Lipoproteins in Gram-Positive Bacteria: Abundance, Function, Fitness

Nguyen, Minh-Thu; Matsuo, Miki; Niemann, Silke; Herrmann, Mathias; Götz, Friedrich

doi:10.3389/fmicb.2020.582582

Cited by 50 publications

(36 citation statements)

References 125 publications

(138 reference statements)

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“…To exert their function, after export from the cytoplasm, surface proteins must be retained on the cell wall. In G + bacteria, there are three known mechanisms that link surface proteins to the cell wall (for review, see references 35 to 37 ). First, lipoproteins contain a lipid moiety linked to their N-terminal Cys residue.…”

Section: Discussionmentioning

confidence: 99%

A Conserved Class II Type Thioester Domain-Containing Adhesin Is Required for Efficient Conjugation in Bacillus subtilis

Gago-Córdoba

Val-Calvo

Abia

et al. 2021

mBio

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Conjugation, the process by which a DNA element is transferred from a donor to a recipient cell, is the main horizontal gene transfer route responsible for the spread of antibiotic resistance and virulence genes. Contact between a donor and a recipient cell is a prerequisite for conjugation, because conjugative DNA is transferred into the recipient via a channel connecting the two cells. Conjugative elements encode proteins dedicated to facilitating the recognition and attachment to recipient cells, also known as mating pair formation. A subgroup of the conjugative elements is able to mediate efficient conjugation during planktonic growth, and mechanisms facilitating mating pair formation will be particularly important in these cases. Conjugative elements of Gram-negative bacteria encode conjugative pili, also known as sex pili, some of which are retractile. Far less is known about mechanisms that promote mating pair formation in Gram-positive bacteria. The conjugative plasmid pLS20 of the Gram-positive bacterium Bacillus subtilis allows efficient conjugation in liquid medium. Here, we report the identification of an adhesin gene in the pLS20 conjugation operon. The N-terminal region of the adhesin contains a class II type thioester domain (TED) that is essential for efficient conjugation, particularly in liquid medium. We show that TED-containing adhesins are widely conserved in Gram-positive bacteria, including pathogens where they often play crucial roles in pathogenesis. Our study is the first to demonstrate the involvement of a class II type TED-containing adhesin in conjugation. IMPORTANCE Bacterial resistance to antibiotics has become a serious health care problem. The spread of antibiotic resistance genes between bacteria of the same or different species is often mediated by a process named conjugation, where a donor cell transfers DNA to a recipient cell through a connecting channel. The first step in conjugation is recognition and attachment of the donor to a recipient cell. Little is known about this first step, particularly in Gram-positive bacteria. Here, we show that the conjugative plasmid pLS20 of Bacillus subtilis encodes an adhesin protein that is essential for effective conjugation. This adhesin protein has a structural organization similar to adhesins produced by other Gram-positive bacteria, including major pathogens, where the adhesins serve in attachment to host tissues during colonization and infection. Our findings may thus also open novel avenues to design drugs that inhibit the spread of antibiotic resistance by blocking the first recipient-attachment step in conjugation.

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Section: Discussionmentioning

confidence: 99%

A Conserved Class II Type Thioester Domain-Containing Adhesin Is Required for Efficient Conjugation in Bacillus subtilis

Gago-Córdoba

Val-Calvo

Abia

et al. 2021

mBio

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“…pyogenes and M. tuberculosis [12,16]. Lipoproteins are potent inducers of the host inflammatory responses through TLR2 receptors, and lipoprotein-rich MVs from M. tuberculosis and C. perfringens activate macrophages, leading to the release of inflammatory cytokines [28,40,56]. In L. monocytogenes, pheromone cAD1, the homologue of pheromone cAD1 lipoprotein that is enriched in enterococcal MVs, enhances bacterial escape from host cell vacuoles and bacterial virulence [57].…”

Section: Discussionmentioning

confidence: 99%

The composition and function ofEnterococcus faecalismembrane vesicles

Afonina

Tien

Nair

et al. 2021

Preprint

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Membrane vesicles (MVs) contribute to various biological processes in bacteria, including virulence factor delivery, host immune evasion, and cross-species communication. MVs are frequently being discharged from the surface of both Gram-negative and Gram-positive bacteria during growth. In some Gram-positive bacteria, genes affecting MV biogenesis have been identified, but the mechanism of MV formation is unknown. In Enterococcus faecalis, a causative agent of life-threatening bacteraemia and endocarditis, neither mechanisms of MV formation nor their role in virulence has been examined. Since MVs of many bacterial species are implicated in host-pathogen interactions, biofilm formation, horizontal gene transfer, and virulence factor secretion in other species, we sought to identify, describe, and functionally characterize MVs from E. faecalis. Here we show that E. faecalis releases MVs that possess unique lipid and protein profiles, distinct from the intact cell membrane, and are enriched in lipoproteins. MVs of E. faecalis are specifically enriched in unsaturated lipids that might provide membrane flexibility to enable MV formation, providing the first insights into the mechanism of MV formation in this Gram-positive organism.

