Anti-Planktonic and Anti-Biofilm Properties of Pentacyclic Triterpenes—Asiatic Acid and Ursolic Acid as Promising Antibacterial Future Pharmaceuticals

Due to the ever-increasing number of multidrug-resistant bacteria, research concerning plant-derived compounds with antimicrobial mechanisms of action has been conducted. Pentacyclic triterpenes, which have a broad spectrum of medicinal properties, are one of such groups. Asiatic acid (AA) and ursolic acid (UA), which belong to this group, exhibit diverse biological activities that include antioxidant, anti-inflammatory, diuretic, and immunostimulatory. Some of these articles usually contain only a short section describing the antibacterial effects of AA or UA. Therefore, our review article aims to provide the reader with a broader understanding of the activity of these acids against pathogenic bacteria. The bacteria in the human body can live in the planktonic form and create a biofilm structure. Therefore, we found it valuable to present the action of AA and UA on both planktonic and biofilm cultures. The article also presents mechanisms of the biological activity of these substances against microorganisms.

Impact of Healthcare-Associated Infections Connected to Medical Devices—An Update

Healthcare-associated infections (HAIs) are caused by nosocomial pathogens. HAIs have an immense impact not only on developing countries but also on highly developed parts of world. They are predominantly device-associated infections that are caused by the planktonic form of microorganisms as well as those organized in biofilms. This review elucidates the impact of HAIs, focusing on device-associated infections such as central line-associated bloodstream infection including catheter infection, catheter-associated urinary tract infection, ventilator-associated pneumonia, and surgical site infections. The most relevant microorganisms are mentioned in terms of their frequency of infection on medical devices. Standard care bundles, conventional therapy, and novel approaches against device-associated infections are briefly mentioned as well. This review concisely summarizes relevant and up-to-date information on HAIs and HAI-associated microorganisms and also provides a description of several useful approaches for tackling HAIs.

Halogen-Furan-2(5H)-One Derivatives Decrease Biofilm Production in Pseudomonas aeruginosa.

Clinical evidence has shown that bacterial infections are more difficult to eradicate when form-ing a biofilm aggregate than when are produced by bacteria in planktonic form. Therefore, com-pounds that inhibit biofilm formation could be used against severe infections. It has been re-ported that bromo 2-(5H) furanones inhibited biofilm formation by their anti-quorum sensing properties. To determine if the 2-(5H) furanone moiety is essential to induce inhibition of biofilm formation, we evaluated ten halogen 2-(5H) furanones derivates previously synthesized. Besides evaluating the inhibition of biofilm formation, we assessed pyocyanin production, swarming motility, and transcription of essential QS genes: rsaL, rhlA, pqsA and phz1 genes. Our results showed that although three bromo-furan-2(5H)-one-type derivatives (A1-A3) and two bromo-4-(phenylamino)-furan-2(5H)-one-type compounds (B2 and B6) inhibited the biofilm formation in both P. aeruginosa PA14 (reference) and PA64 (drug-resistant) strains only the furanones A1-A3 were efficient to inhibit QSS.

Biofilm Formation Is Crucial for Efficient Copper Bioleaching From Bornite Under Mesophilic Conditions: Unveiling the Lifestyle and Catalytic Role of Sulfur-Oxidizing Bacteria

Biofilm formation within the process of bioleaching of copper sulfides is a relevant aspect of iron- and sulfur-oxidizing acidophilic microorganisms as it represents their lifestyle in the actual heap/dump mining industry. Here, we used biofilm flow cell chambers to establish laminar regimes and compare them with turbulent conditions to evaluate biofilm formation and mineralogic dynamics through QEMSCAN and SEM-EDS during bioleaching of primary copper sulfide minerals at 30°C. We found that laminar regimes triggered the buildup of biofilm using Leptospirillum spp. and Acidithiobacillus thiooxidans (inoculation ratio 3:1) at a cell concentration of 106 cells/g mineral on bornite (Cu5FeS4) but not for chalcopyrite (CuFeS2). Conversely, biofilm did not occur on any of the tested minerals under turbulent conditions. Inoculating the bacterial community with ferric iron (Fe3+) under shaking conditions resulted in rapid copper recovery from bornite, leaching 40% of the Cu content after 10 days of cultivation. The addition of ferrous iron (Fe2+) instead promoted Cu recovery of 30% at day 48, clearly delaying the leaching process. More efficiently, the biofilm-forming laminar regime almost doubled the leached copper amount (54%) after 32 days. In-depth inspection of the microbiologic dynamics showed that bacteria developing biofilm on the surface of bornite corresponded mainly to At. Thiooxidans, while Leptospirillum spp. were detected in planktonic form, highlighting the role of biofilm buildup as a means for the bioleaching of primary sulfides. We finally propose a mechanism for bornite bioleaching during biofilm formation where sulfur regeneration to sulfuric acid by the sulfur-oxidizing microorganisms is crucial to prevent iron precipitation for efficient copper recovery.

