The growing demand to fulfill the needs of present-day medicine in terms of novel effective molecules has lead to reexamining some of the old and known bacterial secondary metabolites. Bacterial prodigiosins (prodiginines) have a long history of being re markable multipurpose compounds, best examined for their anticancer and antimalarial activities. Production of prodigiosin in the most common producer strain Serratia marcescens has been described in great detail. However, few reports have discussed the ecophysiological roles of these molecules in the producing strains, as well as their antibiotic and UV-protective properties. This review describes recent advances in the production process, biosynthesis, properties, and applications of bacterial prodigiosins. Special emphasis is put on undecylprodigiosin which has generally been a less studied member of the prodigiosin family. In addition, it has been suggested that proteins involved in undecylprodigiosin synthesis, RedG and RedH, could be a useful addition to the biocatalytic toolbox being able to mediate regio- and stereoselective oxidative cyclization. Judging by the number of recent references (216 for the 2007-2013 period), it has become clear that undecylprodigiosin and other bacterial prodigiosins still hold surprises in terms of valuable properties and applicative potential to medical and other industrial fields and that they still deserve continuing research curiosity.

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Copper(ii) complexes with aromatic nitrogen-containing heterocycles are a new class of quorum sensing inhibitors that attenuate virulence without a pronounced effect on the bacterial growth, thus offering a lower risk for resistance development.

Combination therapy may be applied in the case of gold(iii) and silver(i) complexes with aromatic nitrogen-containing heterocycles to improve their antimicrobial activity and reduce toxic-side effects.

The 16S rRNA methyltransferase Sgm from "Micromonospora zionensis" confers resistance to aminoglycoside antibiotics by specific modification of the 30S ribosomal A site. Sgm is a member of the FmrO family, distant relatives of the S-adenosyl-L-methionine (SAM)-dependent RNA subfamily of methyltransferase enzymes. Using amino acid conservation across the FmrO family, seven putative key amino acids were selected for mutation to assess their role in forming the SAM cofactor binding pocket or in methyl group transfer. Each mutated residue was found to be essential for Sgm function, as no modified protein could effectively support bacterial growth in liquid media containing gentamicin or methylate 30S subunits in vitro. Using isothermal titration calorimetry, Sgm was found to bind SAM with a K D (binding constant) of 17.6 M, and comparable values were obtained for one functional mutant (N179A) and four proteins modified at amino acids predicted to be involved in catalysis in methyl group transfer. In contrast, none of the G135, D156, or D182 Sgm mutants bound the cofactor, confirming their role in creating the SAM binding pocket. These results represent the first functional characterization of any FmrO methyltransferase and may provide a basis for a further structurefunction analysis of these aminoglycoside resistance determinants.Antibiotic resistance by rRNA methylation is a frequently used mechanism among macrolide and aminoglycoside antibiotic-producing actinomycete strains (8). Members of the FmrO protein family, named after fortimicin A, the resistance methyltransferase (MT) from Micromonospora olivasterospora (25), methylate 16S rRNA and thus protect bacteria against the action of aminoglycoside antibiotics. Like the majority of MT enzymes, they are dependent upon the methyl donor S-adenosyl-L-methionine (SAM) as a cofactor.Two 16S rRNA modifications are most commonly employed by aminoglycoside-producing actinomycetes, the guanine-N7 methylation of G1405 (m 7 N G1405) and the adenine-N1 methylation of A1408 (m 1 N A1408) (4, 8). To date, m 1 N A1408 MTs were observed only among aminoglycoside producers, except for one instance of plasmid-mediated A1408 NpmA MT found in a clinically isolated Escherichia coli isolate that confers pan-aminoglycoside resistance among pathogenic bacteria (33). In contrast, a significantly increased spread of m 7 N G1405 MTs among various gram-negative pathogens from both clinical and veterinary isolates has been observed recently (9).Around 130 members of the SAM-dependent MT family have been classified (EC 2.1.1.X) based on their substrate specificity (small molecule, lipid, protein, or nucleic acid) and on the atom targeted for methylation. Despite sharing almost no sequence similarity with other enzymes, actinomycete MTs are remote relatives of the RNA MT subfamily of SAM-dependent MTs. However, the limited overall sequence similarity and "domain swapping" make inference about the structure of the FmrO family very difficult compared to other SAM-dependent MT families. Structural...