Disease relevance of Zwittermicin A

• This study elucidated the genetic mechanisms of zwittermicin A resistance in E. coli [1].
• Zwittermicin A resistance gene from Bacillus cereus [2].
• Zwittermicin A represents a new chemical class of antibiotic and has diverse biological activities, including suppression of oomycete diseases of plants and potentiation of the insecticidal activity of Bacillus thuringiensis [3].
• ZmaR is a resistance determinant of unusual abundance in the environment and confers on gram-positive and gram-negative bacteria resistance to zwittermicin A, a novel broad-spectrum antibiotic produced by species of Bacillus [4].
• We found that most isolates of B. cereus that were sensitive to phage P7 or inhibited the growth of Erwinia herbicola produced zwittermicin A; therefore, phage typing and E. herbicola inhibition provided indirect, but rapid screening tests for identification of zwittermicin A-producing isolates [5].

High impact information on Zwittermicin A

• The rpoB and rpoC mutants suggested that zwittermicin A might inhibit transcription, DNA replication, DNA gyrase or topoisomerase I; however, we found no further evidence to support any of these as the target for zwittermicin A [1].
• A second class of zwittermicin A-resistant mutants was aminoglycoside sensitive and was affected in rpoB and rpoC, genes that encode subunits of RNA polymerase [1].
• Zwittermicin A is a novel aminopolyol antibiotic that represents a new structural class of antibiotic and has diverse biological activities, including the suppression of plant disease and the ability to inhibit prokaryotic and eukaryotic cells [1].
• The mutant analysis, coupled with physiological data, indicated an association between the electrical membrane potential (deltapsi) component of PMF and zwittermicin A sensitivity [1].
• The results suggest that deltapsi drives zwittermicin A uptake, and that, unlike other antibiotics for which resistance maps in rpoB or rpoC, zwittermicin A does not cause the rapid cessation of DNA or RNA synthesis, suggesting a unique mechanism of antibiosis [1].

Biological context of Zwittermicin A

• ZmaR, a novel and widespread antibiotic resistance determinant that acetylates zwittermicin A [4].
• Genetics of zwittermicin a production by Bacillus cereus [3].
• Subcloning and mutagenesis defined a genetic locus, designated zmaR, on a 1.2-kb fragment of DNA that conferred zwittermicin A resistance on E. coli [2].
• The nucleotide sequence of 2.7kb of DNA flanking the zwittermicin A self-resistance gene, zmaR, from B. cereus UW85 revealed three open reading frames (ORFs) [6].
• Corresponding fragments were not detected in mutants of B. cereus UW85 that were sensitive to zwittermicin A, and the plasmids carrying zmaR restored resistance to the zwittermicin A-sensitive mutants, indicating that zmaR was deleted in the zwittermicin A-sensitive mutants and that zmaR is functional in B. cereus [2].

Associations of Zwittermicin A with other chemical compounds

• Purified ZmaR protein inactivated zwittermicin A, and biochemical assays for acetyltransferase activity with [14C]acetyl coenzyme A demonstrated that ZmaR catalyzes the acetylation of zwittermicin A with acetyl coenzyme A as a donor group, suggesting that ZmaR may constitute a new class of acetyltransferases [4].
• The results show that B. cereus cultures affect zoospore behavior in the presence of roots, and B. cereus-produced antibiotics, zwittermicin A and kanosamine, contribute to disease suppression and inhibition of germ tube elongation in the presence of the plant root [7].

Gene context of Zwittermicin A

• The assay for phage P7 sensitivity was particularly useful because of its simplicity and rapidity and because 22 of the 23 P7-sensitive isolates tested produced zwittermicin A [5].
• Additionally, nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) homologs are present, suggesting that zwittermicin A is synthesized by a mixed NRPS/PKS pathway [3].
• Insertional inactivation demonstrated that orf2 is necessary for zwittermicin A production and that zmaR is necessary for high-level resistance to zwittermicin A but is not required for zwittermicin A production [6].

Analytical, diagnostic and therapeutic context of Zwittermicin A

• Sixteen random oligonucleotide primers were tested in PCR, and one primer was identified that generated a fragment of 0.48 kb or 0.49 kb from total DNA from 26 of 28 strains known to produce zwittermicin A, whereas PCR with this primer did not generate bands of that size from 16 of 20 non-producing strains [8].
• In an in vitro seedling bioassay of disease suppression, the antibiotics, zwittermicin A and kanosamine, suppressed disease singly or together, although UW85 culture suppressed disease more effectively than did the antibiotics [7].

References