Methicillin-Resistant Macrococcus bohemicus Encoding a Divergent SCCmecB Element.

A methicillin-resistant Macrococcus isolate from canine otitis, H889678/16/1, was whole-genome sequenced using HiSeq technology to identify the species, antimicrobial resistance determinates and their genomic context. H889678/16/1 belonged to the newly described species Macrococcus bohemicus. It encoded mecB within a novel SCCmec element most similar to that of Macrococcus canis KM45013T. This SCCmecH889678/16/1 element also encoded blaZm and fusC, but no other resistance determinates were found in the H889678/16/1 genome. The ccrA and ccrB recombinase genes within SCCmecH889678/16/1 were distinct from those previously described in staphylococci and macrococci and therefore designated here as ccrAm3 and ccrBm3. Our study represents, to the best of our knowledge, the first description of mecB being encoded by M. bohemicus and of methicillin resistance in this species. Furthermore, the SCCmec described here is highly dissimilar to other such elements and encodes novel ccr genes. Our report demonstrates a wider distribution of mecB among Macrococcus species and expands the genomic context in which mecB may be found. The potential for dissemination of mec genes from Macrococcus to related but more pathogenic Staphylococcus species highlights the need to understand the epidemiology of these genes in macrococci.

Metabolic engineering of Acremonium chrysogenum for improving cephalosporin C production independent of methionine stimulation.

BACKGROUND: Cephalosporin C (CPC) produced by Acremonium chrysogenum is one of the most important drugs for treatment of bacterial infectious diseases. As the major stimulant, methionine is widely used in the industrial production of CPC. In this study, we found methionine stimulated CPC production through enhancing the accumulation of endogenous S-adenosylmethionine (SAM). To overcome the methionine dependent stimulation of CPC production, the methionine cycle of A. chrysogenum was reconstructed by metabolic engineering. RESULTS: Three engineered strains were obtained by overexpressing the SAM synthetase gene AcsamS and the cystathionine-γ-lyase gene mecB, and disrupting a SAM dependent methyltransferase gene Acppm1, respectively. Overexpression of AcsamS resulted in fourfold increase of CPC production which reached to 129.7 µg/mL. Disruption of Acppm1 also increased CPC production (up to 135.5 µg/mL) through enhancing the accumulation of intracellular SAM. Finally, an optimum recombinant strain (Acppm1DM-mecBOE) was constructed through overexpressing mecB in the Acppm1 disruption mutant. In this strain, CPC production reached to the maximum value (142.7 µg/mL) which was 5.5-fold of the wild-type level and its improvement was totally independent of methionine stimulation. CONCLUSIONS: In this study, we constructed a recombinant strain in which the improvement of CPC production was totally independent of methionine stimulation. This work provides an economic route for improving CPC production in A. chrysogenum through metabolic engineering.

Plasmid-Encoded Transferable mecB-Mediated Methicillin Resistance in Staphylococcus aureus.

During cefoxitin-based nasal screening, phenotypically categorized methicillin-resistant Staphylococcus aureus (MRSA) was isolated and tested negative for the presence of the mecA and mecC genes as well as for the SCCmec-orfX junction region. The isolate was found to carry a mecB gene previously described for Macrococcus caseolyticus but not for staphylococcal species. The gene is flanked by ß-lactam regulatory genes similar to mecR, mecI, and blaZ and is part of an 84.6-kb multidrug-resistance plasmid that harbors genes encoding additional resistances to aminoglycosides (aacA-aphD, aphA, and aadK) as well as macrolides (ermB) and tetracyclines (tetS). This further plasmidborne ß-lactam resistance mechanism harbors the putative risk of acceleration or reacceleration of MRSA spread, resulting in broad ineffectiveness of ß-lactams as a main therapeutic application against staphylococcal infections.

Genomic Basis for Methicillin Resistance in Staphylococcus aureus.

Since the discovery of the first strain in 1961 in England, MRSA, the most notorious multidrug-resistant hospital pathogen, has spread all over the world. MRSA repeatedly turned down the challenges by number of chemotherapeutics, the fruits of modern organic chemistry. Now, we are in short of effective therapeutic agents against MRSA prevailing among immuno-compromised patients in the hospital. On top of this, we recently became aware of the rise of diverse clones of MRSA, some of which have increased pathogenic potential compared to the classical hospital-associated MRSA, and the others from veterinary sources. They increased rapidly in the community, and started menacing otherwise healthy individuals by causing unexpected acute infection. This review is intended to provide a whole picture of MRSA based on its genetic makeup as a versatile pathogen and our tenacious colonizer.

Genomic Basis for Methicillin Resistance in Staphylococcus aureus / 감염과화학요법

Since the discovery of the first strain in 1961 in England, MRSA, the most notorious multidrug-resistant hospital pathogen, has spread all over the world. MRSA repeatedly turned down the challenges by number of chemotherapeutics, the fruits of modern organic chemistry. Now, we are in short of effective therapeutic agents against MRSA prevailing among immuno-compromised patients in the hospital. On top of this, we recently became aware of the rise of diverse clones of MRSA, some of which have increased pathogenic potential compared to the classical hospital-associated MRSA, and the others from veterinary sources. They increased rapidly in the community, and started menacing otherwise healthy individuals by causing unexpected acute infection. This review is intended to provide a whole picture of MRSA based on its genetic makeup as a versatile pathogen and our tenacious colonizer.