Disease relevance of Cephamycin

• Genes for a beta-lactamase, a penicillin-binding protein and a transmembrane protein are clustered with the cephamycin biosynthetic genes in Nocardia lactamdurans [1].
• The DNA-binding capability of a key secondary metabolite regulatory element (CcaR) in the Streptomyces clavuligerus cephamycin C pathway was investigated by gel mobility retardation and DNase I footprinting analysis [2].
• The class B, metallo-beta-lactamase genes ccrA (carbapenem- and cephamycin resistance) from three Bacteroides fragilis isolates--QMCN3, QMCN4, and TAL3636--were cloned and expressed in Escherichia coli [3].
• Force field design and molecular dynamics simulations of the carbapenem- and cephamycin-resistant dinuclear zinc metallo-beta-lactamase from Bacteroides fragilis and its complex with a biphenyl tetrazole inhibitor [4].
• Delta-1-piperideine-6-carboxylate dehydrogenase, a new enzyme that forms alpha-aminoadipate in Streptomyces clavuligerus and other cephamycin C-producing actinomycetes [5].

High impact information on Cephamycin

• Eight PBPs were found in the membranes of N. lactamdurans, none of which bind cephamycin C, which explains the resistance of this strain to its own antibiotic [1].
• These results indicate that two different proteins bind specifically to the ARE sequence and modulate clavulanic acid and cephamycin C [corrected] biosynthesis by its action on ccaR gene expression [6].
• The corresponding isogenic strain containing ccaR:gfp in the chromosome produced cephamycin C at levels similar to those of wild-type S. clavuligerus [2].
• Cephamycin resistance in clinical isolates and laboratory-derived strains of Escherichia coli, Nova Scotia, Canada [7].
• Expression of ccaR, encoding the positive activator of cephamycin C and clavulanic acid production in Streptomyces clavuligerus, is dependent on bldG [8].

Chemical compound and disease context of Cephamycin

• Cefoxitin is a beta-lactam antibiotic derived from cephamycin C, a naturally occurring substance produced by Streptomyces lactamdurans [9].
• L-lysine epsilon-aminotransferase involved in cephamycin C synthesis in Streptomyces lactamdurans [10].
• New cephamycin antibiotic, CS-1170: binding affinity to penicillin-binding proteins and inhibition of peptidoglycan cross-linking reactions in Escherichia coli [11].
• The S. griseus pcbC gene was not expressed in Streptomyces lividans but was expressed in Streptomyces clavuligerus and complemented a mutation, nce2, that impaired isopenicillin N synthase and cephamycin biosynthesis [12].
• Increased susceptibility to cephamycin-type antibiotics of methicillin-resistant Staphylococcus aureus defective in penicillin-binding protein 2 [13].

Biological context of Cephamycin

• Pharmacokinetics of new broad-spectrum cephamycin, YM09330, parenterally administered to various experimental animals [14].
• Cefmetazole is a cephamycin antibiotic which is resistant to hydrolysis by various beta-lactamases [15].
• These two promoters are arranged in a bidirectional transcription initiation region located in the center of the cephamycin gene cluster [16].
• The nine genes of the Nocardia lactamdurans cephamycin cluster are transcribed into large mRNAs from three promoters, two of them located in a bidirectional promoter region [17].
• These include genes encoding an apparent penicillin binding protein and a transport or efflux protein, as well as the CmcI and CmcJ proteins, which catalyze late reactions in the cephamycin biosynthetic pathway [18].

Anatomical context of Cephamycin

• A 7-alpha-methoxycephalosporin containing a carbamoyloxymethyl substituent at C-3 (cephamycin C) has been isolated from the extracellular fluid of an aqueous suspension of Streptomyces clavuligerus shaken in the presence of 18O2 [19].
• Effects of MT-141, a new cephamycin antibiotic, on acute urinary tract infections [20].

Associations of Cephamycin with other chemical compounds

• Cefotetan, a new cephamycin: comparison of in vitro antimicrobial activity with other cephems, beta-lactamase stability, and preliminary recommendations for disk diffusion testing [21].
• Intracellular levels of the P7 protein (a component of the methoxylation system involved in cephamycin biosynthesis) were increased by diaminopropane, as shown by immunoblotting studies [22].
• We evaluated the performances of three methods for detection of low-level methicillin resistance: the disk diffusion method using the cephamycin antibiotics cefoxitin and moxalactam, the Vitek 2 system (bioMérieux), and the MRSA-screen test (Denka) [23].
• Cefoxitin (mefoxin), a new semisynthetic cephamycin antibiotic, resistant to degradation by beta-lactamase enzymes produced by bacteria [24].
• The pharmacokinetics of cefoxitin, a new cephamycin antibiotic, were studied in six patients who were undergoing total hip replacement, and who were given cefoxitin to provide prophylactic cover at the time of operation [25].

Gene context of Cephamycin

• If an investigational AmpC beta-lactamase inhibitor was made available for diagnostic testing, it could be useful in combination with a suitable cephamycin to confirm AmpC production [26].
• The majority of cephamycin resistant E. coli strains in Toronto have attenuator and/or promotor mutations upstream of the chromosomal ampC gene [27].
• The positive activator of cephamycin C and clavulanic acid production in Streptomyces clavuligerus is mistranslated in a bldA mutant [28].
• Cephamycin inactivation due to enzymatic hydrolysis by beta-lactamase from Bacteroides fragilis [29].
• In vivo selection of a cephamycin-resistant, porin-deficient mutant of Klebsiella pneumoniae producing a TEM-3 beta-lactamase [30].

Analytical, diagnostic and therapeutic context of Cephamycin

• Time-lapsed confocal microscopy of the S. clavuligerus LH369 strain revealed the temporal and spatial characteristics of lat gene expression and demonstrated that physiological development of S. clavuligerus colonies leading to cephamycin C biosynthesis is limited to the substrate mycelia [31].
• The pharmacokinetics of cefmetazole, a new cephamycin antibiotic, were examined after a 1-h intravenous drip infusion of 1 g to 5 healthy volunteers with normal renal function and 16 patients with impaired renal function [32].
• As part of a search for transcriptional regulatory genes, sequence analysis of several previously unsequenced gaps in the cephamycin biosynthetic cluster has revealed the presence in Streptomyces clavuligerus of seven genes not previously described [18].
• The nine biosynthesis genes of the Nocardia lactamdurans cephamycin cluster are expressed as three different mRNAs initiating at promoters latp, cefDp, and pcbABp, as shown by low-resolution S1 nuclease protection assays and Northern blotting analysis [17].
• Amplification of the ccaR promoter region lacking its coding sequence in a high-copy-number plasmid in S. clavuligerus ATCC 27064 resulted in a reduced production of cephamycin C and clavulanic acid, by 12 to 20% and 40 to 60%, respectively, due to titration of the CcaR regulator [33].

References