Structural and Functional Aspects of Class A Carbapenemases.

The fight against infectious diseases is probably one of the greatest public health challenges faced by our society, especially with the emergence of carbapenem-resistant gram-negatives that are in some cases pan-drug resistant. Currently,β-lactamase-mediated resistance does not spare even the newest and most powerful β-lactams (carbapenems), whose activity is challenged by carbapenemases. The worldwide dissemination of carbapenemases in gram-negative organisms threatens to take medicine back into the pre-antibiotic era since the mortality associated with infections caused by these superbugs is very high, due to limited treatment options. Clinically-relevant carbapenemases belong either to metallo-β- lactamases (MBLs) of Ambler class B or to serine-β-lactamases (SBLs) of Ambler class A and D enzymes. Class A carbapenemases may be chromosomally-encoded (SME, NmcA, SFC-1, BIC-1, PenA, FPH-1, SHV-38), plasmid-encoded (KPC, GES, FRI-1) or both (IMI). The plasmid-encoded enzymes are often associated with mobile elements responsible for their mobilization. These enzymes, even though weakly related in terms of sequence identities, share structural features and a common mechanism of action. They variably hydrolyse penicillins, cephalosporins, monobactams, carbapenems, and are inhibited by clavulanate and tazobactam. Three-dimensional structures of class A carbapenemases, in the apo form or in complex with substrates/inhibitors, together with site-directed mutagenesis studies, provide essential input for identifying the structural factors and subtle conformational changes that influence the hydrolytic profile and inhibition of these enzymes. Overall, these data represent the building blocks for understanding the structure-function relationships that define the phenotypes of class A carbapenemases and can guide the design of new molecules of therapeutic interest

National survey of colistin resistance among carbapenemase-producing Enterobacteriaceae and outbreak caused by colistin-resistant OXA-48-producing Klebsiella pneumoniae, France, 2014

From January 2014 to December 2014, 972 consecutive non-replicate carbapenemase-producing Enterobacteriaceae isolates from colonised or infected patients were collected at the Associated French National Reference Centre as part of the French national survey on antimicrobial resistance. It included 577 Klebsiella spp. (59%), 236 Escherichia coli (24%), 108 Enterobacter spp. (11%), 50 Citrobacter spp. (5%), and a single Salmonella spp. isolate (0.1%). Of 561 K. pneumoniae isolates, 35 were found to be resistant to colistin (6.2%). PFGE analysis revealed a clonal outbreak involving 15 K. pneumoniae isolates belonging to sequence type ST11, recovered in a single hospital in the Picardie region in northern France. Those clonally related isolates showed variable levels of resistance to colistin, ranging from 4 to 64 mg/L. They harboured the blaOXA-48 carbapenemase gene and the blaCTX-M-15 extended-spectrum beta-lactamase gene. Among the 91 Enterobacter cloacae isolates, seven were resistant to colistin and produced different types of carbapenemases. Surprisingly, none of the E. coli and Citrobacter spp. isolates showed resistance to colistin. This national survey including carbapenemase-producing isolates recovered in 2014 reported a high rate of colistin resistance in K. pneumoniae and E. cloacae (6.2% and 7.7%, respectively) in France

Draft Genome Sequence of the Serratia rubidaea CIP 103234T Reference Strain, a Human-Opportunistic Pathogen.

We provide here the first genome sequence of a Serratia rubidaea isolate, a human-opportunistic pathogen. This reference sequence will permit a comparison of this species with others of the Serratia genus

Whole-Genome Sequence of a European Clone II and OXA-72-Producing Acinetobacter baumannii Strain from Serbia.

We report here the draft genome sequence of a carbapenem-resistant Acinetobacter baumannii strain isolated from a patient, a strain which previously stayed in Serbia. This isolate possessed the blaOXA-72 carbapenemase gene. The draft genome sequence consists of a total length of 3.91 Mbp, with an average G+C content of 38.8%

Dissemination of carbapenemase-producing Enterobacteriaceae in France, 2012

Objectives Carbapenem-resistant Enterobacteriaceae isolates (n = 1485) were received at the French Associated National Reference Center for Antibiotic Resistance in 2012 and were characterized for their mechanism of resistance to carbapenems. Methods Carbapenemase production was detected using the biochemical-based Carba NP test, based on the detection of in vitro hydrolysis of imipenem. All isolates with a positive Carba NP test result were characterized by PCR and sequencing. Results Carbapenemase production was identified in 23.1% of the isolates. The main carbapenemase type identified was OXA-48 and derivatives (75.5%). An overseas source was clearly demonstrated for only 27.6% of the isolates. Conclusions OXA-48 and derivatives are now the most prevalent carbapenemases in France, with a possible spread of these producers in the communit