scholarly journals Multimodular Penicillin-Binding Proteins: An Enigmatic Family of Orthologs and Paralogs

1998 ◽  
Vol 62 (4) ◽  
pp. 1079-1093 ◽  
Author(s):  
Colette Goffin ◽  
Jean-Marie Ghuysen
Keyword(s):  
Amino Acid ◽  
Polypeptide Chain ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Full Size ◽  
Penicillin Binding Proteins ◽  
Gram Positive Bacteria ◽  
Class A ◽  
Class B ◽  
Resistance To Penicillin

SUMMARY The monofunctional penicillin-binding dd-peptidases and penicillin-hydrolyzing serine β-lactamases diverged from a common ancestor by the acquisition of structural changes in the polypeptide chain while retaining the same folding, three-motif amino acid sequence signature, serine-assisted catalytic mechanism, and active-site topology. Fusion events gave rise to multimodular penicillin-binding proteins (PBPs). The acyl serine transferase penicillin-binding (PB) module possesses the three active-site defining motifs of the superfamily; it is linked to the carboxy end of a non-penicillin-binding (n-PB) module through a conserved fusion site; the two modules form a single polypeptide chain which folds on the exterior of the plasma membrane and is anchored by a transmembrane spanner; and the full-size PBPs cluster into two classes, A and B. In the class A PBPs, the n-PB modules are a continuum of diverging sequences; they possess a five-motif amino acid sequence signature, and conserved dicarboxylic amino acid residues are probably elements of the glycosyl transferase catalytic center. The PB modules fall into five subclasses: A1 and A2 in gram-negative bacteria and A3, A4, and A5 in gram-positive bacteria. The full-size class A PBPs combine the required enzymatic activities for peptidoglycan assembly from lipid-transported disaccharide-peptide units and almost certainly prescribe different, PB-module specific traits in peptidoglycan cross-linking. In the class B PBPs, the PB and n-PB modules cluster in a concerted manner. A PB module of subclass B2 or B3 is linked to an n-PB module of subclass B2 or B3 in gram-negative bacteria, and a PB module of subclass B1, B4, or B5 is linked to an n-PB module of subclass B1, B4, or B5 in gram-positive bacteria. Class B PBPs are involved in cell morphogenesis. The three motifs borne by the n-PB modules are probably sites for module-module interaction and the polypeptide stretches which extend between motifs 1 and 2 are sites for protein-protein interaction. The full-size class B PBPs are an assortment of orthologs and paralogs, which prescribe traits as complex as wall expansion and septum formation. PBPs of subclass B1 are unique to gram-positive bacteria. They are not essential, but they represent an important mechanism of resistance to penicillin among the enterococci and staphylococci. Natural evolution and PBP- and β-lactamase-mediated resistance show that the ability of the catalytic centers to adapt their properties to new situations is limitless. Studies of the reaction pathways by using the methods of quantum chemistry suggest that resistance to penicillin is a road of no return.

scholarly journals Distinctive Binding of Avibactam to Penicillin-Binding Proteins of Gram-Negative and Gram-Positive Bacteria

2015 ◽  
Vol 60 (2) ◽  
pp. 752-756 ◽  
Author(s):  
Abdelhamid Asli ◽  
Eric Brouillette ◽  
Kevin M. Krause ◽  
Wright W. Nichols ◽  
François Malouin
Keyword(s):  
Binding Proteins ◽  
New Combination ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Penicillin Binding Proteins ◽  
Gram Positive Bacteria ◽  
Fixed Concentration ◽  
Competition Assays

