P-lactam resistance

P-Lactamases are enzymes that hydrolyze the P-lactam ring of P-lactamantibiotics (penicillins, cephalosporins, monobactams and carbapenems). They are the most common cause of P-lactam resistance. Most enzymes use a serine residue in the active site that attacks the P-lactam-amid carbonyl group. The covalently formed acylester is then hydrolyzed to reactivate the P-lacta-mase and liberates the inactivated antibiotic. Metallo P-lactamases use Zn(II) bound water for hydrolysis of the P-lactam bond. P-Lactamases constitute a heterogeneous group of enzymes with differences in molecular structures, in substrate preferences and in the genetic localizations of the encoding gene (Table 1). 

An additional mechanism of antibiotic resistance involves an alteration of PBPs. Resistant bacteria, usually gram-positive organisms, produce PBPs with low affinity for p-lactam antibiotics. The development of mutations of bacterial PBPs is involved in the mechanism for p-lactam resistance in Streptococcus pneumoniae. Enterococcus faecium, and methicillin-resistant S. aureus (MRS A). 

Pseudomonas aemffnosa, p lactam resistance due to chromosomal p-lactamase derepression in Entercdmaer cloacae or plasmid-encoded TEM P-lacramase in Esc/ietichia coti, and tetracycline eliHux in E. coii, have no effect on the MIC of cationic peptides (66). Furthermore, they themselves do not tend to select resistant mutants, although some bacteria, such as Burldiolieria cepacia tend to be naturally resistant. 

Overall, the shotgun-proteomics findings were consistent with the minimal inhibitory concentration (MIC) determination results because all 20 A. baumannii clinical isolates were foimd resistant to carbapenem, monobactam, cephalosporin, and to a combination treatment of penicillin and P-lactamase inhibitors. The results obtained demonstrate that by augmenting the custom DB with strain-specific unique peptide sequences, it is possible to obtain simultaneously both strain-level identification of. baumannii clinical isolates and their antibiotic resistance mechanism information within 5-6 h. Therefore, the approach developed by Chang et al (2013) could be used for a rapid, sensitive, and specific detection of P-lactam-resistant strains of. baumannii. 

Chang CJ, Lin JH, Chang KC, et al. Diagnosis of p-lactam resistance in Acinetobacter baumannii using shotgun proteomics and LC-nano-electrospray ionization ion trap mass spectrometry. Anal Chem. 2013 85 2802-8. doi 10.1021/ac303326a. 

Biphenomycin B 11 is a 15-membered cyclic tripeptide isolated from the culture broths of Streptomyces filipinensis and S. griseorubuginosus. This compound displayed potent activity against Gram-positive, p-lactam-resistant bacteria, such as Streptococcus aureus. Enterococcus faecalis, or Streptococcus sp. The enantioselective total syntheses of biphenomycin B 11 using an asymmetric phase-transfer alkylation were reported by two groups. 

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