scholarly journals Streptococcal Lancefield polysaccharides are critical cell wall determinants for human group IIA secreted phospholipase A2 to exert its bactericidal effects

2018 ◽  
Author(s):  
Vincent P. van Hensbergen ◽  
Elin Movert ◽  
Vincent de Maat ◽  
Christian Lüchtenborg ◽  
Yoann Le Breton ◽  
...  
Keyword(s):  
Cell Wall ◽  
Phospholipase A ◽  
Human Pathogens ◽  
Human Group ◽  
Gram Positive ◽  
Innate Defense ◽  
Gram Positive Bacteria ◽  
Group A ◽  
Group B ◽  
Peptidoglycan Layer

AbstractHuman Group IIA secreted phospholipase A2(hGIIA) is an acute phase protein with bactericidal activity against Gram-positive bacteria. Infection models in hGIIA transgenic mice have suggested the importance of hGIIA as an innate defense mechanism against the human pathogens Group AStreptococcus(GAS) and Group BStreptococcus(GBS). Compared to other Gram-positive bacteria, GAS is remarkably resistant to hGIIA activity. To identify GAS resistance mechanisms, we exposed a highly saturated GAS M1 transposon library to recombinant human hGIIA and compared relative mutant abundance with library input through transposon-sequencing (Tn-seq). Based on transposon prevalence in the output library, we identified nine genes, includingdltAandlytR,conferring increased hGIIA susceptibility. In addition, seven genes conferred increased hGIIA resistance, which included two genes,gacHandgacIthat are located within the Group A Carbohydrate (GAC) gene cluster. Using GAS 5448 wild-type and the isogenicgacImutant and gacI-complemented strains, we demonstrate that loss of the GACN-acetylglucosamine (GlcNAc) side chain in theΔgacImutant increases hGIIA resistance approximately 10-fold, a phenotype that is conserved across different GAS serotypes. Increased resistance is associated with delayed penetration of hGIIA through the cell wall. Correspondingly, loss of the Lancefield Group B Carbohydrate (GBC) rendered GBS significantly more resistant to hGIIA-mediated killing. This suggests that the streptococcal Lancefield antigens, which are critical determinants for streptococcal physiology and virulence, are required for the human bactericidal enzyme hGIIA to exert its bactericidal function.Author summaryThe human immune system is capable of killing invading bacteria by secreting antimicrobial proteins. Cationic human Group IIA secreted phospholipase A2(hGIIA) is especially effective against Gram-positive bacteria by degrading the bacterial membrane. HGIIA requires binding to negatively charged surface structures before it can penetrate through the thick peptidoglycan layer and reach the target phospholipid membrane. HGIIA is constitutively expressed at high concentrations at sites of possible bacterial entry, e.g. in tears, skin and small intestine. In serum, normal concentrations are low but can increase up to 1,000-fold upon inflammation or infection.In vitro,ex vivoandin vivoexperiments suggest an important role for hGIIA in defense against two human pathogens, Group A and Group BStreptococcus(GAS, GBS). We demonstrate that the Lancefield cell wall polysaccharides that are expressed by these bacteria, the Group A Carbohydrate (GAC) for GAS and the Group B Carbohydrate (GBC) for GBS, are required for optimal hGIIA bactericidal efficacy by facilitating penetration through the peptidoglycan layer. Given the increased hGIIA resistance of antigen-modified or antigen-deficient streptococci, it will be of interest to determine potential regulatory mechanisms regarding expression of streptococcal Lancefield polysaccharides.

scholarly journals The Relevance of IL-1-Signaling in the Protection against Gram-Positive Bacteria

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 132
Author(s):  
Angelina Midiri ◽  
Giuseppe Mancuso ◽  
Concetta Beninati ◽  
Elisabetta Gerace ◽  
Carmelo Biondo
Keyword(s):  
Host Defense ◽  
Group A Streptococcus ◽  
Bacterial Species ◽  
Interleukin 1 ◽  
Group B Streptococcus ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Group A ◽  
Group B ◽  
Deficient Mice

