Lactam Resistance (lactam + resistance)

Distribution by Scientific Domains


Selected Abstracts


Penicillin-binding proteins and ,-lactam resistance

FEMS MICROBIOLOGY REVIEWS, Issue 2 2008
André Zapun
Abstract A number of ways and means have evolved to provide resistance to eubacteria challenged by ,-lactams. This review is focused on pathogens that resist by expressing low-affinity targets for these antibiotics, the penicillin-binding proteins (PBPs). Even within this narrow focus, a great variety of strategies have been uncovered such as the acquisition of an additional low-affinity PBP, the overexpression of an endogenous low-affinity PBP, the alteration of endogenous PBPs by point mutations or homologous recombination or a combination of the above. [source]


The ,-lactam-sensitive d,d -carboxypeptidase activity of Pbp4 controls the l,d and d,d transpeptidation pathways in Corynebacterium jeikeium

MOLECULAR MICROBIOLOGY, Issue 3 2009
Marie Lavollay
Summary Corynebacterium jeikeium is an emerging nosocomial pathogen responsible for vascular catheters infections, prosthetic endocarditis and septicemia. The treatment of C. jeikeium infections is complicated by the multiresistance of clinical isolates to antibiotics, in particular to ,-lactams, the most broadly used class of antibiotics. To gain insight into the mechanism of ,-lactam resistance, we have determined the structure of the peptidoglycan and shown that C. jeikeium has the dual capacity to catalyse formation of cross-links generated by transpeptidases of the d,d and l,d specificities. Two ampicillin-insensitive cross-linking enzymes were identified, LdtCjk1, a member of the active site cysteine l,d -transpeptidase family, and Pbp2c, a low-affinity class B penicillin-binding protein (PBP). In the absence of ,-lactam, the PBPs and the l,d -transpeptidase contributed to the formation of 62% and 38% of the cross-links respectively. Although LdtCjk1 and Pbp2C were not inhibited by ampicillin, the participation of the l,d -transpeptidase to peptidoglycan cross-linking decreased in the presence of the drug. The specificity of LdtCjk1 for acyl donors containing a tetrapeptide stem accounts for this effect of ampicillin since the essential substrate of LdtCjk1 was produced by an ampicillin-sensitive d,d -carboxypeptidase (Pbp4Cjk). Acquisition and mutational alterations of pbp2C accounted for high-level ,-lactam resistance in C. jeikeium. [source]


Prevalence of AmpC over-expression in bloodstream isolates of Pseudomonas aeruginosa

CLINICAL MICROBIOLOGY AND INFECTION, Issue 4 2007
V. H. Tam
Abstract This study examined the contribution of AmpC over-expression to ,-lactam resistance in clinical isolates of Pseudomonas aeruginosa obtained from a hospital in Houston, TX, USA. Seventy-six non-repeat bloodstream isolates obtained during 2003 were screened for ceftazidime resistance in the presence and absence of clavulanic acid 4 mg/L. AmpC was identified by isoelectric focusing (with and without cloxacillin inhibition); stable derepression was ascertained phenotypically by a spectrophotometric assay (with and without preceding induction by imipenem) using nitrocefin as the substrate, and was confirmed subsequently by quantitative RT-PCR of the ampC gene. The clonal relatedness of the AmpC-over-expressing isolates was assessed by pulsed-field gel electrophoresis. In addition, the ampC and ampR gene sequences were determined by PCR and sequencing. For comparison, two standard wild-type strains (PAO1 and ATCC 27853) and three multidrug-susceptible isolates were used as controls. AmpC over-expression was confirmed in 14 ceftazidime-resistant isolates (overall prevalence rate, 18.4%), belonging to seven distinct clones. The most prevalent point mutations in ampC were G27D, V205L and G391A. Point mutations in ampR were also detected in eight ceftazidime-resistant isolates. AmpC over-expression appears to be a significant mechanism of ,-lactam resistance in P. aeruginosa. Understanding the prevalence and mechanisms of ,-lactam resistance in P. aeruginosa may guide the choice of empirical therapy for nosocomial infections in hospitals. [source]


The emergence and implications of metallo-,-lactamases in Gram-negative bacteria

CLINICAL MICROBIOLOGY AND INFECTION, Issue 2005
T. R. Walsh
Abstract The increase in Gram-negative broad-spectrum antibiotic resistance is worrisome, particularly as there are few, if any, ,,pipeline'' antimicrobial agents possessing suitable activity against Pseudomonas spp. or Acinetobacter spp. The increase in resistance will be further enhanced by the acquisition of metallo-,-lactamase (MBL) genes that can potentially confer broad-spectrum ,-lactam resistance. These genes encode enzymes that can hydrolyse all classes of ,-lactams and the activity of which cannot be neutralised by ,-lactamase inhibitors. MBL genes are often associated with aminoglycoside resistant genes and thus bacteria that possess MBL genes are often co-resistant to aminoglycosides, further compromising therapeutic regimes. Both types of genes can be found as gene cassettes carried by integrons that in turn are embedded within transposons providing a highly ambulatory genetic element. The dissemination of MBL genes is typified by the spread of blaVIM-2, believed to originate from a Portuguese patient in 1995, and is now present in over 20 counties. The increase in international travel is likely to be a contributory factor for the ascendancy of mobile MBL genes as much as the mobility among individual bacteria. Fitness, acquisition and host dependency are key areas that need to be addressed to enhance our understanding of how antibiotic resistance spreads. There is also a pressing need for new, and hopefully novel, compounds active against pan-resistant Gram-negative bacteria , a growing problem that needs to be addressed by both government and industry. [source]