RNA-seq-based transcriptomic analysis of AHL-induced biofilm and pyocyanin inhibition in Pseudomonas aeruginosa by Lactobacillus brevis

International Microbiology - Quorum sensing (QS) regulates hundreds of genes in Pseudomonas aeruginosa, and many of which encode extracellular virulence factors. Lactobacillus as a probiotic has...     

植物精油对铜绿假单胞菌群体感应系统的抑制作用研究进展

群体感应（quorum sensing,QS）是细菌个体与个体之间的一种交流机制,广泛存在于细菌中。铜绿假单胞菌是人类的一种条件致病菌,它具有至少3种QS系统,即las、rhl和pqs系统,且各系统之间存在着级联调控关系,它们共同作用调控着该菌众多毒力基因的表达和毒力因子的产生。近年来,通过抑制铜绿假单胞菌的QS系统以控制其毒力和致病力,成为一种新型的铜绿假单胞菌感染防控策略。植物精油是一种天然的群体感应抑制剂（quorum sensing inhibitors, QSI）,多种精油活性化合物都能抑制铜绿假单胞菌的QS系统,而且尚未发现细菌对其产生耐药性。基于此,梳理了铜绿假单胞菌QS系统的组成及其级联调控关系,简要介绍了植物精油的QS抑制机制和抑制活性,并重点综述了萜烯类化合物、芳香族化合物、脂肪族化合物、含硫含氮化合物4类精油化合物对铜绿假单胞菌QS系统抑制作用的研究进展,以期为从天然化合物中发现和筛选安全、高效的细菌QSI的相关研究提供参考,并为致病菌的防控奠定理论基础。     

Multiple roles of TorD-like chaperones in the biogenesis of molybdoenzymes

Studies on cultured cells and in infection models have shown that cell density-dependent quorum-sensing (QS) controls many of the known virulence factors of Pseudomonas aeruginosa . However, it is less clear what role QS plays in chronic human lung infections associated with cystic fibrosis (CF). The involvement of QS in biofilm development, crucial to the establishment of long-term infections, suggests a role in the early stages of infection. However, the accumulation of QS mutants during chronic CF infections has been taken to indicate that any role diminishes thereafter. Here, we discuss the evidence for a continuing role for QS in P. aeruginosa CF infections, including QS activity in CF sputa and CF-relevant effects of QS-regulated products, such as pyocyanin. Bacterial population behaviour in CF is complex, and the exact roles of QS remains unclear. Therapeutic strategies directed against QS suggest that a greater understanding of bacterial populations during infection would be a valuable research goal from a clinical perspective.     

Comparative study of the biological characteristics of mucoid and non-mucoid Pseudomonas aeruginosa strains isolated from chronic respiratory infections

Morphological, culture and enzymatic characteristics, as well as virulence, susceptibility to antimicrobial agents and epidemiological markers, were studied for 100 mucoid and 100 non-mucoid Ps. aeruginosa strains isolated from chronic respiratory infections. For 10 mucoid and 10 non-mucoid strains was performed the active protection test in mice, both with inactivated germs (10(9) germs), and LPS extracted by Westphal method. It was ascertained that mucoid Ps. aeruginosa strains differ from non-mucoid strains by the slow growth on culture media, more reduced proteolytic activity (81% as compared to 99%), slow oxidation of carbohydrates (5-7 days), reduced virulence in mice (8%) or avirulence (92%), higher sensitivity to some antibiotics (amikacin, dibekacin, ticarcillin, tetracycline, cefotaxime, ceftriaxone), lysoresistance (74%) and polyagglutinability (67%). The mucoid strains ensure a reduced active protection in mice, 70% of strains did not protect the mice against the infection with virulent homologous strains, while the non-mucoid strains ensured 80%-100% protection.     

Modeling the effect of acylated homoserine lactone antagonists in Pseudomonas aeruginosa

Pseudomonas aeruginosa is a gram-negative bacterium that causes serious illnesses, particularly in immunocompromised individuals, often with a fatal outcome. The finding that the acylated homoserine lactone quorum sensing (QS) system controls the production of virulence factors in P. aeruginosa makes this system a possible target for antimicrobial therapy. It has been suggested that an N-(3-oxododecanoyl)-homoserine lactone (3O-C12-HSL) antagonist, a QS blocker (QSB), would interfere efficiently with the quorum sensing system in P. aeruginosa and thus reduce the virulence of this pathogen. In this work, a mathematical model of the QS system in P. aeruginosa has been developed. The model was used to virtually add 3O-C12-HSL antagonists that differed in their affinity for the receptor protein and for their ability to mediate degradation of the receptor. The model suggests that very small differences in these parameters for different 3O-C12-HSL antagonists can greatly affect the success of QSB based inhibition of the QS system in P. aeruginosa. Most importantly, it is proposed that the ability of the 3O-C12-HSL antagonist to mediate degradation of LasR is the core parameter for successful QSB based inhibition of the QS system in P. aeruginosa. Finally, this study demonstrates that QSBs can shift the system to a low steady state, corresponding to an uninduced state and thus, suggests that the use of 3O-C12-HSL antagonists may constitute a promising therapeutic approach against P. aeruginosa involved infections.     