Established Gardnerella biofilms can survive metronidazole treatment by reducing metabolic activity

Gardnerella spp., a hallmark of bacterial vaginosis, can form biofilm and it has been suggested that failure of antibiotic treatment of bacterial vaginosis and recurrent vaginosis are linked to its ability to form biofilm. Here, we tested the hypothesis that biofilm formation provides protection from the effects of metronidazole. We performed a broth microdilution assay to measure the minimum inhibitory concentration (MIC) of metronidazole for thirty-five Gardnerella isolates in two different growth media: one medium in which Gardnerella spp. grow primarily as biofilm and the other medium in which Gardnerella spp. grow primarily in planktonic form. The MIC of Gardnerella isolates observed in the two conditions were highly correlated (R2= 0.69, p <0.001) and 27/35 isolates had no difference in MIC between the two growth modes. When established biofilms were treated with metronidazole, live Gardnerella could be recovered following treatment in most cases (7/9 isolates tested). Metabolic activity of established biofilms of thirty-one isolates with and without metronidazole treatment was measured using a resazurin assay. Most (27/31) isolates showed reduced metabolic activity following treatment with μ128 g/ml of metronidazole relative to untreated controls. The amount of biofilm produced by Gardnerella isolates was not enhanced by sub-inhibitory concentrations of metronidazole and scanning electron microscopy revealed no architectural differences between treated and untreated biofilms. Our results suggest that Gardnerella spp. growing in established biofilms reduce metabolic activity as a mechanism of protection from the bactericidal effects of metronidazole.

Antimicrobial Activity of MgB2 Powders Produced via Reactive Liquid Infiltration Method

We report for the first time on the antimicrobial activity of MgB2 powders produced via the Reactive Liquid Infiltration (RLI) process. Samples with MgB2 wt.% ranging from 2% to 99% were obtained and characterized, observing different levels of grain aggregation and of impurity phases. Their antimicrobial activity was tested against Staphylococcus aureus ATCC BAA 1026, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, and Candida albicans ATCC 10231. A general correlation is observed between the antibacterial activity and the MgB2 wt.%, but the sample microstructure also appears to be very important. RLI-MgB2 powders show better performances compared to commercial powders against microbial strains in the planktonic form, and their activity against biofilms is also very similar.

Antibiotic Resistance and Biofilm Production Capacity in Clostridioides difficile

BackgroundClostridioides difficile (C. difficile) is one of the primary pathogens responsible for infectious diarrhea. Antibiotic treatment failure, occurring in about 30% of patients, and elevated rates of antibiotic resistance pose a major challenge for therapy. Reinfection often occurs by isolates that produce biofilm, a protective barrier impermeable to antibiotics. We explored the association between antibiotic resistance (in planktonic form) and biofilm-production in 123 C. difficile clinical isolates.ResultsOverall, 66 (53.6%) out of 123 isolates produced a biofilm, with most of them being either a strong (44%) or moderate (34.8%) biofilm producers. When compared to susceptible isolates, a statistically higher percentage of isolates with reduced susceptibility to metronidazole or vancomycin were biofilm producers (p &lt; 0.0001, for both antibiotics). Biofilm production intensity was higher among tolerant isolates; 53.1% of the metronidazole-susceptible isolates were not able to produce biofilms, and only 12.5% were strong biofilm-producers. In contrast, 63% of the isolates with reduced susceptibility had a strong biofilm-production capability, while 22.2% were non-producers. Among the vancomycin-susceptible isolates, 51% were unable to produce biofilms, while all the isolates with reduced vancomycin susceptibility were biofilm-producers. Additionally, strong biofilm production capacity was more common among the isolates with reduced vancomycin susceptibility, compared to susceptible isolates (72.7% vs. 18.8%, respectively). The distribution of biofilm capacity groups was statistically different between different Sequence-types (ST) strains (p =0.001). For example, while most of ST2 (66.7%), ST13 (60%), ST42 (80%) isolates were non-producers, most (75%) ST6 isolates were moderate producers and most of ST104 (57.1%) were strong producers.ConclusionsOur results suggest an association between reduced antibiotic susceptibility and biofilm production capacity. This finding reinforces the importance of antibiotic susceptibility testing, mainly in recurrence infections that may be induced by a strain that is both antibiotic tolerant and biofilm producer. Better adjustment of treatment in such cases may reduce recurrences rates and complications. The link of biofilm production and ST should be further validated; if ST can indicate on isolate virulence, then in the future, when strain typing methods will be more available to laboratories, ST determination may aid in indecision between supportive vs. aggressive treatment.