Previous studies performed using a model of group B streptococcus (GBS)-induced peritoneal inflammation indicate that the interleukin-1 receptor (IL-1R) family plays an important role in the innate host defense against this encapsulated Gram-positive bacteria. Since the role of IL-1-dependent signaling in peritoneal infections induced by other Gram-positive bacteria is unknown, in the present study we sought to investigate the contribution of IL-1R signaling in host defenses against Streptococcus pyogenes (group A streptococcus or GAS) or Staphylococcus aureus, two frequent and global human Gram-positive extracellular pathogens. We analyzed here the outcome of GAS or S. aureus infection in IL-1R-deficient mice. After inoculated intraperitoneal (i.p.) inoculation with group A Streptococcus or S. aureus, all the wild-type (WT) control mice survived the challenge, while, respectively, 63% or 50% of IL-1-defective mice died. Lethality was due to the ability of both bacterial species to replicate and disseminate to the target organs of IL-1R-deficient mice. Moreover, the experimental results indicate that IL-1 signaling promotes the production of leukocyte attractant chemokines CXCL-1 and CXCL-2 and recruitment of neutrophils to bacterial infection sites. Accordingly, the reduced neutrophil recruitment in IL-1R-deficient mice was linked with decreased production of neutrophil chemokines. Collectively, our findings indicate that IL-1 signaling, as previously showed in host defense against GBS, plays a fundamental role also in controlling the progression and outcome of GAS or S. aureus disease.

scholarly journals In Vitro Activities of Two Ketolides, HMR 3647 and HMR 3004, against Gram-Positive Bacteria

1999 ◽  
Vol 43 (4) ◽  
pp. 930-936 ◽  
Author(s):  
Kumthorn Malathum ◽  
Teresa M. Coque ◽  
Kavindra V. Singh ◽  
Barbara E. Murray
Keyword(s):  
Dilution Method ◽  
Agar Dilution Method ◽  
Group A Streptococci ◽  
Group B Streptococci ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Streptococci Group B ◽  
Group A ◽  
Group B

ABSTRACT The in vitro activities of two new ketolides, HMR 3647 and HMR 3004, were tested by the agar dilution method against 280 strains of gram-positive bacteria with different antibiotic susceptibility profiles, including Staphylococcus aureus,Enterococcus faecalis, Enterococcus faecium,Streptococcus spp. (group A streptococci, group B streptococci, Streptococcus pneumoniae, and alpha-hemolytic streptococci). Seventeen erythromycin-susceptible (Ems), methicillin-susceptible S. aureus strains were found to have HMR 3647 and HMR 3004 MICs 4- to 16-fold lower than those of erythromycin (MIC at which 50% of isolates were inhibited [MIC50] [HMR 3647 and HMR 3004], 0.03 μg/ml; range, 0.03 to 0.06 μg/ml; MIC50 [erythromycin], 0.25 μg/ml; range, 0.25 to 0.5 μg/ml). All methicillin-resistant S. aureus strains tested were resistant to erythromycin and had HMR 3647 and HMR 3004 MICs of >64 μg/ml. The ketolides were slightly more active against E. faecalis than against E. faecium, and MICs for individual strains varied with erythromycin susceptibility. The MIC50s of HMR 3647 and HMR 3004 against Ems enterococci (MIC ≤ 0.5 μg/ml) and those enterococcal isolates with erythromycin MICs of 1 to 16 μg/ml were 0.015 μg/ml. E. faecalis strains that had erythromycin MICs of 128 to >512 μg/ml showed HMR 3647 MICs in the range of 0.03 to 16 μg/ml and HMR 3004 MICs in the range of 0.03 to 64 μg/ml. In the group of E. faecium strains for which MICs of erythromycin were ≥512 μg/ml, MICs of both ketolides were in the range of 1 to 64 μg/ml, with almost all isolates showing ketolide MICs of ≤16 μg/ml. The ketolides were also more active than erythromycin against group A streptococci, group B streptococci,S. pneumoniae, rhodococci, leuconostocs, pediococci, lactobacilli, and diphtheroids. Time-kill studies showed bactericidal activity against one strain of S. aureus among the four strains tested. The increased activity of ketolides against gram-positive bacteria suggests that further study of these agents for possible efficacy against infections caused by these bacteria is warranted.

scholarly journals A study of surgical site infections with and without the use of pre-operative antibiotics

