scholarly journals Streptococcus pneumoniae, S. mitis, and S. oralis produce a phosphatidylglycerol-dependent, ltaS-independent glycerophosphate-linked glycolipid

2020 ◽  
Author(s):  
Yahan Wei ◽  
Luke R. Joyce ◽  
Ashley M. Wall ◽  
Ziqiang Guan ◽  
Kelli L. Palmer
Keyword(s):  
Streptococcus Pneumoniae ◽  
Lipoteichoic Acid ◽  
Growth Defect ◽  
Type I ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Type Iv ◽  
Biosynthetic Precursor ◽  
Increased Sensitivity ◽  
Host Microbe Interactions

AbstractLipoteichoic acid (LTA) is a cell surface polymer of Gram-positive bacteria. LTA participates in host-microbe interactions including modulation of host immune reactions. It was previously reported that the major human pathogen Streptococcus pneumoniae and the closely related oral commensals S. mitis and S. oralis produce Type IV LTAs. Herein, using liquid chromatography/mass spectrometry (LC/MS)-based lipidomic analysis, we found that in addition to Type IV LTA biosynthetic precursors, S. mitis, S. oralis, and S. pneumoniae also produce glycerophosphate (Gro-P)-linked dihexosyl-diacylglycerol (DAG), which is a biosynthetic precursor of Type I LTA. Mutants in cdsA and pgsA produce dihexosyl-DAG but lack (Gro-P)-dihexosyl-DAG, indicating that the Gro-P moiety is derived from phosphatidylglycerol (PG), whose biosynthesis requires these genes. S. mitis, but neither S. pneumoniae nor S. oralis, encodes an ortholog of the PG-dependent Type I LTA synthase, ltaS. By heterologous expression analyses, we confirmed that S. mitis ltaS confers poly-(Gro-P) synthesis in both Escherichia coli and Staphylococcus aureus, and that S. mitis ltaS can rescue the severe growth defect of a S. aureus ltaS mutant. However, despite these observations, we do not detect a poly-(Gro-P) polymer in S. mitis using an anti-Type I LTA antibody. Moreover, (Gro-P)-linked dihexosyl-DAG is still synthesized by a S. mitis ltaS mutant, demonstrating that S. mitis LtaS does not catalyze the transfer of Gro-P from PG to dihexosyl-DAG. Finally, a S. mitis ltaS mutant has increased sensitivity to human serum, demonstrating that ltaS confers a beneficial but currently undefined function in S. mitis. Overall, our results demonstrate that S. mitis, S. pneumoniae, and S. oralis produce a (Gro-P)-linked glycolipid via a PG-dependent, ltaS-independent mechanism.ImportanceLTA is an important cell wall component synthesized by Gram-positive bacteria. Disruption of LTA production can confer severe physiological defects and attenuation of virulence. We report here the detection of a biosynthetic precursor of Type I LTA, in addition to the previously characterized Type IV LTA, in the total lipid extracts of S. pneumoniae, S. oralis, and S. mitis. Our results indicate that a novel mechanism is responsible for producing the Type I LTA intermediate. Our results are significant because they identify a novel feature of S. pneumoniae, S. oralis, and S. mitis glycolipid biology.

scholarly journals Protection from Lethal Gram-Positive Infection by Macrophage Scavenger Receptor–Dependent Phagocytosis

2000 ◽  
Vol 191 (1) ◽  
pp. 147-156 ◽  
Author(s):  
Christian A. Thomas ◽  
Yongmei Li ◽  
Tatsuhiko Kodama ◽  
Hiroshi Suzuki ◽  
Samuel C. Silverstein ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Critical Role ◽  
Scavenger Receptor ◽  
Lipoteichoic Acid ◽  
Peritoneal Macrophages ◽  
Type I ◽  
Dependent Manner ◽  
Gram Positive ◽  
Gram Positive Bacteria

