Impact of Lactobacillus plantarum Sortase on Target Protein Sorting, Gastrointestinal Persistence, and Host Immune Response Modulation

Remus, Daniela M.; Bongers, Roger S.; Meijerink, Marjolein; Poolman, Bert; Vos, Paul de; Wells, Jerry M.; Kleerebezem, Michiel; Bron, Peter A.

doi:10.1128/jb.01321-12

Cited by 39 publications

(39 citation statements)

References 60 publications

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“…In this work, the role of sortase was examined in relation to desirable probiotic phenotypes, such as survival in simulated GIT juices, adherence to mucin and IECs, immunomodulatory capacity and persistence and colonization in a murine model. For both L. acidophilus and L. gasseri, sortase deficiency did not alter survival in simulated GIT juices, which is consistent with previous observations in L. plantarum WCFS1 (Remus et al, 2013). In addition, the ability to adhere to Caco-2 IECs was not affected by the DsrtA mutations.…”

Section: Discussionsupporting

confidence: 80%

“…Previous work with a sortase-deficient strain of L. plantarum WCFS1 found no effect on gut retention; however, this was determined using only two mice and in a conventional murine model (Remus et al, 2013). Persistence of the sortase-deficient strain of L. acidophilus NCK2232 was evaluated in a germ-free mouse model.…”

Section: Discussionmentioning

confidence: 99%

“…Both mutants contain in-frame deletions of approximately 90 % of the sortase gene. Due to the deficiency of SrtA, these strains are also expected to lack the surface display of predicted SDPs (Dieye et al, 2010;Remus et al, 2013). When both DsrtA mutants were examined for their growth characteristics in culture medium (MRS) and survival in SGJ and SIJ, neither L. acidophilus NCK2232 nor L. gasseri NCK2256 showed growth impairment or increased LGAS_1725 1993 2 *The presence of a signal peptide was determined using InterProScan (http://www.ebi.ac.uk/Tools/pfa/iprscan/).…”

Section: Construction Of Sortase-deficient Mutantsmentioning

confidence: 99%

“…Similarly, SDPs play a role in the virulence of several other Gram-positive pathogenic species such as Listeria monocytogenes (Bierne et al, 2002) and Streptococcus pneumoniae (Paterson & Mitchell, 2006). Meanwhile, the role of SrtA has only recently been studied in species of commensal and probiotic microbes, including Lactobacillus casei BL23 (Muñoz-Provencio et al, 2012), Lactococcus lactis IL1403 (Dieye et al, 2010), Lactobacillus plantarum WCFS1 (Remus et al, 2013) and Lactobacillus salivarius UCC118 (O'Callaghan et al, 2012;van Pijkeren et al, 2006). These studies demonstrated that SrtA and SDPs play pivotal roles in the adhesion to intestinal epithelial cells (IECs), immune modulation of DCs, as well as the expression of mucin genes in Caco-2 IECs.…”

Section: Introductionmentioning

confidence: 99%

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Sortase-deficient lactobacilli: effect on immunomodulation and gut retention

et al. 2015

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Surface proteins of probiotic microbes, including Lactobacillus acidophilus and Lactobacillus gasseri, are believed to promote retention in the gut and mediate host-bacterial communications. Sortase, an enzyme that covalently couples a subset of extracellular proteins containing an LPXTG motif to the cell surface, is of particular interest in characterizing bacterial adherence and communication with the mucosal immune system. A sortase gene, srtA, was identified in L. acidophilus NCFM (LBA1244) and L. gasseri ATCC 33323 (LGAS_0825). Additionally, eight and six intact sortase-dependent proteins were predicted in L. acidophilus and L. gasseri, respectively. Due to the role of sortase in coupling these proteins to the cell wall, DsrtA deletion mutants of L. acidophilus and L. gasseri were created using the upp-based counterselective gene replacement system. Inactivation of sortase did not cause significant alteration in growth or survival in simulated gastrointestinal juices. Meanwhile, both DsrtA mutants showed decreased adhesion to porcine mucin in vitro. Murine dendritic cells exposed to the DsrtA mutant of L. acidophilus or L. gasseri induced lower levels of pro-inflammatory cytokines TNF-a and IL-12, respectively, compared with the parent strains. In vivo co-colonization of the L. acidophilus DsrtA mutant and its parent strain in germ-free 129S6/SvEv mice resulted in a significant one-log reduction of the DsrtA mutant population. Additionally, a similar reduction of the DsrtA mutant was observed in the caecum. This study shows for the first time that sortase-dependent proteins contribute to gut retention of probiotic microbes in the gastrointestinal tract.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Construction Of Sortase-deficient Mutantsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sortase-deficient lactobacilli: effect on immunomodulation and gut retention