2019 ◽  
Vol 6 (10) ◽  
pp. 3806
Author(s):  
Arun Kumar Gupta ◽  
Seema Mittal ◽  
Tejinder Singh Dall ◽  
Darpan Bansal
Keyword(s):  
Surgical Site Infection ◽  
Surgical Site Infections ◽  
Site Infection ◽  
Medical Sciences ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Group A ◽  
Group B ◽  
Clean Contaminated

Background: In spite of advances in infection control, infection still remains the major limitor of surgical horizons. After urinary tract infection, surgical site infection is a main factor contributing to morbidity and mortality.Methods: The present study was carried out in the department of General Surgery and Microbiology at Shri Guru Ram Das Institute of Medical Sciences and Research, Vallah, Sri Amritsar. In this study 100 patients were selected undergoing clean or clean contaminated surgeries out of which 50 patients were not given pre-operative antibiotics (first group) and remaining 50 patients (second group) were given preoperative antibiotics.Results: Sample consisted of 100 patients with mean age of patients was 36.97 years. Total number of males was 57 and females were 43. 25 (50%) of patients who had not received prophylaxis developed SSI (group A) and 28 (56%) patients who received prophylaxis developed SSI (group B). Most common bacteria isolated from SSI was Staphylococcus aureus for both the groups. 10 (52.63%) Gram positive bacteria were isolated from microscopic examination of infected sample (A) and 25 (73.52%) were gram negative bacteria. 25 (73.52%) were Gram positive bacteria in group (b) and 9 (26.47%) were Gram negative isolates.Conclusions: It can be concluded from the present study that there is no need to give antibiotic prophylaxis prior to surgery in order to reduce the incidence of surgical site infection.

Ultrastructure of the cell wall and the mechanism of cellular division of a Gram-variable coccus

1971 ◽  
Vol 17 (3) ◽  
pp. 421-424 ◽  
Author(s):  
H. E. Gilleland Jr. ◽  
I. L. Roth ◽  
R. G. Eagon
Keyword(s):  
Cell Wall ◽  
Outer Membrane ◽  
Ultrastructural Study ◽  
Cytoplasmic Membrane ◽  
Gram Positive ◽  
Cellular Division ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Isolated Cell ◽  
Peptidoglycan Layer

An ultrastructural study of a Gram-variable coccus was carried out. The cell wall of this microorganism was composed of an inner peptidoglycan layer, a middle electron-transparent compartment, and an undulating trilayered outer membrane. This microorganism also possessed numerous mesosomes which were simple bulb-like invaginations of the cytoplasmic membrane. The mechanism of cellular division involved the formation of a septum by the cytoplasmic membrane and the inner layer of the cell wall. Membranous structures were associated with the developing septum throughout the process. The outer membrane of the cell wall did not invaginate with the inner layer but reformed as the completed septum began to split. In isolated cell wall preparations, no 2-keto-3-deoxyoctonate or heptose could be detected. It is suggested that the Gram-variable cocci previously classified as micrococci may represent a group that is intermediate between true Gram-negative and Gram-positive bacteria.

Influence of Cell Wall Composition on the Fossilisation of Bacteria and the Implications for the Search for Early Life Forms

1997 ◽  
Vol 161 ◽  
pp. 491-504 ◽  
Author(s):  
Frances Westall
Keyword(s):  
Cell Wall ◽  
Life Forms ◽  
Cation Binding ◽  
Positive Bacterium ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Transmission Electron ◽  
Hydrothermal Sediments ◽  
Identification Of Bacteria ◽  
The Difference

AbstractThe oldest cell-like structures on Earth are preserved in silicified lagoonal, shallow sea or hydrothermal sediments, such as some Archean formations in Western Australia and South Africa. Previous studies concentrated on the search for organic fossils in Archean rocks. Observations of silicified bacteria (as silica minerals) are scarce for both the Precambrian and the Phanerozoic, but reports of mineral bacteria finds, in general, are increasing. The problems associated with the identification of authentic fossil bacteria and, if possible, closer identification of bacteria type can, in part, be overcome by experimental fossilisation studies. These have shown that not all bacteria fossilise in the same way and, indeed, some seem to be very resistent to fossilisation. This paper deals with a transmission electron microscope investigation of the silicification of four species of bacteria commonly found in the environment. The Gram positiveBacillus laterosporusand its spore produced a robust, durable crust upon silicification, whereas the Gram negativePseudomonas fluorescens, Ps. vesicularis, andPs. acidovoranspresented delicately preserved walls. The greater amount of peptidoglycan, containing abundant metal cation binding sites, in the cell wall of the Gram positive bacterium, probably accounts for the difference in the mode of fossilisation. The Gram positive bacteria are, therefore, probably most likely to be preserved in the terrestrial and extraterrestrial rock record.

