Broad Antibiotic Activity Research Articles

The potential to produce tropodithietic acid by Phaeobacter inhibens affects the assembly of microbial biofilm communities in natural seawater

Microbial secondary metabolites play important roles in biotic interactions in microbial communities and yet, we do not understand how these compounds impact the assembly and development of microbial communities. To address the implications of microbial secondary metabolite production on biotic interactions in the assembly of natural seawater microbiomes, we constructed a model system where the assembly of a natural seawater biofilm community was influenced by the addition of the marine biofilm forming Phaeobacter inhibens that can produce the antibiotic secondary metabolite tropodithietic acid (TDA), or a mutant incapable of TDA production. Because of the broad antibiotic activity of TDA, we hypothesized that the potential of P. inhibens to produce TDA would strongly affect both biofilm and planktonic community assembly patterns. We show that 1.9 % of the microbial composition variance across both environments could be attributed to the presence of WT P. inhibens, and especially genera of the Bacteriodetes were increased by the presence of the TDA producer. Moreover, network analysis with inferred putative microbial interactions revealed that P. inhibens mainly displayed strong positive associations with genera of the Flavobacteriaceae and Alteromonadaceae, and that P. inhibens acts as a keystone OTU in the biofilm exclusively due to its potential to produce TDA. Our results demonstrate the potential impact of microbial secondary metabolites on microbial interactions and assembly dynamics of complex microbial communities.

Plant-associated Bacillus mobilizes its secondary metabolites upon perception of the siderophore pyochelin produced by a Pseudomonas competitor

Bacillus velezensis is considered as model species for plant-associated bacilli providing benefits to its host such as protection against phytopathogens. This is mainly due to the potential to secrete a wide range of secondary metabolites with specific and complementary bioactivities. This metabolite arsenal has been quite well defined genetically and chemically but much remains to be explored regarding how it is expressed under natural conditions and notably how it can be modulated upon interspecies interactions in the competitive rhizosphere niche. Here, we show that B. velezensis can mobilize a substantial part of its metabolome upon the perception of Pseudomonas, as a soil-dwelling competitor. This metabolite response reflects a multimodal defensive strategy as it includes polyketides and the bacteriocin amylocyclicin, with broad antibiotic activity, as well as surfactin lipopeptides, contributing to biofilm formation and enhanced motility. Furthermore, we identified the secondary Pseudomonas siderophore pyochelin as an info-chemical, which triggers this response via a mechanism independent of iron stress. We hypothesize that B. velezensis relies on such chelator sensing to accurately identify competitors, illustrating a new facet of siderophore-mediated interactions beyond the concept of competition for iron and siderophore piracy. This phenomenon may thus represent a new component of the microbial conversations driving the behavior of members of the rhizosphere community.

Real-World Treatment of Enterococcal Infections with Daptomycin: Insights from a Large European Registry (EU-CORE).

IntroductionEvolution of antibacterial resistance in pathogenic enterococcal strains poses a growing therapeutic challenge. Daptomycin, a cyclic lipopeptide, exhibits broad antibiotic activity against Gram-positive bacteria.MethodsThe European Cubicin® Outcomes Registry and Experience, a multicenter, retrospective, non-interventional study, recorded clinical outcomes following daptomycin treatment.ResultsOverall, 472 patients (predominantly elderly Caucasian males) were treated for enterococcal infections. Of those, 72.7% received antibiotics prior to daptomycin treatment, whereas 77.1% received other antibiotics concomitantly. Failure of previous therapy, resistant or non-susceptible pathogen, and narrowing of antibiotic therapy were the main reasons for switching to daptomycin treatment. Nosocomial infections comprised 55.8% of the cohort. Bacteremia (29.9%), complicated skin and soft tissue infection (29.2%) and endocarditis (12.3%) were the most common primary infections. Clinical success was achieved in 77.1% of patients, with similar success rates across all primary infection categories. The overall clinical success rate was marginally higher (82.5% vs 74.6%, p = 0.09) with daptomycin use as first-line versus second-line therapy. Patients receiving higher doses of daptomycin exhibited the highest clinical success rates (85.7% for ≥8 mg/kg/day vs 75.8% for <8 mg/kg/day, p = 0.08). While 81 (17.2%) patients reported at least one adverse event (AE), only 11 (2.3%) and 3 (0.6%) had treatment-related AEs and serious AEs, respectively. Separate microbiologic findings from Leipzig University Hospital demonstrate small proportions of Enterococcus faecium isolates with daptomycin minimum inhibitory concentrations = 4 mg/L (4%) or ≥8 mg/L (0.8%), which are regarded as non-susceptible.ConclusionFor enterococcal infections, daptomycin appears to be an effective and well-tolerated treatment option, exhibiting highest clinical success rates at higher doses.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-015-0072-z) contains supplementary material, which is available to authorized users.