ABSTRACTAvibactam is a novel non-β-lactam β-lactamase inhibitor that covalently acylates a variety of β-lactamases, causing inhibition. Although avibactam presents limited antibacterial activity, its acylation ability toward bacterial penicillin-binding proteins (PBPs) was investigated.Staphylococcus aureuswas of particular interest due to the reported β-lactamase activity of PBP4. The binding of avibactam to PBPs was measured by adding increasing concentrations to membrane preparations of a variety of Gram-positive and Gram-negative bacteria prior to addition of the fluorescent reagent Bocillin FL. Relative binding (measured here as the 50% inhibitory concentration [IC50]) to PBPs was estimated by quantification of fluorescence after gel electrophoresis. Avibactam was found to selectively bind to some PBPs. InEscherichia coli,Pseudomonas aeruginosa,Haemophilus influenzae, andS. aureus, avibactam primarily bound to PBP2, with IC50s of 0.92, 1.1, 3.0, and 51 μg/ml, respectively, whereas binding to PBP3 was observed inStreptococcus pneumoniae(IC50, 8.1 μg/ml). Interestingly, avibactam was able to significantly enhance labeling ofS. aureusPBP4 by Bocillin FL. In PBP competition assays withS. aureus, where avibactam was used at a fixed concentration in combination with varied amounts of ceftazidime, the apparent IC50of ceftazidime was found to be very similar to that determined for ceftazidime when used alone. In conclusion, avibactam is able to covalently bind to some bacterial PBPs. Identification of those PBP targets may allow the development of new diazabicyclooctane derivatives with improved affinity for PBPs or new combination therapies that act on multiple PBP targets.

The structure of β-lactamases

1980 ◽  
Vol 289 (1036) ◽  
pp. 321-331 ◽  
Keyword(s):  
Amino Acid ◽  
Sequence Analysis ◽  
Amino Acid Sequence ◽  
Homology Group ◽  
Gram Negative Bacteria ◽  
Sequence Determination ◽  
Present Evidence ◽  
Class A ◽  
Class B ◽  
Lactam Ring

The β-lactamases are widely distributed in both Gram-positive and Gram-negative bacteria. They all inactivate penicillins and cephalosporins by opening the β-lactam ring. Many varieties of the enzyme can be distinguished on the basis of their catalytic and molecular properties, but only amino acid sequence determination gives information upon which a molecular phylogeny can be based. The present evidence suggests that the β-lactamases have a polyphyletic origin. All the β-lactamases of currently known amino acid sequence belong to one homology group, here called class A enzymes. Class B consists of the mechanistically distinct Bacillus cereus β-lactamase II, which preliminary partial sequence analysis suggests to be structurally unrelated to the class A enzymes. It is predicted that sequence analysis will show that further classes will need to be created to account for particular β-lactamases of distinctive molecular and mechanistic properties.

scholarly journals Synthesis and Antimicrobial Activity of a New Series of Thiazolidine-2,4-diones Carboxamide and Amino Acid Derivatives

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 105 ◽  
Author(s):  
Rakia Abd Alhameed ◽  
Zainab Almarhoon ◽  
Sarah I. Bukhari ◽  
Ayman El-Faham ◽  
Beatriz G. de la Torre ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Amino Acid ◽  
Antifungal Activity ◽  
Fungal Isolate ◽  
Amino Acid Derivatives ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Antimicrobial And Antifungal Activity

Novel thiazolidine-2,4-dione carboxamide and amino acid derivatives were synthesized in excellent yield using OxymaPure/N,N′-diisopropylcarbodimide coupling methodology and were characterized by chromatographic and spectrometric methods, and elemental analysis. The antimicrobial and antifungal activity of these derivatives was evaluated against two Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), two-Gram negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and one fungal isolate (Candida albicans). Interestingly, several samples demonstrated weak to moderate antibacterial activity against Gram-negative bacteria, as well as antifungal activity. However, only one compound namely, 2-(5-(3-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetic acid, showed antibacterial activity against Gram-positive bacteria, particularly S. aureus.

scholarly journals Past and Present Perspectives on β-Lactamases

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Karen Bush
Keyword(s):  
Sequence Data ◽  
Amino Acid Sequences ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Penicillin Binding Proteins ◽  
Gram Positive Bacteria ◽  
Class A ◽  
Naturally Occurring ◽  
Clinical Community ◽  
Sequencing Studies

