Persister-promoting bacterial toxin TisB produces anion-selective pores in planar lipid bilayers.

Program in Physical Biology, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
FEBS letters (Impact Factor: 3.54). 06/2012; 586(16):2529-34. DOI: 10.1016/j.febslet.2012.06.021
Source: PubMed

ABSTRACT We studied membrane activity of the bacterial peptide TisB involved in persister cell formation. TisB and its analogs form multi-state ion-conductive pores in planar lipid bilayers with all states displaying similar anionic selectivity. TisB analogs differing by ±1 elementary charges show corresponding changes in selectivity. Probing TisB pores with poly-(ethylene glycol)s reveals only restricted partitioning even for the smallest polymers, suggesting that the pores are characterized by a relatively small diameter. These findings allow us to suggest that TisB forms clusters of narrow pores that are essential for its mechanism of action.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bacterial toxin-antitoxin loci consist of two genes: one encodes a potentially toxic protein, and the second, an antitoxin to repress its function or expression. The antitoxin can either be an RNA or a protein. For type I and type III loci, the antitoxins are RNAs; however, they have very different modes of action. Type I antitoxins repress toxin protein expression through interacting with the toxin mRNA, thereby targeting the mRNA for degradation or preventing its translation or both; type III antitoxins directly bind to the toxin protein, sequestering it. Along with these two very different modes of action for the antitoxin, there are differences in the functions of the toxin proteins and the mobility of these loci between species. Within this review, we discuss the major differences as to how the RNAs repress toxin activity, the potential consequences for utilizing different regulatory strategies, as well as the confirmed and potential biological roles for these loci across bacterial species.
    Toxins 08/2014; 6(8):2310-2335. · 2.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Staphylococcus aureus is an opportunistic pathogen capable of causing a variety of diseases including osteomyelitis, endocarditis, infections of indwelling devices and wound infections. These infections are often chronic and highly recalcitrant to antibiotic treatment. Persister cells appear to be central to this recalcitrance. A multitude of factors contribute to S. aureus virulence and high levels of treatment failure. These include its ability to colonize the skin and nares of the host, its ability to evade the host immune system and its development of resistance to a variety of antibiotics. Less understood is the phenomenon of persister cells and their role in S. aureus infections and treatment outcome. Persister cells occur as a sub-population of phenotypic variants that are tolerant to antibiotic treatment. This review examines the importance of persisters in chronic and relapsing S. aureus infections and proposes methods for their eradication.
    BioEssays 08/2014; · 4.84 Impact Factor
  • Source
    Journal of Internal Medicine 05/2014; · 5.79 Impact Factor


Available from
May 20, 2014