Infections with gram-positive bacteria are a major cause of morbidity and mortality in humans. Opsonin-dependent phagocytosis plays a major role in protection against and recovery from gram-positive infections. Inborn and acquired defects in opsonin generation and/or recognition by phagocytes are associated with an increased susceptibility to bacterial infections. In contrast, the physiological significance of opsonin-independent phagocytosis is unknown. Type I and II class A scavenger receptors (SR-AI/II) recognize a variety of polyanions including bacterial cell wall products such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA), suggesting a role for SR-AI/II in innate immunity to bacterial infections. Here, we show that SR-AI/II–deficient mice (MSR-A−/−) are more susceptible to intraperitoneal infection with a prototypic gram-positive pathogen, Staphylococcus aureus, than MSR-A+/+ control mice. MSR-A−/− mice display an impaired ability to clear bacteria from the site of infection despite normal killing of S. aureus by neutrophils and die as a result of disseminated infection. Opsonin-independent phagocytosis of gram-positive bacteria by MSR-A−/− macrophages is significantly decreased although their phagocytic machinery is intact. Peritoneal macrophages from control mice phagocytose a variety of gram-positive bacteria in an SR-AI/II–dependent manner. Our findings demonstrate that SR-AI/II mediate opsonin-independent phagocytosis of gram-positive bacteria, and provide the first evidence that opsonin-independent phagocytosis plays a critical role in host defense against bacterial infections in vivo.

scholarly journals The Cell Wall Polymer Lipoteichoic Acid Becomes Nonessential inStaphylococcus aureusCells Lacking the ClpX Chaperone

mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
Kristoffer T. Bæk ◽  
Lisa Bowman ◽  
Charlotte Millership ◽  
Mia Dupont Søgaard ◽  
Volkhard Kaever ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cell Division ◽  
Lipoteichoic Acid ◽  
Growth Defect ◽  
Gram Positive ◽  
Functional Connection ◽  
Antibiotic Resistant ◽  
Gram Positive Bacteria ◽  
Autolytic Activity

ABSTRACTLipoteichoic acid (LTA) is an important cell wall component of Gram-positive bacteria and a promising target for the development of vaccines and antimicrobial compounds againstStaphylococcus aureus. Here we demonstrate that mutations in the conditionally essentialltaS(LTA synthase) gene arise spontaneously in anS. aureusmutant lacking the ClpX chaperone. A wide variety ofltaSmutations were selected, and among these, a substantial portion resulted in premature stop codons and other changes predicted to abolish LtaS synthesis. Consistent with this assumption, theclpX ltaSdouble mutants did not produce LTA, and genetic analyses confirmed that LTA becomes nonessential in the absence of the ClpX chaperone. In fact, inactivation ofltaSalleviated the severe growth defect conferred by theclpXdeletion. Microscopic analyses showed that the absence of ClpX partly alleviates the septum placement defects of an LTA-depleted strain, while other phenotypes typical of LTA-negativeS. aureusmutants, including increased cell size and decreased autolytic activity, are retained. In conclusion, our results indicate that LTA has an essential role in septum placement that can be bypassed by inactivating the ClpX chaperone.IMPORTANCELipoteichoic acid is an essential component of theStaphylococcus aureuscell envelope and an attractive target for the development of vaccines and antimicrobials directed against antibiotic-resistant Gram-positive bacteria such as methicillin-resistantS. aureusand vancomycin-resistant enterococci. In this study, we showed that the lipoteichoic acid polymer is essential for growth ofS. aureusonly as long as the ClpX chaperone is present in the cell. Our results indicate that lipoteichoic acid and ClpX play opposite roles in a pathway that controls two key cell division processes inS. aureus, namely, septum formation and autolytic activity. The discovery of a novel functional connection in the genetic network that controls cell division inS. aureusmay expand the repertoire of possible strategies to identify compounds or compound combinations that kill antibiotic-resistantS. aureus.

