Search

We have studied the mechanism by which [beta]-Iactam challenge leads to [beta]-lactamase induction in Aeromonas hydrophila through transposon-insertion mutagenesis. Disruption of the DD-carboxypeptidases/endopeptidases, penicillin-binding protein 4 or BIrY leads to elevated monomer-disaccharide-pentapeptide levels in A. hydrophila peptidoglycan and concomitant overproduction of [beta]-Iactamase through activation of the BIrAB two-component regulatory system. During [beta]-lactam challenge, monomer-disaccharide-pentapeptide levels increase proportionately with [beta]-lactamase production and [beta]-lactamase induction is inhibited by vancomycin, which binds muro-pentapeptides. Taken together, these data strongly suggest that the Aeromonas spp. [beta]-lactamase regulatory sensor kinase, BIrB, responds to the concentration of monomerdisaccharide-pentapeptide in peptidoglycan. DOI 10.1099/mic.0.035220-0

Background. Intrapartum antibiotic prophylaxis against group B Streptococcus (GBS) has reduced the occurrence of serious bacterial infections (SBI) in young infants caused by GBS. Recommendations for initial antibiotic therapy for the febrile infant 1 to 90 days old were developed when infections with GBS were common and antibiotic resistance was rare. Objective. To document the pathogens responsible for SBI in recent years in febrile infants 1 to 90 days old and the antibiotic susceptibility of these organisms. Methods. The results of bacterial cultures from infants 1 to 90 days old evaluated for fever at Primary Children's Medical Center in Salt Lake City, Utah, between July 1999 and April 2002 were analyzed. Antibiotic susceptibility profiles were collected and patient records were reviewed to determine if initial antibiotic therapy was changed following the identification of the organism. Results. Of 1298 febrile infants enrolled from the Primary Children's Medical Center emergency department, 105 (8%) had SBI. The mean age of the infants with SBI was 39 days (range 2-82 days) and 2 (2%) were Of the 105 pathogens, 56 (53%) were resistant to ampicillin. Of the pathogens causing meningitis, UTI, and bacteremia, 78%, 53%, and 50%, respectively, were resistant to ampicillin. Antibiotic therapy was changed in 54% of cases of SBI following identification of the organism. Conclusions. In Utah, ampicillin-resistant Gram-negative bacteria are the most common cause of SBI in febrile infants, ABBREVIATIONS. GBS, group B Streptococcus; SBI, serious bacterial infection; UTI, urinary tract infection; ESBL, extended spectrum [beta]-lactamases; ampC, ampC [beta]-lactamases; PCMC, Primary Children's Medical Center; ED, emergency department; CSF, cerebrospinal [...]

Research has been conducted on the 4-alkyl-4-carboxy-2-azetidinones. The asymmetric synthesis of these compounds derived from amino acids has been carried out and the results indicate that the beta-lactam ring construction has been produced via the N (super)alpha -chloroacetyl derivative's intramolecular cyclization.

Research has been conducted on the fused bicyclic and tricyclic beta-lactam derivatives. The construction of these derivatives has been carried out and the results indicate that the cyclization has been followed by the beta-lactam ring cleavage and has lead to the functionalized proline derivative formation.

Research has been conducted on the differently substituted 5-dethia-5-oxacephams. The chiroptical properties of these compounds and their molecular structures have been examined and the correlation between the oxacephams' stereochemistry and circular dichroism band signs has been established.

While some trends in antimicrobial resistance rates are universal, others appear to be unique for specific regions. In Taiwan, the strikingly high prevalence of resistance to macrolides and streptogramin in [...]

Research demonstrates that in Escherichia coli, the bacteriolytic beta-lactam cefsulodin induced cell lysis occurs at division sites where zonal synthesis of peptidoglycan or murein is activated, leading to septum formation.

Research has been conducted on the N-acyl-4-acyloxy-beta-lactams. The conversion of these compounds into 1,3-oxazin-6-ones has been investigated via the ab initio and density functional theories and the results indicate the involvement of the pseudopericyclic reactions in this process.

Research has been conducted on the beta-hydroxy-alpha-amino acids, useful building blocks for the beta-lactam synthesis. The isolation of ustiloxins from the water extracts of false smut balls on the rice plant panicles caused by a fungus has been carried out and the results of their synthesis are reported.

Research has been conducted on the spiro beta-lactams. The use of the molecular modeling calculations in investigating these beta-lactams is discussed and the results suggest that these systems could adopt a beta-turn secondary structure in solution.

Research has been conducted on the optically pure azetidine-2,3-diones. The metal-mediated carbonyl allylation, propargylation and allenylation of these diones have been investigated in anhydrous and aqueous media and the results indicate that different metal promoters have exhibited varied regioselectivities on product formation during the allenylation/propargylation keto-beta-lactam reactions.