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“…The hydrophobic nature of the acyl groups serves as a membrane anchor for the lipoprotein (17). In Gram-negative bacteria, lipoproteins reside in both the cytoplasmic and outer membranes, while in Gram-positive bacteria they are anchored in the outer leaflet of the cytoplasmic membrane and the protein portion may extend into the cell wall and beyond (18).…”

Section: Introductionmentioning

confidence: 99%

“…Lipoprotein genes are estimated to comprise 1-3% to all genes in bacterial genomes (18). While many lipoproteins have been identified and experimentally validated, others are putatively identified using predictive software, thus their functions remain unknown (19).…”

Section: Introductionmentioning

confidence: 99%

“…While many lipoproteins have been identified and experimentally validated, others are putatively identified using predictive software, thus their functions remain unknown (19). A recent bioinformatic evaluation of Staphylococcal lipoproteins in the MRSA strain USA300 identified 67 lipoproteins, comprising 2.57% of all genes (18). When grouped by function, 25 of the 67 lipoproteins were implicated in ion (notably iron) and nutrient transport, 8 were ascribed miscellaneous functions including sex pheromone biosynthesis, respiration, chaperone-folding, and protein translocation and 15 were classified as tandem lipoproteins, of which 9 are “lipoprotein-like” lipoproteins, known to play a role in host cell invasion (16).…”

Section: Introductionmentioning

confidence: 99%

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Mutation of lipoprotein processing pathway genelspAor inhibition of LspA activity by globomycin increases MRSA resistance to β-lactam antibiotics

Fingleton

Zeden

Cendejas-Bueno

et al. 2021

Preprint

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The Staphylococcus aureus cell envelope comprises numerous components, including peptidoglycan (PG), wall teichoic acids (WTA), lipoteichoic acids (LTA), targeted by antimicrobial drugs. MRSA resistance to methicillin is mediated by the mecA-encoded β-lactam-resistant transpeptidase, penicillin binding protein 2a (PBP2a). However, PBP2a-dependent β-lactam resistance is also modulated by the activity of pathways involved in the regulation or biosynthesis of PG, WTA or LTA. Here, we report that mutation of the lipoprotein signal peptidase II gene, lspA, from the lipoprotein processing pathway, significantly increased β-lactam resistance in MRSA. Mutation of lgt, which encodes diacylglycerol transferase (Lgt) responsible for synthesis of the LspA substrate did not impact beta-lactam susceptibility. Consistent with previous reports, lgt and lspA mutations impaired growth in chemically defined media, but not in complex broth. MRSA exposure to the LspA inhibitor globomycin also increased β-lactam resistance. Mutation of lgt in an lspA background restored β-lactam resistance to wild type. The lspA mutation had no effect on PBP2a expression, PG composition or autolytic activity indicating a potential role for WTA or LTA. The lspA and lgt mutants exhibited marginally increased resistance to the D-alanine pathway inhibitor D-cycloserine. In addition, mutation of lgt and multicopy lspA expression, but not mutation of lspA, significantly increased susceptibility to the lipoteichoic acid synthase inhibitor Congo red revealing complex interplay between lipoprotein processing mutations and the expression/stability of cell surface glycopolymers. These findings indicate that accumulation of the LspA substrate, diacylglyceryl lipoprotein, increases MRSA resistance to β-lactam antibiotics through impacts on cell envelope components other than PG.

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Lipoproteins in Gram-Positive Bacteria: Abundance, Function, Fitness

Cited by 50 publications

References 125 publications

A Conserved Class II Type Thioester Domain-Containing Adhesin Is Required for Efficient Conjugation in Bacillus subtilis

A Conserved Class II Type Thioester Domain-Containing Adhesin Is Required for Efficient Conjugation in Bacillus subtilis

The composition and function ofEnterococcus faecalismembrane vesicles

Mutation of lipoprotein processing pathway genelspAor inhibition of LspA activity by globomycin increases MRSA resistance to β-lactam antibiotics

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