Pyocyanin induced in vitro oxidative damage and its toxicity level in human, fish and insect cell lines for its selective biological applications.

Pyocyanin is a redox active phenazine pigment produced by Pseudomonas aeruginosa, with broad antibiotic activity having pharmacological, aquaculture, agriculture and industrial applications. In the present work cytotoxicity induced by pyocyanin is demonstrated in a human embryonic lung epithelial cell line (L-132), a rainbow trout gonad cell line (RTG-2) and a Spodoptera frugiperda pupal ovarian cell line (Sf9). For toxicity evaluation, cellular morphology, mitochondrial function (XTT), membrane leakage of lactate dehydrogenase, neutral red uptake, affinity of electrostatic binding of protein with sulforhodamine B dyes, glucose metabolism, and reactive oxygen species, were assessed. Results showed that higher pyocyanin concentration is required for eliciting cytotoxicity in L-132, RTG-2 and Sf9. The microscopic studies demonstrated that the cell lines exposed to pyocyanin at higher concentrations alone showed morphological changes such as clumping and necrosis. Among the three cell lines L-132 showed the highest response to pyocyanin than the others. In short, pyocyanin application at concentrations ranging from 5 to 10mgl(-1) were not having any pathological effect in eukaryotic systems and can be used as drug of choice in aquaculture against vibrios in lieu of conventional antibiotics and as biocontrol agent against fungal and bacterial pathogens in agriculture. This is besides its industrial and pharmacological applications.

Synthesis and Antibacterial Activities of 5‐Hydroxy‐4‐amino‐2(5H)‐furanones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Chimeric Streptogramin-Tyrocidine Antibiotics that Overcome Streptogramin Resistance

Streptogramin antibiotics are comprised of two distinct chemical components: the type A polyketides and the type B cyclic depsipeptides. Clinical resistance to the type B streptogramins can occur via enzymatic degradation catalyzed by the lyase Vgb or by target modification through the action of Erm ribosomal RNA methyltransferases. We have prepared through chemical and chemo-enzymatic approaches a series of chimeric antibiotics composed of elements of type B streptogramins and the membrane-active antibiotic tyrocidine that evade these resistance mechanisms. These new compounds show broad antibiotic activity against gram-positive bacteria including a number of important pathogens, and chimeras appear to function by a mechanism that is distinct from their parent antibiotics. These results allow for the development of a brand new class of antibiotics with the ability to evade type B streptogramin-resistance mechanisms.

Synthesis and antibacterial activities of 5-hydroxy-4-amino-2(5 H)-furanones

Starting from the mucohalogen acids 1a and b 5-hydroxy-2(5 H)-furanones 2a– h have been prepared and tested. These novel 4-amino-5-hydroxy 2(5 H)-furananones have shown a broad antibiotic activity against Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 in the micromolar range. A one step synthesis from mucohalogen acids towards the antibacterials 2a– h was developed, in which the target was obtained from 1a and b under reflux in toluene in presence of a catalytic amount of sulfuric acid. The derivatives 2b and c displayed a MIC and MBC of 4/8 μg/ml, against Staphylococcus aureus with a selectivity towards the resistant strains.

Production of an isonitrile antibiotic by an UV-induced mutant of Trichoderma harzianum

Production of the antibiotic, homothallin II, by a UV-induced mutant strain of Trichoderma harzianum is reported, the wild-type parent of which was not an isonitrile antibiotic-producer. The compound has broad antibiotic activity against Oomycete, Ascomycete and Basidiomycete fungi, and both Gram-positive and -negative bacteria. The significance of the induction of homothallin II is discussed.

Bu-2470, a new peptide antibiotic complex. I. Production, isolation and properties of Bu-2470 A, B1 and B2.

A strain of Bacillus circulans produced a complex of basic peptide antibiotics designated Bu-2470, which was found to contain four active components, A, B1, B2a and B2b. Bu-2470 A specifically inhibited various Pseudomonas species including P. aeruginosa, P. maltophilia and P. putida, but otherwise its antibacterial spectrum was limited to certain Gram-negative organisms. Bu-2470 B1 and B2 (B2a + B2b) showed broad antibiotic activity against Gram-positive and Gram-negative bacteria including Pseudomonas species. The physicochemical and biological properties of Bu-2470 B1 and B2 are very similar to those of the octapeptin group of antibiotics.