Despite numerous existing potent antibiotics and other antimicrobial means, bacterial infections are still a major cause of morbidity and mortality. Moreover, the need to develop additional bactericidal means has significantly increased due to the growing concern regarding multidrug-resistant bacterial strains and biofilm associated infections. Consequently, attention has been especially devoted to new and emerging nanoparticle-based materials in the field of antimicrobial chemotherapy. The present review discusses the activities of nanoparticles as an antimicrobial means, their mode of action, nanoparticle effect on drug-resistant bacteria, and the risks attendant on their use as antibacterial agents. Factors contributing to nanoparticle performance in the clinical setting, their unique properties, and mechanism of action as antibacterial agents are discussed in detail.
Traditionally, programmed cell death (PCD) is associated with eukaryotic multicellular organisms. However, recently, PCD systems have also been observed in bacteria. Here we review recent research on two kinds of genetic programs that promote bacterial cell death. The first is mediated by mazEF, a toxin–antitoxin module found in the chromosomes of many kinds of bacteria, and mainly studied in Escherichia coli. The second program is found in Bacillus subtilis, in which the skf and sdp operons mediate the death of a subpopulation of sporulating bacterial cells. We relate these two bacterial PCD systems to the ways in which bacterial populations resemble multicellular organisms.
A patient with a trauma-related left tibial infection associated with extensively drug-resistant Acinetobacter baumannii and multidrug-resistant Klebsiella pneumoniae was treated with bacteriophages and antibiotics. There was rapid tissue healing and positive culture eradication. As a result, the patient’s leg did not have to be amputated and he is undergoing rehabilitation.
mazEF is an Escherichia coli suicide module specific for a stable toxin and a labile antitoxin. Inhibiting mazEF expression appeared to activate the module to cause cell death. Here we show that several stressful conditions, including high temperatures, DNA damage, and oxidative stress, also induce mazEF -mediated cell death. We also show that this process takes place only during logarithmic growth and requires an intact relA gene.
Pseudomonas aeruginosa harbours three type VI secretion (T6S) loci. Although HSI-I has been partially studied, limited knowledge is available on the homologous loci HSI-II and HSI-III. We show that quorum sensing (QS) differentially regulates the expression of genes at all three loci. HSI-I-associated gene expression is suppressed by both the homoserine lactone transcription factor LasR and the 4-hydroxy-2-alkylquinoline (HAQ) transcriptional regulator MvfR. Conversely, both HSI-II and HSI-III loci are positively controlled by LasR and MvfR. PqsE, a key component of the MvfR regulon, is required for the expression of part of HSI-III but not HSI-II, and previously identified inhibitors of HAQ biosynthesis significantly downregulate HSI-II and -III gene expression. Animal and plant infection studies reveal that both HSI-II and -III play important roles in pathogenesis. Furthermore, analysis of a double ΔHSI-II : : III mutant suggests that these loci functionally compensate for one another in virulence. This study illustrates the contribution of the QS systems to T6S gene regulation and reveals the importance of HSI-II and -III in mediating P. aeruginosa pathogenesis. Moreover, this work provides new insights into the design and development of selective compounds that may restrict human P. aeruginosa and possibly other clinical infections.
mazEF is a toxin-antitoxin module located on many bacterial chromosomes, including those of pathogens. Here, we report that Escherichia coli mazEF -mediated cell death is a population phenomenon requiring a quorum-sensing molecule that we call the extracellular death factor (EDF). Structural analysis revealed that EDF is a linear pentapeptide, Asn-Asn-Trp-Asn-Asn. Each of the five amino acids of EDF is important for its activity.