Distribution of Genes Encoding the Trypsin-Dependent Lantibiotic Ruminococcin A among Bacteria Isolated from Human Fecal Microbiota

Marcille, F.; Gómez, Alberto Gómez; Joubert, Philippe; Ladiré, M.; Veau, G.; Clara, Antonio; Gavini, F.; Willems, Anne; Fons, Michel

doi:10.1128/aem.68.7.3424-3431.2002

Cited by 33 publications

(29 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The high gene and intergenic sequence similarity between the nsoA1 genes suggests that the triplication occurred by consecutive duplication events. This is not unprecedented -ruminococcin A, also found in the gut and induced by trypsin, contains three rumA genes in its cluster that code for the same peptide [60]. Two-component lantibiotics that contain two active structural genes are not uncommon [61].…”

Section: Discussionmentioning

confidence: 99%

Discovery of a novel lantibiotic nisin O from Blautia obeum A2-162, isolated from the human gastrointestinal tract

et al. 2017

View full text Add to dashboard Cite

A novel lanC-like sequence was identified from the dominant human gut bacterium Blautia obeum strain A2-162. This sequence was extended to reveal a putative lantibiotic operon with biosynthetic and transport genes, two sets of regulatory genes, immunity genes, three identical copies of a nisin-like lanA gene with an unusual leader peptide, and a fourth putative lanA gene. Comparison with other nisin clusters showed that the closest relationship was to nisin U. B. obeum A2-162 demonstrated antimicrobial activity against Clostridium perfringens when grown on solid medium in the presence of trypsin. Fusions of predicted nsoA structural sequences with the nisin A leader were expressed in Lactococcus lactis containing the nisin A operon without nisA. Expression of the nisA leader sequence fused to the predicted structural nsoA1 produced a growth defect in L. lactis that was dependent upon the presence of biosynthetic genes, but failed to produce antimicrobial activity. Insertion of the nso cluster into L. lactis MG1614 gave an increased immunity to nisin A, but this was not replicated by the expression of nsoI. Nisin A induction of L. lactis containing the nso cluster and nisRK genes allowed detection of the NsoA1 pre-peptide by Western hybridization. When this heterologous producer was grown with nisin induction on solid medium, antimicrobial activity was demonstrated in the presence of trypsin against C. perfringens, Clostridium difficile and L. lactis. This research adds to evidence that lantibiotic production may be an important trait of gut bacteria and could lead to the development of novel treatments for intestinal diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Discovery of a novel lantibiotic nisin O from Blautia obeum A2-162, isolated from the human gastrointestinal tract

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Although a number of two-peptide lantibiotics which are active by virtue of the combined activities of two quite different lanthionine-containing peptides exist (37), the benefits of possessing multiple highly homologous structural peptide-encoding genes is not evident. Despite this, a number of lantibiotic producers, especially among strains producing the type AII (lacticin-481-like) lantibiotics (e.g., ruminococcin A [40], mutacin K8 [56], streptococcin A-M49 [32], streptococcin A-FF22 [42], and macedocin [50]), carry multiple copies of homologous structural genes. This phenomenon has previously also been associated with the other epidermin-like peptides mutacin I (53), mutacin III (54), and mutacin BNy266 (5).…”

Section: Discussionmentioning

confidence: 99%

Production of the Bsa Lantibiotic by Community-Acquired Staphylococcus aureus Strains

Daly¹,

Upton

Sandiford

et al. 2010

J Bacteriol

View full text Add to dashboard Cite

Lantibiotics are antimicrobial peptides that have been the focus of much attention in recent years with a view to clinical, veterinary, and food applications. Although many lantibiotics are produced by food-grade bacteria or bacteria generally regarded as safe, some lantibiotics are produced by pathogens and, rather than contributing to food safety and/or health, add to the virulence potential of the producing strains. Indeed, genome sequencing has revealed the presence of genes apparently encoding a lantibiotic, designated Bsa (bacteriocin of Staphylococcus aureus), among clinical isolates of S. aureus and those associated with community-acquired methicillin-resistant S. aureus (MRSA) infections in particular. Here, we establish for the first time, through a combination of reverse genetics, mass spectrometry, and mutagenesis, that these genes encode a functional lantibiotic. We also reveal that Bsa is identical to the previously identified bacteriocin staphylococcin Au-26, produced by an S. aureus strain of vaginal origin. Our examination of MRSA isolates that produce the Panton-Valentine leukocidin demonstrates that many community-acquired S. aureus strains, and representatives of ST8 and ST80 in particular, are producers of Bsa. While possession of Bsa immunity genes does not significantly enhance resistance to the related lantibiotic gallidermin, the broad antimicrobial spectrum of Bsa strongly indicates that production of this bacteriocin confers a competitive ecological advantage on communityacquired S. aureus.

show abstract

“…This is the case with streptococcin SA-F22 which possesses 2 such genes located adjacently [49] while ruminococcin producers have three such structural genes i.e. rumA1, rumA2 and rumA3 [41,75]. Finally bovicin HJ50 has been placed in the lacticin 481 group by virtue of the similarity of the Nterminus of the unmodified propeptide with those of other lacticin 481-type lantibiotics.…”

Section: Natural Variantsmentioning

confidence: 99%

Bacterial Lantibiotics: Strategies to Improve Therapeutic Potential

Cotter

Hill²,

Ross

2005

CPPS

249

235

View full text Add to dashboard Cite

Lantibiotics are ribosomally-synthesised antimicrobial peptides produced by Gram-positive bacteria that are characterised by the presence of lanthionine and/or methyllanthionine residues. Other unusual post-translationally modified amino acids, most frequently dehydroalanine and dehydrobutyrine, can also be present. While it has been frequently suggested that these peptides have the potential to be utilised in a wide range of medical applications, to date no actual therapeutic applications have been convincingly described. More recently, however, they have been the focus of much attention as a consequence of improved biotechnological capabilities, an improved understanding of lantibiotic biosynthesis and mode of action, and their high specific activity against multi-drug resistant bacteria. This review concerns the fundamental analyses that have revealed the importance of individual amino acids in these peptides and has permitted the implementation of rational mutagenesis strategies ('intelligenetics') to alter individual residues with a view to ultimately widening the active pH range, improve stability, and enhance binding to cell wall targets with the ultimate aim of optimising their antimicrobial activity. It is hoped that as a consequence of this improved knowledge the most suitable application of individual lantibiotics will become apparent. It should also prove possible, in the near future, to generate tailor-made lantibiotics and utilise biosynthetic enzymes to incorporate modified amino acids into non-lantibiotic peptides. In the shorter term, the extensive characterisation of lantibiotics will be instrumental in reassuring drug industry regulators of their safety and facilitate the widespread application of these novel antimicrobial agents in medicine.

show abstract

Distribution of Genes Encoding the Trypsin-Dependent Lantibiotic Ruminococcin A among Bacteria Isolated from Human Fecal Microbiota

Cited by 33 publications

References 42 publications

Discovery of a novel lantibiotic nisin O from Blautia obeum A2-162, isolated from the human gastrointestinal tract

Discovery of a novel lantibiotic nisin O from Blautia obeum A2-162, isolated from the human gastrointestinal tract

Production of the Bsa Lantibiotic by Community-Acquired Staphylococcus aureus Strains

Bacterial Lantibiotics: Strategies to Improve Therapeutic Potential

Contact Info

Product

Resources

About