Inhibitors of pathogen intercellular signals as selective anti-infective compounds

Long-term antibiotic use generates pan-resistant super pathogens. Anti-infective compounds that selectively disrupt virulence pathways without affecting cell viability may be used to efficiently combat infections caused by these pathogens. A candidate target pathway is quorum sensing (QS), which many bacterial pathogens use to coordinately regulate virulence determinants. The Pseudomonas aeruginosa MvfR-dependent QS regulatory pathway controls the expression of key virulence genes; and is activated via the extracellular signals 4-hydroxy-2-heptylquinoline (HHQ) and 3,4-dihydroxy-2-heptylquinoline (PQS), whose syntheses depend on anthranilic acid (AA), the primary precursor of 4-hydroxy-2-alkylquinolines (HAQs). Here, we identified halogenated AA analogs that specifically inhibited HAQ biosynthesis and disrupted MvfR-dependent gene expression. These compounds restricted P. aeruginosa systemic dissemination and mortality in mice, without perturbing bacterial viability, and inhibited osmoprotection, a widespread bacterial function. These compounds provide a starting point for the design and development of selective anti-infectives that restrict human P. aeruginosa pathogenesis, and possibly other clinically significant pathogens.     

Anti-infective properties of Lactobacillus fermentum against Staphylococcus aureus and Pseudomonas aeruginosa

Surgical wounds and implant-associated Staphylococcus aureus and Pseudomonas aeruginosa infections are often difficult to treat because of limited susceptibility of several of these strains to conventional antibiotics. As a result, there is a constant need for new alternative drugs. The aim of this study was to investigate the antimicrobial properties of Lactobacillus fermentum, a probiotic bacterium, which we have isolated from colonic biopsies. The inhibition of S. aureus and P. aeruginosa growth was evaluated by coincubating with L. fermentum strains. Growth inhibition was tested for several of their clinical isolates using agar well diffusion assays. For biofilm assay S. aureus and P. aeruginosa were grown on the glass slides and in 96-well plates in presence of 2.5 μg/ml culture filtrate of L. fermentum. Biofilms were photographed using confocal microscope or stained with 0.1% crystal violet. Reduction in the cytotoxicity of S. aureus and P. aeruginosa was observed in presence of 2.5 μg/ml L. fermentum-spent media. Using in vitroexperiments, we showed that L. fermentum-secreted compound(s) inhibits the growth, cytotoxicity and biofilm formation of several S. aureus and P. aeruginosa strains. Compound(s) present in the culture supernatant of L. fermentum may have promising applications in treating hospital-acquired infections.     

The occurrence of denitrification in extremely halophilic bacteria

Abstract A total of 97 aerobic and facultatively anaerobic bacteria, and 3 Candida albicans , were tested for their ability to inhibit the growth of Haemophilus influenzae . Only strains of Pseudomonas aeruginosa showed any inhibitory effect and all 5 strains tested clearly inhibited the growth of all 10 strains of H. influenzae . The inhibition of H. influenzae . by Ps. aeruginosa may play a role in the establishment of chronic Ps. aeruginosa infections in the respiratory tracts of patients with bronchiectasis and cystic fibrosis (CF).     

Furvina inhibits the 3-oxo-C12-HSL-based quorum sensing system of Pseudomonas aeruginosa and QS-dependent phenotypes

Disruption of cell–cell communication or quorum sensing (QS) is considered a stimulating approach for reducing bacterial pathogenicity and resistance. Although several QS inhibitors (QSIs) have been discovered so far their clinical use remains distant. This problem can be circumvented by searching for QSI among drugs already approved for the treatment of different diseases. In this context, antibiotics have earned special attention. Whereas at high concentrations antibiotics exert a killing effect, at lower concentrations they may act as signaling molecules and as such can modulate gene expression. In this study, the antibiotic furvina was shown to be able to cause inhibition of the 3-oxo-C12-HSL-dependent QS system of Pseudomonas aeruginosa. Furvina interacts with the LasI/LasR system. The data were validated by modeling studies. Furvina can also reduce biofilm formation and decrease the production of QS-controlled virulence factors.     

Comparative activity of tobramycin and gentamicin against Pseudomonas,Proteus and Providencia species.

Tobramycin is a new antibiotic resembling gentamicin. We measured the minimal inhibitory concentrations of these two antibiotics against five bacterial species that cause hospital-acquired infections and are resistant to many presently available antibiotics. The organisms tested were 500 strains of Pseudomones aeruginosa, 100 strains of each of Proteus rettgeri and Pr. morganii, 50 strains of Pr. vulgaris and 250 strains of Providencia stuartii. Tobramycin was 2 to 4 times more active than gentamicin against Ps. aeruginosa; all except 6 of 70 strains resistant to 4 mug/ml of gentamicin were sensitive to 4 mug/ml of tobramycin. The two antibiotics showed a similar degree of activity against the other four species. Tobramycin promises to be of particular value in the treatment of Pseudomonas infections.     

Quorum-sensing blockade as a strategy for enhancing host defences against bacterial pathogens

Conventional antibiotics target the growth and the basal life processes of bacteria leading to growth arrest and cell death. The selective force that is inherently linked to this mode of action eventually selects out antibiotic-resistant variants. The most obvious alternative to antibiotic-mediated killing or growth inhibition would be to attenuate the bacteria with respect to pathogenicity. The realization that Pseudomonas aeruginosa, and a number of other pathogens, controls much of their virulence arsenal by means of extracellular signal molecules in a process denoted quorum sensing (QS) gave rise to a new 'drug target rush'. Recently, QS has been shown to be involved in the development of tolerance to various antimicrobial treatments and immune modulation. The regulation of virulence via QS confers a strategic advantage over host defences. Consequently, a drug capable of blocking QS is likely to increase the susceptibility of the infecting organism to host defences and its clearance from the host. The use of QS signal blockers to attenuate bacterial pathogenicity, rather than bacterial growth, is therefore highly attractive, particularly with respect to the emergence of multi-antibiotic resistant bacteria.