scholarly journals Alanylated lipoteichoic acid primer in Bacillus subtilis

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 155 ◽  
Author(s):  
Yu Luo
Keyword(s):  
Bacillus Subtilis ◽  
Lipoteichoic Acid ◽  
Head Group ◽  
Host Immune System ◽  
Type I ◽  
Bacterial Survival ◽  
Gram Positive Bacteria ◽  
Type Iv ◽  
Glycolipid Anchor ◽  
Group D

Lipoteichoic acid is a major lipid-anchored polymer in Gram-positive bacteria such asBacillus subtilis. This polymer typically consists of repeating phosphate-containing units and therefore has a predominant negative charge. The repeating units are attached to a glycolipid anchor which has a diacylglycerol (DAG) moiety attached to a dihexopyranose head group. D-alanylation is known as the major modification of type I and type IV lipoteichoic acids, which partially neutralizes the polymer and plays important roles in bacterial survival and resistance to the host immune system. The biosynthesis pathways of the glycolipid anchor and lipoteichoic acid have been fully characterized. However, the exact mechanism of D-alanyl transfer from the cytosol to cell surface lipoteichoic acid remains unclear. Here I report the use of mass spectrometry in the identification of possible intermediate species in the biosynthesis and D-alanylation of lipoteichoic acid: the glycolipid anchor, nascent lipoteichoic acid primer with one phosphoglycerol unit, as well as mono- and di-alanylated forms of the lipoteichoic acid primer. Monitoring these species as well as the recently reported D-alanyl-phosphatidyl glycerol should aid in shedding light on the mechanism of the D-alanylation pathway of lipoteichoic acid.

scholarly journals Streptococcus gordonii Type I Lipoteichoic Acid Contributes to Surface Protein Biogenesis

mSphere ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Bruno P. Lima ◽  
Kelvin Kho ◽  
Brittany L. Nairn ◽  
Julia R. Davies ◽  
Gunnel Svensäter ◽  
...  
Keyword(s):  
Cell Surface ◽  
Biofilm Formation ◽  
Cell Envelope ◽  
Surface Protein ◽  
Lipoteichoic Acid ◽  
Type I ◽  
Streptococcus Gordonii ◽  
Gram Positive ◽  
Content Type ◽  
Gram Positive Bacteria

ABSTRACT Lipoteichoic acid (LTA) is an abundant polymer of the Gram-positive bacterial cell envelope and is essential for many species. Whereas the exact function of LTA has not been elucidated, loss of LTA in some species affects hydrophobicity, biofilm formation, and cell division. Using a viable LTA-deficient strain of the human oral commensal Streptococcus gordonii, we demonstrated that LTA plays an important role in surface protein presentation. Cell wall fractions derived from the wild-type and LTA-deficient strains of S. gordonii were analyzed using label-free mass spectroscopy. Comparisons showed that the abundances of many proteins differed, including (i) SspA, SspB, and S. gordonii 0707 (SGO_0707) (biofilm formation); (ii) FtsE (cell division); (iii) Pbp1a and Pbp2a (cell wall biosynthesis and remodeling); and (iv) DegP (envelope stress response). These changes in cell surface protein presentation appear to explain our observations of altered cell envelope homeostasis, biofilm formation, and adhesion to eukaryotic cells, without affecting binding and coaggregation with other bacterial species, and provide insight into the phenotypes revealed by the loss of LTA in other species of Gram-positive bacteria. We also characterized the chemical structure of the LTA expressed by S. gordonii. Similarly to Streptococcus suis, S. gordonii produced a complex type I LTA, decorated with multiple d-alanylations and glycosylations. Hence, the S. gordonii LTA appears to orchestrate expression and presentation of cell surface-associated proteins and functions. IMPORTANCE Discovered over a half-century ago, lipoteichoic acid (LTA) is an abundant polymer found on the surface of Gram-positive bacteria. Although LTA is essential for the survival of many Gram-positive species, knowledge of how LTA contributes to bacterial physiology has remained elusive. Recently, LTA-deficient strains have been generated in some Gram-positive species, including the human oral commensal Streptococcus gordonii. The significance of our research is that we utilized an LTA-deficient strain of S. gordonii to address why LTA is physiologically important to Gram-positive bacteria. We demonstrate that in S. gordonii, LTA plays an important role in the presentation of many cell surface-associated proteins, contributing to cell envelope homeostasis, cell-to-cell interactions in biofilms, and adhesion to eukaryotic cells. These data may broadly reflect a physiological role of LTA in Gram-positive bacteria.

