Antimicrobial mechanism of lantibiotics

Islam, Mohammad Riazul; Nagao, Jun Ichi; Zendo, Takeshi; Sonomoto, Kenji

doi:10.1042/bst20120190

Cited by 101 publications

(84 citation statements)

References 40 publications

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“…Lantibiotics such as nisin and lacticin 3147 form pores in the mycobacterial cell membrane which result in dissipation of ⌬ ( Fig. 1) (several studies have investigated the effect of these compounds in mycobacteria [61][62][63][64][65]). Although nisin is able to dissipate the membrane potential and decrease ATP levels in mycobacteria, the MIC values for various mycobacterial strains are very high and not comparable to those of current anti-TB drugs (62).…”

Section: Drugs That Target the Etcmentioning

confidence: 99%

Energy Metabolism and Drug Efflux in Mycobacterium tuberculosis

Black

Warren

Louw

et al. 2014

Antimicrob Agents Chemother

115

100

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cThe inherent drug susceptibility of microorganisms is determined by multiple factors, including growth state, the rate of drug diffusion into and out of the cell, and the intrinsic vulnerability of drug targets with regard to the corresponding antimicrobial agent. Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), remains a significant source of global morbidity and mortality, further exacerbated by its ability to readily evolve drug resistance. It is well accepted that drug resistance in M. tuberculosis is driven by the acquisition of chromosomal mutations in genes encoding drug targets/promoter regions; however, a comprehensive description of the molecular mechanisms that fuel drug resistance in the clinical setting is currently lacking. In this context, there is a growing body of evidence suggesting that active extrusion of drugs from the cell is critical for drug tolerance. M. tuberculosis encodes representatives of a diverse range of multidrug transporters, many of which are dependent on the proton motive force (PMF) or the availability of ATP. This suggests that energy metabolism and ATP production through the PMF, which is established by the electron transport chain (ETC), are critical in determining the drug susceptibility of M. tuberculosis. In this review, we detail advances in the study of the mycobacterial ETC and highlight drugs that target various components of the ETC. We provide an overview of some of the efflux pumps present in M. tuberculosis and their association, if any, with drug transport and concomitant effects on drug resistance. The implications of inhibiting drug extrusion, through the use of efflux pump inhibitors, are also discussed.

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Section: Drugs That Target the Etcmentioning

confidence: 99%

Energy Metabolism and Drug Efflux in Mycobacterium tuberculosis

Black

Warren

Louw

et al. 2014

Antimicrob Agents Chemother

115

100

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“…19) Lacticin Q showed the activity even when lipid II was blocked by vancomycin, whereas lipid II is the docking molecule necessary for the action of lantibiotics such as nisin A and lacticin 3147. 5,36,37) Further liposomal studies have indicated that lacticin Q induces high membrane permeabilization without any specific docking molecule. 36,38) Moreover, in the action of lacticin Q, peptide translocation and lipid flip-flop occurred simultaneously with pore formation on a model membrane.…”

Section: Structural Determination and Characterization Of Novel Lmentioning

confidence: 99%

Screening and Characterization of Novel Bacteriocins from Lactic Acid Bacteria

Zendo

2013

Bioscience, Biotechnology, and Biochemistry

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Bacteriocins produced by lactic acid bacteria (LAB) are expected to be safe antimicrobial agents. While the best studied LAB bacteriocin, nisin A, is widely utilized as a food preservative, various novel ones are required to control undesirable bacteria more effectively. To discover novel bacteriocins at the early step of the screening process, we developed a rapid screening system that evaluates bacteriocins produced by newly isolated LAB based on their antibacterial spectra and molecular masses. By means of this system, various novel bacteriocins were identified, including a nisin variant, nisin Q, a two-peptide bacteriocin, lactococcin Q, a leaderless bacteriocin, lacticin Q, and a circular bacteriocin, lactocyclicin Q. Moreover, some LAB isolates were found to produce multiple bacteriocins. They were characterized as to their structures, mechanisms of action, and biosynthetic mechanisms. Novel LAB bacteriocins and their biosynthetic mechanisms are expected for applications such as food preservation and peptide engineering.

