Subtilomycin: A New Lantibiotic from Bacillus subtilis Strain MMA7 Isolated from the Marine Sponge Haliclona simulans

Phelan, Robert W.; Barret, Matthieu; Cotter, Paul D.; O’Connor, Paula M.; Chen, Rui; Morrissey, John P.; Dobson, Alan D. W.; O’Gara, Fergal; Barbosa, Teresa M.

doi:10.3390/md11061878

Cited by 79 publications

(71 citation statements)

References 45 publications

(72 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several lantibiotics have been produced by the Bacillus group, especially the most productive Bacillus subtilis group, like subtilin from B. subtilis ATCC 6633 (16), ericin S and A from B. subtilis strain A1/3 (17), entianin from B. subtilis subsp. spizizenii DSM 15029 T (18), and recently discovered subtilomycin from marinederived B. subtilis MMA7 (19). Some lantibiotics have also been identified in other Bacillus species, like haloduracin from Bacillus halodurans C-125 (20), lichenicidin from Bacillus licheniformis DSM 13 (21), mersacidin from Bacillus sp.…”

mentioning

confidence: 99%

Cerecidins, Novel Lantibiotics from Bacillus cereus with Potent Antimicrobial Activity

Wang

Zhang

Teng

et al. 2014

Appl Environ Microbiol

View full text Add to dashboard Cite

Lantibiotics are ribosomally synthesized and posttranslationally modified antimicrobial peptides that are widely produced by Gram-positive bacteria, including many species of the Bacillus group. In the present study, one novel gene cluster coding lantibiotic cerecidins was unveiled in Bacillus cereus strain As 1.1846 through genomic mining and PCR screening. The designated cer locus is different from that of conventional class II lantibiotics in that it included seven tandem precursor cerA genes, one modification gene (cerM), two processing genes (cerT and cerP), one orphan regulator gene (cerR), and two immunity genes (cerF and cerE). In addition, one unprecedented quorum sensing component, comQXPA, was inserted between cerM and cerR. The expression of cerecidins was not detected in this strain of B. cereus, which might be due to repressed transcription of cerM. We constitutively coexpressed cerA genes and cerM in Escherichia coli, and purified precerecidins were proteolytically processed with the endoproteinase GluC and a truncated version of putative serine protease CerP. Thus, two natural variants of cerecidins A1 and A7 were obtained which contained two terminal nonoverlapping thioether rings rarely found in lantibiotics. Both cerecidins A1 and A7 were active against a broad spectrum of Gram-positive bacteria. Cerecidin A7, especially its mutant Dhb13A, showed remarkable efficacy against multidrug-resistant Staphylococcus aureus (MDRSA), vancomycin-resistant Enterococcus faecalis (VRE), and even Streptomyces.

show abstract

mentioning

confidence: 99%

Cerecidins, Novel Lantibiotics from Bacillus cereus with Potent Antimicrobial Activity

Wang

Zhang

Teng

et al. 2014

Appl Environ Microbiol

View full text Add to dashboard Cite

show abstract

“…Paenibacillin is a lantibiotic produced by the strain Paenibacillus polymyxa OSY-DF (14), and its structure has been elucidated (15); however, the paenibacillin biosynthetic gene cluster has not yet been reported. Since it shows high sequence similarity (54%) to subtilomycin, the structure of subtilomycin has been proposed using the structure of paenibacillin as a template (13). However, no molecular biological evidence has been provided to validate this proposed biosynthetic gene cluster.…”

mentioning

confidence: 99%

“…Subtilomycin is a recently identified lantibiotic produced by B. subtilis strain MMA7 isolated from the marine sponge Haliclona simulans, and it shows a broad spectrum of activity against Grampositive bacteria, including drug-resistant pathogens (13). The relationship between subtilomycin and its gene cluster was established based on the close match between the N-terminal amino acid sequence and the 5=-end sequence of the structural gene subA.…”

mentioning

confidence: 99%

ApnI, a Transmembrane Protein Responsible for Subtilomycin Immunity, Unveils a Novel Model for Lantibiotic Immunity