ABSTRACTβ-Lactamases, the major resistance determinant for β-lactam antibiotics in Gram-negative bacteria, are ancient enzymes whose origins can be traced back millions of years ago. These well-studied enzymes, currently numbering almost 2,800 unique proteins, initially emerged from environmental sources, most likely to protect a producing bacterium from attack by naturally occurring β-lactams. Their ancestors were presumably penicillin-binding proteins that share sequence homology with β-lactamases possessing an active-site serine. Metallo-β-lactamases also exist, with one or two catalytically functional zinc ions. Although penicillinases in Gram-positive bacteria were reported shortly after penicillin was introduced clinically, transmissible β-lactamases that could hydrolyze recently approved cephalosporins, monobactams, and carbapenems later became important in Gram-negative pathogens. Nomenclature is based on one of two major systems. Originally, functional classifications were used, based on substrate and inhibitor profiles. A later scheme classifies β-lactamases according to amino acid sequences, resulting in class A, B, C, and D enzymes. A more recent nomenclature combines the molecular and biochemical classifications into 17 functional groups that describe most β-lactamases. Some of the most problematic enzymes in the clinical community include extended-spectrum β-lactamases (ESBLs) and the serine and metallo-carbapenemases, all of which are at least partially addressed with new β-lactamase inhibitor combinations. New enzyme variants continue to be described, partly because of the ease of obtaining sequence data from whole-genome sequencing studies. Often, these new enzymes are devoid of any phenotypic descriptions, making it more difficult for clinicians and antibiotic researchers to address new challenges that may be posed by unusual β-lactamases.

Rapid demonstration of septic or infectious arthritis due to Gram-negative bacteria

1992 ◽  
Vol 50 (1) ◽  
pp. 686-687
Author(s):  
Jacob S. Hanker ◽  
Paul R. Gross ◽  
Beverly L. Giammara
Keyword(s):  
Chronic Arthritis ◽  
Blood Cultures ◽  
Gram Negative Bacteria ◽  
Infectious Arthritis ◽  
Bacterial Arthritis ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria

Blood cultures are positive in approximately only 50 per cent of the patients with nongonococcal bacterial infectious arthritis and about 20 per cent of those with gonococcal arthritis. But the concept that gram-negative bacteria could be involved even in chronic arthritis is well-supported. Gram stains are more definitive in staphylococcal arthritis caused by gram-positive bacteria than in bacterial arthritis due to gram-negative bacteria. In the latter situation where gram-negative bacilli are the problem, Gram stains are helpful for 50% of the patients; they are only helpful for 25% of the patients, however, where gram-negative gonococci are the problem. In arthritis due to gram-positive Staphylococci. Gramstained smears are positive for 75% of the patients.

Antibacterial activity of magnesium oxide nanoparticles prepared by Calcination method

2019 ◽  
Vol 10 (03) ◽  
Author(s):  
Elaf Ayad Kadhem ◽  
Miaad Hamzah Zghair ◽  
Sarah , Hussam H. Tizkam, Shoeb Alahmad Salih Mahdi ◽  
Hussam H. Tizkam ◽  
Shoeb Alahmad
Keyword(s):  
Antibacterial Activity ◽  
Magnesium Oxide ◽  
Diffusion Method ◽  
Oxide Nanoparticles ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Magnesium Oxide Nanoparticles ◽  
Agar Disc

magnesium oxide nanoparticles (MgO NPs) were prepared by simple wet chemical method using different calcination temperatures. The prepared NPs were characterized by Electrostatic Discharge (ESD), Scanning Electron Microscope (SEM) and X-ray Diffraction (XRD). It demonstrates sharp intensive peak with the increase of crystallinty and increase of the size with varying morphologies with respect to increase of calcination temperature. Antibacterial studies were done on gram negative bacteria (E.coli) and gram positive bacteria (S.aureus) by agar disc diffusion method. The zones of inhibitions were found larger for gram positive bacteria than gram negative bacteria, this mean, antibacterial MgO NPs activity more active on gram positive bacteria than gram negative bacteria because of the structural differences. It was found that antibacterial activity of MgO NPs was found it has directly proportional with their concentration.