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“…The leakage of essential metabolites from these cells results in death of the bacteria. Targeting of lipid II by bacteriocins is a common mechanism of action (3)(4)(5). Other mechanisms include the targeting of phosphotransferase systems (6,7), acting as Trojan horses (8,9), parasitizing iron uptake pathways (10) and causing the collapse of membrane potential, together with leakage of ions and/or a decrease in intracellular ATP concentrations (11).…”

mentioning

confidence: 99%

The Phosphoenolpyruvate:Sugar Phosphotransferase System Is Involved in Sensitivity to the Glucosylated Bacteriocin Sublancin

Gonzalo

Denham

Mars

et al. 2015

Antimicrob Agents Chemother

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The mode of action of a group of glycosylated antimicrobial peptides known as glycocins remains to be elucidated. In the current study of one glycocin, sublancin, we identified the phosphoenolpyruvate:sugar phosphotransferase system (PTS) of Bacillus species as a key player in bacterial sensitivity. Sublancin kills several Gram-positive bacteria, such as Bacillus species and Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). Unlike other classes of bacteriocins for which the PTS is involved in their mechanism of action, we show that the addition of PTS-requiring sugars leads to increased resistance rather than increased sensitivity, suggesting that sublancin has a distinct mechanism of action. Collectively, our present mutagenesis and genomic studies demonstrate that the histidine-containing phosphocarrier protein (HPr) and domain A of enzyme II (PtsG) in particular are critical determinants for bacterial sensitivity to sublancin. Bacteriocins are ribosomally synthesized peptides produced by a wide range of bacterial species. These bacteriocins endow the producing bacteria with a competitive advantage in their respective niche. Many bacteriocins are heavily posttranslationally processed during their biosynthesis, and these modifications are required for activity (1). Nisin is the best-studied bacteriocin and belongs to the lantibiotic family (2). The mode of action of nisin involves binding to lipid II, which prevents further cell wall synthesis, followed by the formation of pores within the membrane. The leakage of essential metabolites from these cells results in death of the bacteria. Targeting of lipid II by bacteriocins is a common mechanism of action (3-5). Other mechanisms include the targeting of phosphotransferase systems (6, 7), acting as Trojan horses (8, 9), parasitizing iron uptake pathways (10) and causing the collapse of membrane potential, together with leakage of ions and/or a decrease in intracellular ATP concentrations (11). There is much interest in bacteriocins for use in the control of bacterial infections and therefore in their mechanisms of action.Sublancin is a bacteriocin produced by the Gram-positive soil bacterium Bacillus subtilis strain 168. It is capable of killing several species of Gram-positive bacteria, such as Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) (12). Sublancin is encoded by the sunA gene on the SP␤ prophage as a prepeptide (13). The genes necessary for the synthesis of sublancin are also included in this region and are expressed from two promoters. The biosynthetic operon is made up of five individual genes, which are responsible for producing active sublancin. The sunT gene is responsible for the export of sublancin and cleavage of its leader sequence. Two thiol-disulfide oxidoreductases, encoded by bdbA (the only gene of the operon that is dispensable for active sublancin production) and bdbB, are responsible for creating the two disulfide bonds of sublancin. These disulfide bonds involve four of the five cysteine re...

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Antimicrobial mechanism of lantibiotics

Cited by 101 publications

References 40 publications

Energy Metabolism and Drug Efflux in Mycobacterium tuberculosis

Energy Metabolism and Drug Efflux in Mycobacterium tuberculosis

Screening and Characterization of Novel Bacteriocins from Lactic Acid Bacteria

The Phosphoenolpyruvate:Sugar Phosphotransferase System Is Involved in Sensitivity to the Glucosylated Bacteriocin Sublancin

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