Mutacin 1140 and nisin A are peptide antibiotics that belong to the lantibiotic family. N-Terminal rings A and B of nisin A and mutacin 1140 (lipid II-binding domain) share many structural and sequence similarities. Nisin A binds lipid II and thus disrupts cell wall synthesis and also forms transmembrane pores. Very little is known about mutacin 1140 in this regard. We performed fluorescence-based studies using a bacteria-mimetic membrane system. The results indicated that lipid II monomers are arranged differently in the mutacin 1140 complex than in the nisin A complex. These differences in complex formation may be attributed to the fact that nisin A uses lipid II to form a distinct pore complex, while mutacin 1140 does not form pores in this membrane system. Further experiments demonstrated that the mutacin 1140-lipid II and nisin A-lipid II complexes are very stable and capable of withstanding competition from each other. Transmembrane electrical potential experiments using a Streptococcus rattus strain, which is sensitive to mutacin 1140, demonstrated that mutacin 1140 does not form pores in this strain even at a concentration 8 times higher than the minimum inhibitory concentration (MIC). Circular complexes of mutacin 1140 and nisin A were observed by electron microscopy, providing direct evidence for a lateral assembly mechanism for these antibiotics. Mutacin 1140 did exhibit a membrane disruptive function in another commonly used artificial bacterial membrane system, and its disruptive activity was enhanced by increasing amounts of anionic phospholipids.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/bi701262z | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Evaluation of analogs of mutacin 1140 in systemic and cutaneous methicillin-resistant infection models in mice.
Front Microbiol
December 2022
Antimicrobial Division, Sano Chemicals Inc., Bryan, TX, United States.
Mutacin 1140 (Mu1140) is a potent antibiotic against Gram-positive bacteria, such as . The antibiotic is produced by the oral bacterium and is a member of the epidermin family of type AI lantibiotics. The antibiotic exerts its inhibitory activity by binding to the cell wall precursor lipid II, blocking cell wall synthesis, and by disrupting bacterial membranes.
View Article and Find Full Text PDFLipid II Binding and Transmembrane Properties of Various Antimicrobial Lanthipeptides.
J Chem Theory Comput
January 2022
Oragenics Inc., Alachua, Florida 32615, United States.
There has been an alarming rise in antibacterial resistant infections in recent years due to the widespread use of antibiotics, and there is a dire need for the development of new antibiotics utilizing novel modes of action. Lantibiotics are promising candidates to engage in the fight against resistant strains of bacteria due to their unique modes of action, including interference with cell wall synthesis by binding to lipid II and creating pores in bacterial membranes. In this study, we use atomic-scale molecular dynamics computational studies to compare both the lipid II binding ability and the membrane interactions of five lanthipeptides that are commonly used in antimicrobial research: nisin, Mutacin 1140 (MU1140), gallidermin, NVB302, and NAI107.
View Article and Find Full Text PDFGenome-Guided Mass Spectrometry Expedited the Discovery of Paraplantaricin TC318, a Lantibiotic Produced by Strain Isolated From Cheese.
Front Microbiol
July 2020
Department of Food Science and Technology, The Ohio State University, Columbus, OH, United States.
Article Synopsis
- - Health professionals are looking for effective alternatives to current antimicrobials due to increasing resistance among pathogens, prompting a study to find new bacteriocins from lactic acid bacteria (LAB) for use as preservatives.
- - A LAB strain called OSY-TC318, isolated from Turkish cheese, was discovered to inhibit multiple pathogenic bacteria, and was identified using genome-guided mass spectrometry (MS) and genomic analysis.
- - The study identified a novel lantibiotic produced by OSY-TC318, named paraplantaricin TC318, detailing its molecular characteristics and highlighting its potential as a new antimicrobial agent distinct from existing ones.
Complete synthesis of the bicyclic ring of a mutacin analog with orthogonally protected lanthionine via solid-phase intracyclization.
J Pept Sci
November 2019
Oragenics, Department of Research and Development, Oragenics, Inc., Alachua, Florida, U.S.A.
Mutacin 1140 (MU1140) is a naturally occurring lantibiotic derived from posttranslational modifications of a ribosomally synthesized peptide during the fermentation of a bacterium called Streptococcus mutans, the etiological agent of dental cavities. A practical approach for chemically synthesizing lantibiotics would be a valuable tool to expand the MU1140 library with additional semisynthetic analogs. In turn, an expanded library may prove useful to explore additional therapeutic indications for this pipeline of novel compounds.
View Article and Find Full Text PDFMolecular mechanisms of pore formation and membrane disruption by the antimicrobial lantibiotic peptide Mutacin 1140.
Phys Chem Chem Phys
June 2019
Department of Physics, Florida International University, Miami, FL 33199, USA. and Biomolecular Sciences Institute, Florida International University, Miami, FL 33199, USA.
The emergence of antibiotic-resistance is a major concern to global human health and identification of novel antibiotics is critical to mitigate the threat. Mutacin 1140 (MU1140) is a promising antimicrobial lanthipeptide and is effective against Gram-positive bacteria. Like nisin, MU1140 targets and sequesters lipid II and interferes with its function, which results in the inhibition of bacterial cell wall synthesis, and leads to bacteria cell lysis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!