ChemInform Abstract: Synthesis of Phenylacetyl-L-cysteinyl-D-valine Disulfide. A Biosynthetic Precursor of Penicillin G.

ChemInform ◽  
1989 ◽  
Vol 20 (24) ◽  
Author(s):  
J. M. LUENGO ◽  
M. T. ALEMANY ◽  
M. J. ARIN ◽  
M. T. DIEZ ◽  
F. SALTO
Keyword(s):  
Penicillin G ◽  
Biosynthetic Precursor

Cytochemical Studies of Cell Wall Biosynthesis in Staphylococcus Aureus

1972 ◽  
Vol 30 ◽  
pp. 328-329
Author(s):  
Masaatsu Koike ◽  
Koichi Nakashima ◽  
Kyoko Iida
Keyword(s):  
Staphylococcus Aureus ◽  
Periodate Oxidation ◽  
Early Time ◽  
The Other ◽  
Penicillin G ◽  
Cell Wall Biosynthesis ◽  
Septal Wall ◽  
Peptidoglycan Biosynthesis ◽  
Gram Positive Bacteria ◽  
Cross Linkage

Penicillin exerts the activity to inhibit the peptide cross linkage between each polysaccharide backbone at the final stage of wall-peptidoglycan biosynthesis of bacteria. Morphologically, alterations of the septal wall and mesosome in gram-positive bacteria, which were occurred in early time after treatment with penicillin, have been observed. In this experiment, these alterations were cytochemically investigated by means of silver-methenamine staining after periodate oxidation, which is applied for detection of localization of wall mucopolysaccharide.Staphylococcus aureus strain 209P treated with 100 u/ml of penicillin G was divided into two aliquotes. One was fixed by Kellenberger-Ryter's OSO4 fixative at 30, 60 and 120 min after addition of the antibiotic, dehydrated through alcohol series, and embedded in Epon 812 (Specimen A). The other was fixed by 21 glutaraldehyde, dehydrated through glycolmethacrylate series and embedded in glycolmethacrylate mixture, according to Bernhard's method (Specimen B).

Synthesis and Reactivity of Precolibactin 886

2019 ◽  
Author(s):  
Seth Herzon ◽  
Alan R. Healy ◽  
kevin wernke ◽  
Chung Sub Kim ◽  
Nicholas Lees ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gene Cluster ◽  
Amino Alcohol ◽  
Biomimetic Synthesis ◽  
Cross Linking ◽  
E Coli ◽  
Hplc Purification ◽  
Structural Assignment ◽  
Biosynthetic Precursor ◽  
Double Oxidation

<div>The clb gene cluster encodes the biosynthesis of metabolites known as precolibactins and colibactins. The clb pathway is found in gut commensal E. coli, and clb metabolites are thought to initiate colorectal cancer via DNA cross-linking. Precolibactin 886 (1) is one of the most complex isolated clb metabolites; it contains a 15-atom macrocycle and an unusual 5-hydroxy-3-oxazoline ring. Here we report confirmation of the structural assignment via a biomimetic synthesis of precolibactin 886 (1) proceeding through the amino alcohol 9. Double oxidation of 9 afforded the unstable α-ketoimine 2 which underwent macrocyclization to precolibactin 886 (1) upon HPLC purification (3% from 9). Studies of the putative precolibactin 886 (1) biosynthetic precursor 2, the model α-ketoimine 25, and the α-dicarbonyl 26 revealed that these compounds are susceptible to nucleophilic rupture of the C36–C37 bond. Moreover, cleavage of 2 produces other known clb metabolites or biosynthetic intermediates. This unexpected reactivity explains the difficulties in isolating full clb metabolites and accounts for the structure of a recently identified colibactin–adenine adduct. The colibactin peptidase ClbP deacylates synthetic precolibactin 886 (1) to form a non-genotoxic pyridone, suggesting precolibactin 886 (1) lies off-path of the major biosynthetic route.</div>

Pharmacokinetic Drug-drug Interaction of Antibiotics Used in Sepsis Care in China

2020 ◽  
Vol 21 ◽  
Author(s):  
Xuan Yu ◽  
Zixuan Chu ◽  
Jian Li ◽  
Rongrong He ◽  
Yaya Wang ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Drug Interactions ◽  
Penicillin G ◽  
Literature Mining ◽  
Human Pharmacokinetics ◽  
P450 Enzyme ◽  
Drug Drug Interaction ◽  
Pharmacokinetic Drug ◽  
Sepsis Care