BAKTERI PADA KARANG SCLERACTINIA DI KAWASAN PERAIRAN BUNAKEN, MOROTAI DAN RAJA AMPAT

2020 ◽  
Vol 8 (1) ◽  
pp. 122
Author(s):  
Eghbert Eghbert Elvan Eghbert Elvan Ampou ◽  
Iis Iis Triyulianti ◽  
Nuryani Widagti ◽  
Suciadi Catur Nugroho ◽  
Yuli Pancawati
Keyword(s):  
Scleractinian Coral ◽  
Gram Negative Bacteria ◽  
Hard Coral ◽  
Field Sampling ◽  
Bacterial Isolation ◽  
Gram Positive ◽  
Coral Mucus ◽  
Gram Negative ◽  
Gram Positive Bacteria

Research on hard coral (Scleractinian coral) contaminated with bacteria is still not much done, especially in Indonesian waters. This study took samples of coral mucus in 2010 at 3 (three) different locations, namely Bunaken (May); Morotai (September) and Raja Ampat (November), which focused on the analysis of Research on hard coral (Scleractinian coral) contaminated with bacteria is still not much done, especially in Indonesian waters. This study took samples of coral mucus in 2010 at 3 (three) different locations, namely Bunaken (May); Morotai (September) and Raja Ampat (November), which focused on the analysis of gram-positive and gram-negative bacteria. The method used for field sampling is time swim, which is by diving at a depth of 5-10 meters for ± 30 minutes and randomly taking samples of coral mucus using siring or by taking directly on corals (reef branching). Mucus samples were analyzed by bacterial isolation in the laboratory. The result shows that there were differences between gram-positive and gram-negative bacteria in the three research sites and that gram-positive bacteria were higher or dominant. Further research that can identify the bacteria species and explain its relationship to the ecosystem is highly recommended.Keywords: Bacteria, Scleractinian coral, gram-positive and -negative, Bunaken, Morotai, Raja Ampat  AbstrakPenelitian tentang karang keras (Scleractinian coral) yang terkontaminasi bakteri masih belum banyak dilakukan, terutama di perairan Indonesia. Penelitian ini mengambil sampel mucus karang pada tahun 2010 di 3 (tiga) lokasi berbeda, yakni Bunaken (Mei); Morotai (September) dan Raja Ampat (November), yang difokuskan pada analisis bakteri gram postif dan gram negatif. Metode yang digunakan untuk pengambilan sampel di lapangan adalah time swim, yaitu dengan penyelaman pada kedalaman 5-10 meter selama ±30 menit dan mengambil sampel mucus karang secara acak menggunakan siring atau dengan mengambil langsung pada karang (fraksi cabang). Sampel mucus dianalisis dengan cara isolasi bakteri di laboratorium. Hasil analisis menunjukkan bahwa ada perbedaan antara bakteri gram positif dan gram negative di tiga lokasi survei dan bakteri gram positif lebih tinggi atau dominan. Penelitian lebih lanjut yang dapat menentukan jenis bakteri serta menjelaskan hubungannya dengan ekosistem sangat disarankan untuk dilakukan.Kata Kunci : Bakteri, Scleractinian coral, gram positif dan negatif, Bunaken, Morotai, Raja Ampat

scholarly journals N-Doped Carbon Quantum Dots as Fluorescent Bioimaging Agents

Crystals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 789
Author(s):  
Shih-Fu Ou ◽  
Ya-Yun Zheng ◽  
Sin-Jen Lee ◽  
Shyi-Tien Chen ◽  
Chien-Hui Wu ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Carbon Nanomaterials ◽  
Graphene Quantum Dots ◽  
Carbon Quantum Dots ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Fluorescence Characteristics ◽  
And Staphylococcus Aureus