EFFECT OF Staphylococcus epidermidis ON Pseudomonas aeruginosa BIOFILM IN MIXED-SPECIES CULTURE

Staphylococcus epidermidis and Pseudomonas aeruginosa, are clinically relevant pathogens that often produce biofilms. To investigate the co-survivability of S. epidermidis and P. aeruginosa in mixed cultures biofilm and planktonic form, it is important to understand more about the interspecies interaction of both species. The interspecies interaction was analyzed using streak and drop agar plate assay, cell viability assay (CFU), spectrophotometry-based method, and microscopic analysis. The findings suggest that both cells and supernatant of P. aeruginosa inhibit the planktonic growth of S. epidermidis. The cell viability result shows that PAO1 biofilm cells were decreased by 88%, and SE biofilm cells were increased by 75% concerning their control. Opposite to the P. aeruginosa, the S. epidermidis biofilm and EPS matrix were found to increase in mixed culture biofilm, which was further confirmed by microscopic analysis. In contrast, differential agar media result shows that the reduction in the biofilm (CFU/ml) of P. aeruginosa is independent of S. epidermidis cells concentration. Finally, the effect of the supernatant on biofilm was investigated, and it found that S. epidermidis biofilm was enhanced while P. aeruginosa biofilm was reduced in the presence of partner bacterial supernatant, which indicated that S. epidermidis in biofilm mode could hinder the biofilm formation of P. aeruginosa. The outcomes show that the culture supernatant of S. epidermidis can be used to prevent P. aeruginosa associated biofilm infections.

Antimicrobial Peptides Derived From Insects Offer a Novel Therapeutic Option to Combat Biofilm: A Systematic Review

Biofilms form a complex layer with defined structures, that attach on biotic or abiotic surfaces, are tough to eradicate and tend to cause some resistance against most antibiotics. Several studies confirmed that biofilm-producing bacteria exhibit higher resistance compared to the planktonic form of the same species. Antibiotic resistance factors are well understood in planktonic bacteria which is not so in case of biofilm producing forms. This may be due to the lack of available drugs with known resistance mechanisms for biofilms. Existing antibiotics cannot eradicate most biofilms, especially of ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). Insects produce complex and diverse set of chemicals for survival and defense. Antimicrobial peptides (AMPs), produced by most insects, generally have a broad spectrum of activity and the potential to bypass the resistance mechanisms of classical antibiotics. Besides, AMPs may well act synergistically with classical antibiotics for a double-pronged attack on infections. Thus, AMPs could be promising alternatives to overcome medically important biofilms, decrease the possibility of acquired resistance and treatment of multidrug-resistant pathogens including ESKAPE. The present review focuses on insect-derived AMPs with special reference to anti-biofilm-based strategies. It covers the AMP composition, pathways and mechanisms of action, the formation of biofilms, impact of biofilms on human diseases, current strategies as well as therapeutic options to combat biofilm with antimicrobial peptides from insects. In addition, the review also illustrates the importance of bioinformatics tools and molecular docking studies to boost the importance of select bioactive peptides those can be developed as drugs, as well as suggestions for further basic and clinical research.

Antibiotic Resistance in the Alternative Lifestyles of Campylobacter jejuni

Campylobacter jejuni is the main pathogen identified in cases of foodborne gastroenteritis worldwide. Its importance in poultry production and public health is highlighted due to the growing antimicrobial resistance. Our study comparatively investigated the effect of five different classes of antimicrobials on the planktonic and biofilm forms of 35 strains of C. jejuni with high phylogenetic distinction in 30 of them. In the planktonic form, the existence of susceptible strains to colistin (7/35 – 20%) and resistance to meropenem (3/35 – 8.6%) represent a novelty in strains evaluated in Brazil. In biofilms formed with the addition of chicken juice, the number of resistant strains was significantly higher for colistin, erythromycin and meropenem (100%), but the susceptibility to tetracycline was shown as a control strategy for specific cases. High concentrations (1,060 ± 172.1mg/L) of antibiotics were necessary to control the biofilm structure in susceptible strains in the planktonic form, which is consistent with the high biomass produced in these strains. Stainless steel and polyurethane were the most (BFI=2.1) and least (BFI=1.6) favorable surfaces for the production of biomass treated with antimicrobials. It is concluded that the antimicrobial action was detected for all tested drugs in planktonic form. In sessile forms, the biomass production was intensified, except for tetracycline, which showed an antibiofilm effect.