scholarly journals Gram-positive bacteria cell wall-derived lipoteichoic acid induces inflammatory alveolar bone loss through prostaglandin E production in osteoblasts

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tsukasa Tominari ◽  
Ayumi Sanada ◽  
Ryota Ichimaru ◽  
Chiho Matsumoto ◽  
Michiko Hirata ◽  
...  
Keyword(s):  
Cell Wall ◽  
Bone Loss ◽  
Alveolar Bone ◽  
Osteoclast Differentiation ◽  
Lipoteichoic Acid ◽  
Alveolar Bone Loss ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria

AbstractPeriodontitis is an inflammatory disease associated with severe alveolar bone loss and is dominantly induced by lipopolysaccharide from Gram-negative bacteria; however, the role of Gram-positive bacteria in periodontal bone resorption remains unclear. In this study, we examined the effects of lipoteichoic acid (LTA), a major cell-wall factor of Gram-positive bacteria, on the progression of inflammatory alveolar bone loss in a model of periodontitis. In coculture of mouse primary osteoblasts and bone marrow cells, LTA induced osteoclast differentiation in a dose-dependent manner. LTA enhanced the production of PGE2 accompanying the upregulation of the mRNA expression of mPGES-1, COX-2 and RANKL in osteoblasts. The addition of indomethacin effectively blocked the LTA-induced osteoclast differentiation by suppressing the production of PGE2. Using ex vivo organ cultures of mouse alveolar bone, we found that LTA induced alveolar bone resorption and that this was suppressed by indomethacin. In an experimental model of periodontitis, LTA was locally injected into the mouse lower gingiva, and we clearly detected alveolar bone destruction using 3D-μCT. We herein demonstrate a new concept indicating that Gram-positive bacteria in addition to Gram-negative bacteria are associated with the progression of periodontal bone loss.

scholarly journals Mixed liposomes containing gram-positive bacteria lipids: Lipoteichoic acid (LTA) induced structural changes

2021 ◽  
Vol 199 ◽  
pp. 111551
Author(s):  
Bhavesh Bharatiya ◽  
Gang Wang ◽  
Sarah E. Rogers ◽  
Jan Skov Pedersen ◽  
Stephen Mann ◽  
...  
Keyword(s):  
Structural Changes ◽  
Lipoteichoic Acid ◽  
Gram Positive ◽  
Gram Positive Bacteria

scholarly journals In Vitro and In Vivo Activities of DA-7867, a New Oxazolidinone, against Aerobic Gram-Positive Bacteria

2005 ◽  
Vol 49 (6) ◽  
pp. 2498-2500 ◽  
Author(s):  
Eun Jeong Yoon ◽  
Yeong Woo Jo ◽  
Sung Hak Choi ◽  
Tae Ho Lee ◽  
Jae Keol Rhee ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Vancomycin Resistant Enterococci ◽  
Infection Models ◽  
Vancomycin Resistant

ABSTRACT In vitro and in vivo activities of DA-7867 were assessed against methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae. All isolates were inhibited by DA-7867 at ≤0.78 μg/ml, a four-times-lower concentration than that of inhibition by linezolid. For murine infection models, DA-7867 also exhibited greater efficacy than linezolid against all isolates tested.

scholarly journals A Type IV-Secretion-Like System Is Required for Conjugative DNA Transport of Broad-Host-Range Plasmid pIP501 in Gram-Positive Bacteria