Graphene quantum dots, carbon nanomaterials with excellent fluorescence characteristics, are advantageous for use in biological systems owing to their small size, non-toxicity, and biocompatibility. We used the hydrothermal method to prepare functional N-doped carbon quantum dots (N-CQDs) from 1,3,6-trinitropyrene and analyzed their ability to fluorescently stain various bacteria. Our results showed that N-CQDs stain the cell septa and membrane of the Gram-negative bacteria Escherichia coli, Salmonellaenteritidis, and Vibrio parahaemolyticus and the Gram-positive bacteria Bacillus subtilis, Listeria monocytogenes, and Staphylococcus aureus. The optimal concentration of N-CQDs was approximately 500 ppm for Gram-negative bacteria and 1000 ppm for Gram-positive bacteria, and the exposure times varied with bacteria. N-Doped carbon quantum dots have better light stability and higher photobleaching resistance than the commercially available FM4-64. When excited at two different wavelengths, N-CQDs can emit light of both red and green wavelengths, making them ideal for bioimaging. They can also specifically stain Gram-positive and Gram-negative bacterial cell membranes. We developed an inexpensive, relatively easy, and bio-friendly method to synthesize an N-CQD composite. Additionally, they can serve as a universal bacterial membrane-staining dye, with better photobleaching resistance than commercial dyes.

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 Pyelonephritis in Pediatric Uropathic Patients: Differences from Community-Acquired Ones and Therapeutic Protocol Considerations. A 10-Year Single-Center Retrospective Study

Children ◽  
2021 ◽  
Vol 8 (6) ◽  
pp. 436
Author(s):  
Giovanni Parente ◽  
Tommaso Gargano ◽  
Stefania Pavia ◽  
Chiara Cordola ◽  
Marzia Vastano ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Retrospective Study ◽  
Success Rate ◽  
Pediatric Population ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Significant Difference ◽  
Klebsiella Spp

Pyelonephritis (PN) represents an important cause of morbidity in the pediatric population, especially in uropathic patients. The aim of the study is to demonstrate differences between PNs of uropathic patients and PNs acquired in community in terms of uropathogens involved and antibiotic sensitivity; moreover, to identify a proper empiric therapeutic strategy. A retrospective study was conducted on antibiograms on urine cultures from PNs in vesicoureteral reflux (VUR) patients admitted to pediatric surgery department and from PNs in not VUR patients admitted to Pediatric Emergency Unit between 2010 and 2020. We recorded 58 PNs in 33 patients affected by VUR and 112 PNs in the not VUR group. The mean age of not VUR patients at the PN episode was 1.3 ± 2.6 years (range: 20 days of life–3 years), and almost all the urine cultures, 111 (99.1%), isolated Gram-negative bacteria and rarely, 1 (0.9%), Gram-positive bacteria. The Gram-negative uropathogens isolated were Escherichia coli (97%), Proteus mirabilis (2%), and Klebsiella spp. (1%). The only Gram-positive bacteria isolated was an Enterococcus faecalis. As regards the antibiograms, 96% of not VUR PNs responded to beta-lactams, 99% to aminoglycosides, and 80% to sulfonamides. For the VUR group, mean age was 3.0 years ± 3.0 years (range: 9 days of life–11 years) and mean number of episodes per patient was 2.0 ± 1.0 (range: 1–5); 83% of PNs were by Gram-negatives bacteria vs. 17% by Gram-positive: the most important Gram-negative bacteria were Pseudomonas aeruginosa (44%), Escherichia coli (27%), and Klebsiella spp. (12%), while Enterococcus spp. determined 90% of Gram-positive UTIs. Regimen ampicillin/ceftazidime (success rate: 72.0%) was compared to ampicillin/amikacin (success rate of 83.0%): no statistically significant difference was found (p = 0.09). The pathogens of PNs in uropathic patients are different from those of community-acquired PNs, and clinicians should be aware of their peculiar antibiotic susceptibility. An empiric therapy based on the association ampicillin + ceftazidime is therefore suggested.

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