et al. 2015

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“…Sortase-dependent cell wall proteins play a crucial role in interactions of Gram-positive bacteria with their environment (38). The vaginal mucosa is colonized by beneficial bacteria, often with lactobacilli dominating the niche (39).…”

Section: Discussionmentioning

confidence: 99%

The Highly Autoaggregative and Adhesive Phenotype of the Vaginal Lactobacillus plantarum Strain CMPG5300 Is Sortase Dependent

Malik

Petrova

Claes

et al. 2013

Appl Environ Microbiol

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h Lactobacilli are important for the maintenance of a healthy ecosystem in the human vagina. Various mechanisms are postulated but so far are poorly substantiated by molecular studies, such as mutant analysis. Bacterial autoaggregation is an interesting phenomenon that can promote adhesion to host cells and displacement of pathogens. In this study, we report on the identification of a human vaginal isolate, Lactobacillus plantarum strain CMPG5300, which shows high autoaggregative and adhesive capacity. To investigate the importance of sortase-dependent proteins (SDPs) in these phenotypes, a gene deletion mutant was constructed for srtA, the gene encoding the housekeeping sortase that covalently anchors these SDPs to the cell surface. This mutant lost the capacity to autoaggregate, showed a decrease in adhesion to vaginal epithelial cells, and lost biofilm-forming capacity under the conditions tested. These results indicate that the housekeeping sortase SrtA of CMPG5300 is a key determinant of the peculiar surface properties of this vaginal Lactobacillus strain.

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Genotypic adaptations associated with prolonged persistence of Lactobacillus plantarum in the murine digestive tract

Veen

Smelt

Wels

et al. 2013

Biotechnology Journal

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Probiotic bacteria harbor effector molecules that confer health benefits, but also adaptation factors that enable them to persist in the gastrointestinal tract of the consumer. To study these adaptation factors, an antibiotic-resistant derivative of the probiotic model organism Lactobacillus plantarum WCFS1 was repeatedly exposed to the mouse digestive tract by three consecutive rounds of (re)feeding of the longest persisting colonies. This exposure to the murine intestine allowed the isolation of intestine-adapted derivatives of the original strain that displayed prolonged digestive tract residence time. Re-sequencing of the genomes of these adapted derivatives revealed single nucleotide polymorphisms as well as a single nucleotide insertion in comparison with the genome of the original WCFS1 strain. Detailed in silico analysis of the identified genomic modifications pinpointed that alterations in the coding regions of genes encoding cell envelope associated functions and energy metabolism appeared to be beneficial for the gastrointestinal tract survival of L. plantarum WCFS1. This work demonstrates the feasibility of experimental evolution for the enhancement of the gastrointestinal residence time of probiotic strains, while full-genome resequencing of the adapted isolates provided clues towards the bacterial functions involved. Enhanced gastrointestinal residence is industrially relevant because it enhances the efficacy of the delivery of viable probiotics in situ.

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Impact of Lactobacillus plantarum Sortase on Target Protein Sorting, Gastrointestinal Persistence, and Host Immune Response Modulation

Cited by 39 publications

References 60 publications

Sortase-deficient lactobacilli: effect on immunomodulation and gut retention

Sortase-deficient lactobacilli: effect on immunomodulation and gut retention

The Highly Autoaggregative and Adhesive Phenotype of the Vaginal Lactobacillus plantarum Strain CMPG5300 Is Sortase Dependent

Genotypic adaptations associated with prolonged persistence of Lactobacillus plantarum in the murine digestive tract

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