Research demonstrates that the antibiotic pressure uniquely changes the structure of the beta-lactam antibiotic susceptible regulatory sequence of the Staphylococcus sciuri mecA homologue, converting it to an antibiotic resistance determinant that can express the resistant phenotype in the genetic background of S. aureus.

Research has been conducted on the chiral nonracemic bicyclic beta-lactams. The straightforward synthesis of these beta-lactams has been performed via the Baylis-Hillman reaction of 4-oxoazetidine-2-carbaldehydes with free radicals and the results are presented.

Results demonstrate that beta-lactam synthetase of Streptomyces clavuligerus binds substrates in an orderly fashion , with ATP binding first. Kinetic data reveal that the alakaline amino acids should be in the ionized form for optimal activity of the enzyme.

The apical H+-coupled peptide transporter (PEPT1) and basolateral peptide transporter in human intestinal Caco-2 cells were functionally compared by the characterization of (14C)glycylsarcosine transport. Results indicated that a single facilitative peptide transporter is expressed at the basolateral membranes of Caco-2 cells and that PEPT1 and the basolateral peptide transporter cooperate in the efficient transepithelial transport of small peptides and peptide-like drugs.

The temperature sensitivity of the lysis reaction to beta-lactam antibiotic observed in Escherichia coli deprived of amino acids is not due to the heat shock response as reported by previous studies. Mutation studies revealed that E. coli strains that lack the heat shock response gene exhibited similar temperature sensitivity to beta-lactam induced lysis as wild-type E. coli. The temperature sensitivity of the lysis response may be due to direct thermoinactivation of a peptidoglycan hydrolase.

The LLC-PK1 cells were established to stably express rat PEPT2 and the recognition of beta-lactam antibiotics was compared using rat PEPT2- and PEPT1-expressing transfectants. PEPT1 was confirmed as the low-affinity type transporter in the kidney, while PEPT2 was established as the high-affinity type transporter. The comparison of the apparent inhibition constant values for cephalexin and cefadroxil or for ampicillin and amoxicillin revealed that amoxicillin and cefradoxil had higher affinities for PEPT1 and PEPT2.

Molecular genetic analysis of group 1 mutants of the carbapenem antibiotic-producing Erwinia carotovora GS101 involves the isolation of a complementary cosmid cWU142. Sequence analysis of a cWU142 subclone reveals that the carR gene codes for a homologue of the Vibrio fischeri LuxR protein. The carR gene serves as a hot spot target for a Tn5 element transposition, leading to the formation of carR mutants at a high frequency. Genes that code for several metabolic functions such a plasmid conjugation, bioluminescence and cell division are transcriptionally induced by the carR protein, which depends on N-acyl homo-serine lactones for its function.

Inhibition of the beta-lactam-induced lysis of amino acid-deprived bacteria upon relaxation of stringent response reveals the dependence of this lysis on phospholipid synthesis. Two stages, the priming stage and the beta-lactam-independent lysis induction stage, involve in the lysis process during amino acid deprivation. Phospholipid synthesis is essential for both the stages. Inhibition of phospholipid synthesis leads to inhibition of peptidoglycan synthesis and the penicillin tolerance associated with the stringent response.

Research has been conducted on the Mannich reaction involving enolizable imine compounds. The use of these imines in converting the initial carbonyl substrate or azomethine reagent into a more reactive derivative is described.

Results indicate that the beta-lactam biosynthesis genes pcbAB and pcbC of the marine fungus are expressed in the late growth phase of Kallichroma tethys. Complementation analysis suggest that pcbAB is functional and may produce an active beta-lactam antibiotic.

The blanket resistance of methicillin-resistant Staphylococcus aureus to all [Beta]-lactam antibiotics--which had such a devastating impact on chemotherapy of staphylococcal infections--is related to the properties of the key component of this resistance mechanism: the 'acquired' penicillin-binding protein (PBP)-2A, which has unusual low affinity for all [Beta]-lactam antibiotics. Until now, the accepted model of resistance implied that in the presence of [Beta]-lactam antibiotics in the surrounding medium, PBP2A must take over the biosynthesis of staphylococcal cell wall from the four native staphylococcal PBPs because the latter become rapidly acylated and inactivated at even low concentrations of the antibiotic. However, recent observations indicate that this model requires revision. Inactivation of the transglycosylase domain, but not the transpeptidase domain, of PBP2 of S. aureus prevents expression of [Beta]-lactam resistance, despite the presence of the low-affinity PBP2A. The observations suggest that cell-wall synthesis in the presence of [Beta]-lactam antibiotics requires the cooperative functioning of the transglycosylase domain of the native staphylococcal PBP2 and the transpeptidase domain of the PBP2A, a protein imported by S. aureus from an extra species source.

Research has been conducted on the beta-lactams. The copper-catalyzed asymmetric coupling of alkynes with nitrones which forms beta-lactams has been investigated and the details are reported.