2007 ◽  
Vol 189 (6) ◽  
pp. 2487-2496 ◽  
Author(s):  
Mohammad Y. Abajy ◽  
Jolanta Kopeć ◽  
Katarzyna Schiwon ◽  
Michal Burzynski ◽  
Mike Döring ◽  
...  
Keyword(s):  
Host Range ◽  
Sequence Similarity ◽  
Type Iv Secretion ◽  
Conjugative Plasmid ◽  
Computer Assisted ◽  
Transcriptional Level ◽  
Broad Host Range ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Type Iv

ABSTRACT Plasmid pIP501 has a very broad host range for conjugative transfer among a wide variety of gram-positive bacteria and gram-negative Escherichia coli. Functionality of the pIP501 transfer (tra) genes in E. coli was proven by pIP501 retrotransfer to Enterococcus faecalis (B. Kurenbach, C. Bohn, J. Prabhu, M. Abudukerim, U. Szewzyk, and E. Grohmann, Plasmid 50:86-93, 2003). The 15 pIP501 tra genes are organized in a single operon (B. Kurenbach, J. Kopeć, M. Mägdefrau, K. Andreas, W. Keller, C. Bohn, M. Y. Abajy, and E. Grohmann, Microbiology 152:637-645, 2006). The pIP501 tra operon is negatively autoregulated at the transcriptional level by the conjugative DNA relaxase TraA. Three of the 15 pIP501-encoded Tra proteins show significant sequence similarity to the Agrobacterium type IV secretion system proteins VirB1, VirB4, and VirD4. Here we report a comprehensive protein-protein interaction map of all of the pIP501-encoded Tra proteins determined by the yeast two-hybrid assay. Most of the interactions were verified in vitro by isolation of the protein complexes with pull-down assays. In conjunction with known or postulated functions of the pIP501-encoded Tra proteins and computer-assisted prediction of their cellular location, we propose a model for the first type IV-secretion-like system encoded by a conjugative plasmid from gram-positive bacteria.

scholarly journals phgABC, a Three-Gene Operon Required for Growth of Streptococcus pneumoniae in Hyperosmotic Medium and In Vivo

2004 ◽  
Vol 72 (8) ◽  
pp. 4579-4588 ◽  
Author(s):  
Jeremy S. Brown ◽  
Sarah M. Gilliland ◽  
Shilpa Basavanna ◽  
David W. Holden
Keyword(s):  
Streptococcus Pneumoniae ◽  
Mutant Strain ◽  
Compatible Solutes ◽  
Wild Type ◽  
Gram Positive Bacteria ◽  
Mutant Strains ◽  
Increased Sensitivity ◽  
Related Proteins ◽  
And Oxidative Stress

ABSTRACT To cause disease, bacterial pathogens need to be able to adapt to the physiological conditions found within the host, including an osmolality of approximately 290 mosmol kg−1. While investigating Streptococcus pneumoniae genes contained within pneumococcal pathogenicity island 1, we identified a three-gene operon of unknown function termed phgABC. PhgC has a domain with similarity to diacylglycerol kinases of eukaryotes and is the first described member of a family of related proteins found in many gram-positive bacteria. phgA and phgC mutant strains were constructed by insertional duplication mutagenesis and found to have impaired growth under conditions of high osmotic and oxidative stress. The compatible solutes proline and glycine betaine improved growth of the wild-type and the phgA mutant strains in hyperosmolar medium, and when analyzed by electron microscopy, the cellular morphology of the phgA mutant strain was unaffected by osmotic stress. The phgA and phgC mutant strains were reduced in virulence in models of both systemic and pulmonary infection. As the virulence of the phgA mutant strain was not restored in gp91phox−/− mice and the phgA and phgC mutant strains had reduced growth in both blood and serum, the reduced virulence of these strains is unlikely to be due to increased sensitivity to the respiratory burst of phagocytes but is, instead, due to impaired growth at physiological osmolality.

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