Microanatomy of the Periplasm of Bacillus Licheniformis

1971 ◽  
Vol 29 ◽  
pp. 262-263
Author(s):  
B.K. Ghosh
Keyword(s):  
Cell Wall ◽  
Plasma Membrane ◽  
Bacillus Licheniformis ◽  
External Environment ◽  
Permeability Barrier ◽  
Periplasmic Space ◽  
Modified Technique ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria

Periplasm of bacteria is the space outside the permeability barrier of plasma membrane but enclosed by the cell wall. The contents of this special milieu exterior could be regulated by the plasma membrane from the internal, and by the cell wall from the external environment of the cell. Unlike the gram-negative organism, the presence of this space in gram-positive bacteria is still controversial because it cannot be clearly demonstrated. We have shown the importance of some periplasmic bodies in the secretion of penicillinase from Bacillus licheniformis.In negatively stained specimens prepared by a modified technique (Figs. 1 and 2), periplasmic space (PS) contained two kinds of structures: (i) fibrils (F, 100 Å) running perpendicular to the cell wall from the protoplast and (ii) an array of vesicles of various sizes (V), which seem to have evaginated from the protoplast.

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.

Influence of the cell wall on ciprofloxacin susceptibility in selected wild-type Gram-negative and Gram-positive bacteria

2004 ◽  
Vol 23 (6) ◽  
pp. 627-630 ◽  
Author(s):  
Mercedes Berlanga ◽  
M.Teresa Montero ◽  
Jordi Hernández-Borrell ◽  
Miquel Viñas
Keyword(s):  
Cell Wall ◽  
Wild Type ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria

scholarly journals Structures of the surface exposed proteins of Gram positive bacteria

2014 ◽  
Vol 70 (a1) ◽  
pp. C432-C432
Author(s):  
George Minasov ◽  
Salvatore Nocadello ◽  
Ekaterina Filippova ◽  
Andrei Halavaty ◽  
Wayne Anderson
Keyword(s):  
Cell Wall ◽  
Infectious Diseases ◽  
Bacillus Anthracis ◽  
Structural Genomics ◽  
Drug Targets ◽  
Morphological Changes ◽  
Target Selection ◽  
Surface Proteins ◽  
Human Pathogens ◽  
Gram Positive

The Center for Structural Genomics for Infectious Diseases (CSGID) applies structural genomics approaches to biomedically important proteins from human pathogens. It also provides the infectious disease community with a high throughput pipeline for structure determination that carries out all steps of the process, from target selection through structure deposition. Target proteins include drug targets, essential enzymes, virulence factors and vaccine candidates. The CSGID has deposited over 680 structures in the Protein Data Bank. The proteins that are exposed on the surface of Gram positive bacterial pathogens (including Staphylococcus aureus, Bacillus anthracis, Listeria monocytogenes, Streptococcus species and Clostridium species) have been one focus area for the CSGID. So far, the structures of more than 55 of these proteins have been determined. The surface proteins are important in the interactions between the pathogen and its host, but many of them are as yet functionally uncharacterized. Among the examples that will be presented is the Bacillus anthracis SpoIID protein. SpoIID is part of a coordinated cell wall degradation machine that is essential for sporulation and the morphological changes involved. It represents a new family of lytic transglycosylases that degrade the glycan strands of the peptidoglycan cell wall. The two active site clefts in the dimeric enzyme include residues from both subunits, suggesting that the dimer is required for activity. This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contracts No. HHSN272200700058C and HHSN272201200026C.

scholarly journals Turnover of the Cell Wall of Gram-positive Bacteria

1971 ◽  
Vol 246 (6) ◽  
pp. 1820-1827 ◽  
Author(s):  
John Mauck ◽  
Lawrence Chan ◽  
Luis Glaser
Keyword(s):  
Cell Wall ◽  
Gram Positive ◽  
Gram Positive Bacteria
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