence: 65%

Extracellular vesicles from symbiotic vaginal lactobacilli inhibit HIV-1 infection of human tissues

et al. 2019

View full text Add to dashboard Cite

The vaginal microbiota, dominated by Lactobacillus spp., plays a key role in preventing HIV-1 transmission. Here, we investigate whether the anti-HIV effect of lactobacilli is mediated by extracellular vesicles (EVs) released by these bacteria. Human cervico-vaginal and tonsillar tissues ex vivo, and cell lines were infected with HIV-1 and treated with EVs released by lactobacilli isolated from vaginas of healthy women. EVs released by L. crispatus BC3 and L. gasseri BC12 protect tissues ex vivo and isolated cells from HIV-1 infection. This protection is associated with a decrease of viral attachment to target cells and viral entry due to diminished exposure of Env that mediates virus-cell interactions. Inhibition of HIV-1 infection is associated with the presence in EVs of several proteins and metabolites. Our findings demonstrate that the protective effect of Lactobacillus against HIV-1 is, in part, mediated by EVs released by these symbiotic bacteria. If confirmed in vivo, this finding may lead to new strategies to prevent male-to-female sexual HIV-1 transmission.

show abstract

Section: Discussionsupporting

confidence: 65%

Extracellular vesicles from symbiotic vaginal lactobacilli inhibit HIV-1 infection of human tissues

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In the fungal pathogen Aspergillus fumigatus , enolase also acts as a virulence factor in recruiting human regulators ( 53 ), and in Trichomonas vaginalis , enolase plays a role in virulence by activating plasminogen to plasmin ( 54 ). Interestingly, some commensal bacteria, including L. johnsonii, L. crispatus and L. plantarum , also encode enolases that can bind plasminogen and activate plasmin ( 55 ), among other moonlighting activities. A surface-associated protein homologous to enolase (Eno3) from L. gasseri ATC 3323 was found to inhibit the adherence of Neisseria gonorrhoeae to epithelial cells ( 55 ).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, some commensal bacteria, including L. johnsonii, L. crispatus and L. plantarum , also encode enolases that can bind plasminogen and activate plasmin ( 55 ), among other moonlighting activities. A surface-associated protein homologous to enolase (Eno3) from L. gasseri ATC 3323 was found to inhibit the adherence of Neisseria gonorrhoeae to epithelial cells ( 55 ). Similar to L. gasseri ATCC 33323, L. johnsonii N6.2 also has three enolase genes, and our results support the surface localization of Eno3 in L. johnsonii N6.2.…”

Section: Discussionmentioning

confidence: 99%

Identification of Biomarkers for Systemic Distribution of Nanovesicles From Lactobacillus johnsonii N6.2

et al. 2021

View full text Add to dashboard Cite

The ability of bacterial extracellular vesicles (EV) to transport biological molecules has increased the research to determine their potential as therapeutic agents. In this study, Lactobacillus johnsonii N6.2-derived nanovesicles (NV) were characterized to identify components that may serve as biomarkers in host-microbe interactions. Comparative proteomic and lipidomic analyses of L. johnsonii N6.2 NV and cell membrane (CM) were performed. The lipidomic profiles indicated that both fractions contained similar lipids, however, significant differences were observed in several classes. LC-MS/MS proteomic analysis indicated that NV contained several unique and differentially expressed proteins when compared to the CM. Analysis of Gene Ontology (GO) terms, based on cellular component, showed significant enrichment of proteins in the cytoplasm/intracellular space category for the NV fraction. Based on these results, the proteins T285_RS00825 (named Sdp), Eno3 and LexA were selected for studies of localization and as potential biomarkers for host-microbe interactions. Immunogold staining, followed by scanning and transmission electron microscopy (SEM and TEM, respectively), revealed that Sdp was preferentially localized along the cell wall/membrane, and on NV-like structures surrounding the bacteria. These results were confirmed using immunofluorescence staining in Caco-2 cells incubated with NV. Consequently, we evaluated the potential for NV surface-exposed proteins to generate an immune response in the host. Plasma from individuals administered L. johnsonii N6.2 showed that IgA and IgG antibodies were generated against NV and Sdp domains in vivo. Altogether, these results show that L. johnsonii N6.2 NV have the potential to mediate host interactions through immune modulation.

show abstract

“…To expand our consideration of species-specific differences and explore a potential environment in which DTZ would be clinically useful (the lower female reproductive tract), we tested the efficacy of DTZ against a representative vaginal commensal, Lactobacillus gasseri. L. gasseri has been previously shown to block N. gonorrhoeae-epithelial cell interactions (28,29), and lactobacilli in general maintain a low pH in the vagina that is an important determinant of discouraging Neisseria growth (30). We found that L. gasseri is greatly reduced in sensitivity to DTZ compared to that of N. gonorrhoeae as well as the previously described E. coli and Salmonella enterica (17).…”

mentioning

confidence: 49%

Selective Inhibition of Neisseria gonorrhoeae by a Dithiazoline in Mixed Infections with Lactobacillus gasseri

Lenz

Shirk

Jolicoeur

et al. 2018

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The Gram-negative human pathogenNeisseria gonorrhoeaehas progressively developed resistance to antibiotic monotherapies, and recent failures of dual-drug therapy have heightened concerns that strains resistant to all available antibiotics will begin circulating globally. Targeting bacterial cell wall assembly has historically been effective at treating infections withN. gonorrhoeae, but as the effectiveness of β-lactams (including cephalosporins) is challenged by increasing resistance, research has expanded into compounds that target the numerous other enzymes with roles in peptidoglycan metabolism. One example is the dithiazoline compound JNJ-853346 (DTZ), which inhibits the activity of anEscherichia coliserine proteasel,d-carboxypeptidase (LdcA). Recently, the characterization of an LdcA homolog inN. gonorrhoeaerevealed localization and activity differences from the characterizedE. coliLdcA, prompting us to explore the effectiveness of DTZ againstN. gonorrhoeae. We found that DTZ is effective at inhibitingN. gonorrhoeaein all growth phases, unlike the specific stationary-phase inhibition seen inE. coli. Surprisingly, DTZ does not inhibit gonococcal LdcA enzyme activity, and DTZ sensitivity is not significantly decreased inldcAmutants. While effective against numerousN. gonorrhoeaestrains, including recent multidrug-resistant isolates, DTZ is much less effective at inhibiting growth of the commensal speciesLactobacillus gasseri. DTZ treatment during coinfections of epithelial cells resulted in significant lowering of gonococcal burden and interleukin-8 secretion without significantly impacting recovery of viableL. gasseri. This selective toxicity presents a possible pathway for the use of DTZ as an effective antigonococcal agent at concentrations that do not impact vaginal commensals.

show abstract

A Moonlighting Enolase from Lactobacillus gasseri does not Require Enzymatic Activity to Inhibit Neisseria gonorrhoeae Adherence to Epithelial Cells

Cited by 13 publications

References 58 publications

Extracellular vesicles from symbiotic vaginal lactobacilli inhibit HIV-1 infection of human tissues

Extracellular vesicles from symbiotic vaginal lactobacilli inhibit HIV-1 infection of human tissues

Identification of Biomarkers for Systemic Distribution of Nanovesicles From Lactobacillus johnsonii N6.2

Selective Inhibition of Neisseria gonorrhoeae by a Dithiazoline in Mixed Infections with Lactobacillus gasseri

Contact Info

Product

Resources

About