Background: Many antibiotics have a high potential for having an interaction with drugs, as perpetrator and/or victim, in critically ill patients, and particularly in sepsis patients. Methods: The aim of this review is to summarize the pharmacokinetic drug-drug interaction (DDI) of 45 antibiotics commonly used in sepsis care in China. Literature mining was conducted to obtain human pharmacokinetics/dispositions of the antibiotics, their interactions with drug metabolizing enzymes or transporters, and their associated clinical drug interactions. Potential DDI is indicated by a DDI index > 0.1 for inhibition or a treated-cell/untreated-cell ratio of enzyme activity being > 2 for induction. Results: The literature-mined information on human pharmacokinetics of the identified antibiotics and their potential drug interactions is summarized. Conclusion: Antibiotic-perpetrated drug interactions, involving P450 enzyme inhibition, have been reported for four lipophilic antibacterials (ciprofloxacin, erythromycin, trimethoprim, and trimethoprim-sulfamethoxazole) and three lipophilic antifungals (fluconazole, itraconazole, and voriconazole). In addition, seven hydrophilic antibacterials (ceftriaxone, cefamandole, piperacillin, penicillin G, amikacin, metronidazole, and linezolid) inhibit drug transporters in vitro. Despite no reported clinical PK drug interactions with the transporters, caution is advised in the use of these antibacterials. Eight hydrophilic antibacterials (all β-lactams; meropenem, cefotaxime, cefazolin, piperacillin, ticarcillin, penicillin G, ampicillin, and flucloxacillin), are potential victims of drug interactions due to transporter inhibition. Rifampin is reported to perpetrate drug interactions by inducing CYP3A or inhibiting OATP1B; it is also reported to be a victim of drug interactions, due to the dual inhibition of CYP3A4 and OATP1B by indinavir. In addition, three antifungals (caspofungin, itraconazole, and voriconazole) are reported to be victims of drug interactions because of P450 enzyme induction. Reports for other antibiotics acting as victims in drug interactions are scarce.

scholarly journals Corynebacterium jeikeium native valve infective endocarditis case report: a confirmed microbiological and pathological diagnosis from heart valvular tissue

2020 ◽  
Author(s):  
Wentzel Bruce Dowling ◽  
Johan Koen
Keyword(s):  
Infective Endocarditis ◽  
Aortic Valve ◽  
Penicillin G ◽  
Peripheral Vascular ◽  
Native Valve ◽  
Valve Tissue ◽  
Case Summary ◽  
Duke Criteria ◽  
G Prior ◽  
Initial Blood

Abstract Background The Modified Duke criteria is an important structured schematic for the diagnosis of infective endocarditis (IE). Corynebacterium jeikeium is a rare cause of IE that is often resistant to standard IE anti-microbials. We present a case of C. jeikeium IE, fulfilling the Modified Duke pathological criteria. Case summary A 50-year-old male presented with left leg peripheral vascular disease with septic changes requiring amputation. Routine echocardiography post-amputation demonstrated severe aortic valve regurgitation with vegetations that required valve replacement. Two initial blood cultures from a single venepuncture showed Streptococcus mitis which was treated with penicillin G prior to surgery. Subsequent aortic valve tissue cultured C. jeikeium with suggestive IE histological valvular changes and was successfully treated on a prolonged course of vancomycin. Discussion This is the first C. jeikeium IE case diagnosed on heart valvular tissue culture and highlights the importance for the fulfilment of the Modified Duke criteria in diagnosing left-sided IE. Mixed infection IE is rare, and this case possibly represents an unmasking of resistant C. jeikeium IE following initial treatment of penicillin G.

scholarly journals Structure-Properties Correlation of Cross-Linked Penicillin G Acylase Crystals

Crystals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 451
Author(s):  
Marta Kubiak ◽  
Janine Mayer ◽  
Ingo Kampen ◽  
Carsten Schilde ◽  
Rebekka Biedendieck
Keyword(s):  
Mechanical Stability ◽  
Structural Characteristics ◽  
Penicillin G ◽  
Bacillus Species ◽  
Diffusion Limitations ◽  
Small Water ◽  
Long Term Stability ◽  
Atomic Force ◽  
First Time