Deng

Zhu

et al. 2014

Appl Environ Microbiol

View full text Add to dashboard Cite

Subtilomycin was detected from the plant endophytic strain Bacillus subtilis BSn5 and was first reported from B. subtilis strain MMA7. In this study, a gene cluster that has been proposed to be related to subtilomycin biosynthesis was isolated from the BSn5 genome and was experimentally validated by gene inactivation and heterologous expression. Comparison of the subtilomycin gene cluster with other verified related lantibiotic gene clusters revealed a particular organization of the genes apnI and apnT downstream of apnAPBC, which may be involved in subtilomycin immunity. Through analysis of expression of the apnI and/or apnT genes in the subtilomycin-sensitive strain CU1065 and inactivation of apnI and apnT in the producer strain BSn5, we showed that the single gene apnI, encoding a putative transmembrane protein, was responsible for subtilomycin immunity. To our knowledge, evidence for lantibiotic immunity that is solely dependent on a transmembrane protein is quite rare. Further bioinformatic analysis revealed the abundant presence of ApnI-like proteins that may be responsible for lantibiotic immunity in Bacillus and Paenibacillus. We cloned the paeI gene, encoding one such ApnI-like protein, into CU1065 and showed that it confers resistance to paenibacillin. However, no cross-resistance was detected between ApnI and PaeI, even though subtilomycin and paenibacillin share similar structures, suggesting that the protection provided by ApnI/ApnI-like proteins involves a specific-sequence recognition mechanism. Peptide release/binding assays indicated that the recombinant B. subtilis expressing apnI interacted with subtilomycin. Thus, ApnI represents a novel model for lantibiotic immunity that appears to be common.

show abstract

“…Bacillus amyloliquefaciens GA1 amylolysin (structure undetermined) 323 Bacillus subtilis MMA7 subtilomycin (structure undetermined) 324 The genus Bacillus is ubiquitous and tolerates adverse and extreme conditions, such as high temperatures, pH and salinity, allowing its survival and adaptation to a diverse range of terrestrial and marine environments. 325 Bioactive chemistry from several marine-derived Bacillus sp.…”

mentioning

confidence: 99%

“…[326][327][328][329] Among the range of bioactive molecules produced by marine Bacillus sp., RiPPs are an underexplored class of molecules with only a few isolated from marine bacteria. 324 In our studies we ventured into an in silico investigation of a cone snail-derived Bacillus sp. The genomic DNA from Bacillus sp.…”

mentioning

confidence: 99%

Microbial biodiscovery: Exploring venomous animal associated microbes as sources of new chemical diversity

Iniguez¹

View full text Add to dashboard Cite

Microorganisms produce a large number of medically relevant small molecules through unique biosynthetic mechanisms. These small molecules have been widely used to develop drugs to treat a range of infectious diseases, cancers and other pathologies. In their natural environment microorganisms use these small molecules for signalling or defence. As microorganisms have adapted to different environments, they have greatly expanded their chemical profile and thus the investigation of microorganisms from new environments has often led to the discovery of novel chemistry.Microbes often exist in association with higher eukaryotic hosts and are therefore exposed to unique environments and thus produce unique chemistry. The host organism can benefit by utilising microbial metabolites for their own defence against infections, predators, and for chemical signalling. Interestingly, some venomous animals such as puffer fish and the blue ringed octopus utilise toxins produced by associated microbes to defend against predators. However this chemistry remains largely unexplored for the vast majority of venomous animals. In this study, we investigated metabolites from microbes associated with venomous animals including spiders, centipedes, cone snails, scorpions and wasps.We cultivated microbes from 15 venomous animals to produce a library of ~360 strains. The Chapter 1 Reviews the current status of drug discovery and symbiotic microbial strains involved in producing bioactive metabolites Poster.

show abstract

Subtilomycin: A New Lantibiotic from Bacillus subtilis Strain MMA7 Isolated from the Marine Sponge Haliclona simulans

Cited by 79 publications

References 45 publications

Cerecidins, Novel Lantibiotics from Bacillus cereus with Potent Antimicrobial Activity

Cerecidins, Novel Lantibiotics from Bacillus cereus with Potent Antimicrobial Activity

ApnI, a Transmembrane Protein Responsible for Subtilomycin Immunity, Unveils a Novel Model for Lantibiotic Immunity

Microbial biodiscovery: Exploring venomous animal associated microbes as sources of new chemical diversity

Contact Info

Product

Resources

About