The reported QS inhibitors include both natural and synthetic agents and can be mainly categorized in three classes: nonpeptide small molecules, peptides and proteins. These inhibitors interrupt QS by repressing signal generation, blocking signal receptors or disrupting QS signals, and provide an alternative approach to controlling microbial pathogenesis.
BackgroundBacteria are well known to form dormant persister cells that are tolerant to most antibiotics. Such intrinsic tolerance also facilitates the development of multidrug resistance through acquired mechanisms. Thus persister cells are a promising target for developing more effective methods to control chronic infections and help prevent the development of multidrug-resistant bacteria. However, control of persister cells is still an unmet challenge.Methodology/Principal FindingsWe show in this report that (Z)-4-bromo-5-(bromomethylene)-3-methylfuran-2(5H)-one (BF8) can restore the antibiotic susceptibility of Pseudomonas aeruginosa PAO1 persister cells at growth non-inhibitory concentrations. Persister control by BF8 was found to be effective against both planktonic and biofilm cells of P. aeruginosa PAO1. Interestingly, although BF8 is an inhibitor of quorum sensing (QS) in Gram-negative bacteria, the data in this study suggest that the activities of BF8 to revert antibiotic tolerance of P. aeruginosa PAO1 persister cells is not through QS inhibition and may involve other targets.ConclusionBF8 can sensitize P. aeruginosa persister cells to antibiotics.
As one of the leading causes of food
poisoning, staphylococcal enterotoxins (SEs) secreted by Staphylococcus aureus pose a serious threat to human
health. The immunoassay has become the dominant tool used for the
rapid detection of harmful bacteria and toxins as a result of its
excellent specificity. However, with regard to SEs, staphylococcal
protein A (SpA) is likely to bind with the fragment crystallizable
(Fc) terminal of the traditional antibody and result in a false positive,
limiting the practical application of this method. Therefore, to eliminate
the bottleneck problem, the sandwich immunoassay was development by
replacing the traditional antibody with a nanobody (Nb) that lacked
a Fc terminal. Using 0.5 × 107 colony-forming units,
the Nb library was constructed using Bactrian camels immunized with
staphylococcal enterotoxin B (SEB) to obtain a paired Nb against SEB
with good affinity. A sandwich enzyme-linked immunosorbent assay (ELISA)
was developed using one Nb as the capture antibody and a phage-displayed
Nb with signal-amplifying properties as the detection antibody. In
optimal conditions, the current immunoassay displayed a broad quantitative
range from 1 to 512 ng/mL and a 0.3 ng/mL limit of detection. The
recovery of spiked milk, milk powder, cheese, and beef ranged from
87.66 to 114.2%. The Nbs-ELISA was not influenced by SpA during the
detection of SEB in S. aureus food
poisoning. Therefore, the Nb developed here presented the perfect
candidates for immunoassay application during SE determination as
a result of the complete absence of SpA interference.
Persisters are a small subpopulation of bacterial cells that are dormant and extremely tolerant to antibiotics. The intrinsic antibiotic tolerance of persisters also facilitates the development of multidrug resistance through acquired mechanisms based on drug resistance genes. In this study, we demonstrate that (Z)-4-bromo-5-(bromomethylene)-3-methylfuran-2(5H)-one (BF8) can reduce persistence during Escherichia coli growth and revert the antibiotic tolerance of its persister cells. The effects of BF8 were more profound when the pH was increased from 6 to 8.5. Although BF8 is a quorum sensing (QS) inhibitor, similar effects were observed for the wild-type E. coli RP437 and its ΔluxS mutant, suggesting that these effects did not occur solely through inhibition of AI-2-mediated QS. In addition to its effects on planktonic persisters, BF8 was also found to disperse RP437 biofilms and to render associated cells more sensitive to ofloxacin. At the doses that are effective against E. coli persister cells, BF8 appeared to be safe to the tested normal mammalian cells in vitro and exhibited no long-term cytotoxicity to normal mouse tissues in vivo. These findings broadened the activities of brominated furanones and shed new light on persister control.
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