In biocatalytic processes, the use of free enzymes is often limited due to the lack of long-term stability and reusability. To counteract this, enzymes can be crystallized and then immobilized, generating cross-linked enzyme crystals (CLECs). As mechanical stability and activity of CLECs are crucial, different penicillin G acylases (PGAs) from Gram-positive organisms have proven to be promising candidates for industrial production of new semisynthetic antibiotics, which can be crystallized and cross-linked to characterize the resulting CLECs regarding their mechanical and catalytic properties. The greatest hardness and Young’s modulus determined by indentation with an atomic force microscope were observed for CLECs of Bacillus species FJAT-PGA CLECs (26 MPa/1450 MPa), followed by BmPGA (Priestia megaterium PGA, 23 MPa/1170 MPa) and BtPGA CLECs (Bacillus thermotolerans PGA, 11 MPa/614 MPa). In addition, FJAT- and BtPGA CLECs showed up to 20-fold higher volumetric activities compared to BmPGA CLECs. Correlation to structural characteristics indicated that a high solvent content and low number of cross-linking residues might lead to reduced stability. Furthermore, activity seems to be restricted by small water channels due to severe diffusion limitations. To the best of our knowledge, we show for the first time in this study that the entire process chain for the characterization of diverse industrially relevant enzymes can be performed at the microliter scale to discover the most important relationships and limitations.

scholarly journals 270. Clinical Outcomes of Ceftriaxone versus Penicillin G for Complicated Viridans Group Streptococci Bacteremia

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S137-S137
Author(s):  
Stephanie Wo ◽  
Yanina Dubrovskaya ◽  
Justin Siegfried ◽  
John Papadopoulos ◽  
Shin-Pung Jen
Keyword(s):  
Clinical Outcomes ◽  
Hospital Readmission ◽  
Protective Factor ◽  
Primary Outcome ◽  
Bloodstream Infections ◽  
Penicillin G ◽  
Eligibility Criteria ◽  
Extended Spectrum Beta Lactamase ◽  
Increased Risk ◽  
Viridans Group Streptococci

Abstract Background Viridans group streptococci (VGS) is an infrequent yet significant cause of bloodstream infections, and complicated cases may require prolonged antibiotic therapy. Ceftriaxone (CTX) and penicillin G (PCN G) are both considered first line options for VGS infections, but comparisons between these agents are limited. We evaluated the clinical outcomes amongst patients treated with CTX and PCN G for complicated VGS bacteremia. Methods This was a single-center, retrospective study of adult patients with ≥1 positive VGS blood culture who were treated with either CTX or PCN G/ampicillin (both included in PCN G arm) between January 2013 and June 2019. The primary outcome was a composite of safety endpoints, including hospital readmission due to VGS or an adverse event (AE) from therapy, Clostridioides difficile infections, treatment modification or discontinuation due to an antibiotic-related AE, and development of extended-spectrum beta lactamase resistance. Secondary outcomes included the individual safety endpoints, VGS bacteremia recurrence, hospital readmission, and all-cause mortality. Results Of 328 patients screened for inclusion, 94 patients met eligibility criteria (CTX n= 64, PCN G n=34). Median age was 68 years (IQR 56–81) and 68% were male. Study patients did not present with critical illness, as reflected by a median Pitt bacteremia score of 0 in the CTX and 1 in the PCN G arms, P=0.764. Streptococcus mitis was the most common VGS isolate and infective endocarditis (IE) was the predominant source of infection. CTX was not significantly associated with increased risk of the primary outcome (14% vs. 27%; P= 0.139). The driver of the composite outcome was hospital readmission due to VGS bacteremia or therapy complications. Results were similar in the subgroup of patients with IE (12.5% vs. 23.5%). No secondary endpoints differed significantly between groups. On multivariate analysis, source removal was a protective factor of the primary outcome (OR 0.1; 95% CI 0.020–0.6771; P= 0.017). Conclusion Despite potential safety concerns with the prolonged use of CTX in complicated VGS bacteremia, this study did not demonstrate a higher rate of treatment failure, adverse events, or resistance. These findings warrant further exploration. Disclosures All Authors: No reported disclosures

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