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The swift increase in antimicrobial resistance across the world presents a significant challenge, further raised by insufficient advancement in the design of new antimicrobial agents. Over the past two decades, a variety of sources has been investigated for generating new antimicrobials. Recently, antimicrobial polymers (APs) have emerged as multifaceted agents, displaying effectiveness against a range of pathogens such as bacteria, fungi, and viruses. Their notable biocompatibility, efficiency, multifunctionality, and ease of modification make them a focal point of antimicrobial research. APs are particularly valued for their structural versatility, which allows for the integration of antimicrobial functional groups. Polymer functionalization does not only enhance or introduce antimicrobial properties but also maintains high levels of biocompatibility. This review reveals broad antimicrobial breadth of APs, which can be potentially used in antiseptics, food packaging, and in biomedical sector, as e.g. medical implants' coatings. In laboratory settings, APs have shown promising therapeutic effects, however there remains an urgent need for computational biology to fully understand their antimicrobial behaviour and stability. Recombinant biotechnological approaches are essential for facilitating the production of APs and require industrial collaboration to effectively optimize and scale up these production processes. [ABSTRACT FROM AUTHOR]

The urgent global health challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) infections demands effective solutions. Antimicrobial peptides (AMPs) represent promising tools of research of new antibacterial agents and LyeTx I mn∆K, a short synthetic peptide based on the Lycosa erythrognatha spider venom, is a good representative. This study focused on analyzing the antimicrobial activities of LyeTx I mn∆K, including minimum inhibitory and bactericidal concentrations, synergy and resensitization assays, lysis activity, the effect on biofilm, and the bacterial death curve in MRSA. Additionally, its characterization was conducted through isothermal titration calorimetry, dynamic light scattering, calcein release, and finally, efficacy in a mice wound model. The peptide demonstrates remarkable efficacy against planktonic cells (MIC 8–16 µM) and biofilms (>30% of inhibition) of MRSA, and outperforms vancomycin in terms of rapid bactericidal action and anti-biofilm effects. The mechanism involves significant membrane damage. Interactions with bacterial model membranes, including those with lysylphosphatidylglycerol (LysylPOPG) modifications, highlight the versatility and selectivity of this compound. Also, the peptide has the ability to sensitize resistant bacteria to conventional antibiotics, showing potential for combinatory therapy. Furthermore, using an in vivo model, this study showed that a formulated gel containing the peptide proved superior to vancomycin in treating MRSA-induced wounds in mice. Together, the results highlight LyeTx I mnΔK as a promising prototype for the development of effective therapeutic strategies against superficial MRSA infections. [ABSTRACT FROM AUTHOR]

The jelleine family is a group of four peptides (jelleines I–IV) originally isolated from the royal jelly of honey bee (Apis mellifera), but later detected in some honey samples. These oligopeptides are composed of 8–9 amino acid residues, positively charged (+2 to +3 at pH 7.2), including 38–50% of hydrophobic residues and a carboxamide C-terminus. Jelleines, generated by processing of the C-terminal region of major royal jelly proteins 1 (MRJP-1), play an important biological role in royal jelly conservation as well as in protecting bee larvae from potential pathogens. Therefore, these molecules present numerous benefits for human health, including therapeutic purposes as shown in preclinical studies. In this review, we aimed to evaluate the biological effects of jelleines in addition to characterising their toxicities and stabilities. Jelleines I–III have promising antimicrobial activity and low toxicity (LD50 > 1000 mg/Kg). However, jelleine-IV has not shown relevant biological potential. Jelleine-I, but not the other analogues, also has antiparasitic, healing, and pro-coagulant activities in addition to indirectly modulating tumor cell growth and controlling the inflammatory process. Although it is sensitive to hydrolysis by proteases, the addition of halogens increases the chemical stability of these molecules. Thus, these results suggest that jelleines, especially jelleine-I, are a potential target for the development of new, effective and safe therapeutic molecules for clinical use. [ABSTRACT FROM AUTHOR]

Infections caused by multidrug-resistant Acinetobacter baumannii (MDR-Ab) have become a public health emergency. Due to the small therapeutic arsenal available to treat these infections, health agencies have highlighted the importance of developing new antimicrobials against MDR-Ab. In this context, antimicrobial peptides (AMPs) stand out, and animal venoms are a rich source of these compounds. Here, we aimed to summarize the current knowledge on the use of animal venom-derived AMPs in the treatment of MDR-Ab infections in vivo. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The eight studies included in this review identified the antibacterial activity of eleven different AMPs against MDR-Ab. Most of the studied AMPs originated from arthropod venoms. In addition, all AMPs are positively charged and rich in lysine residues. In vivo assays showed that the use of these compounds reduces MDR-Ab-induced lethality and bacterial load in invasive (bacteremia and pneumonia) and superficial (wounds) infection models. Moreover, animal venom-derived AMPs have pleiotropic effects, such as pro-healing, anti-inflammatory, and antioxidant activities, that help treat infections. Animal venom-derived AMPs are a potential source of prototype molecules for the development of new therapeutic agents against MDR-Ab. [ABSTRACT FROM AUTHOR]

The increase in the incidence of fungal infections associated with the limited therapeutic arsenal available and the increasing rate of resistance of pathogenic fungi reinforce the need for research of new antifungal agents. Thus, this study aims to evaluate the antifungal activity of the peptide LyeTx I mnΔK, a shortened analogue of the natural peptide LyeTx I derived from spider venom, against Candida species. LyeTx I mnΔK showed potent activity against Candida spp. with minimum inhibitory concentration (MIC) and minimum fungicide concentration (MFC) between 4 and 32 µM. The peptide also completely inhibited the yeast-to-hypha transition (at 2 µM) and broke mature biofilms (67% reduction at 32 µM) of C. albicans. In addition, LyeTx I mnΔK did not induce resistance in C. albicans during 21 days of exposure. Therefore, the LyeTx I mnΔK is a promising prototype for the development of new antifungal agents. [ABSTRACT FROM AUTHOR]

Here, we demonstrated the in vitro and in vivo antibacterial and anti-biofilm activities of melittin, a peptide derived from honeybee venom, against uropathogenic Escherichia coli (UPEC) resistant to quinolones. The minimum inhibitory concentration (MIC) of melittin varied from 0.5 to 8 μM. The bactericidal effect was considered rapid and potent (ranging from 3.0 to 6.0 h after incubation) against a quinolone-resistant and Extended Spectrum Beta-lactamase (ESBL)-producing UPEC strain. Prior exposure to melittin did not reduce the MIC of the quinolones tested, but it decreased the MIC of ceftizoxime by 8-fold due to its ability to form pores in the membrane. Furthermore, melittin disrupted mature biofilms (39.58% at 32 μM) and inhibited the adhesion of this uropathogen to the surfaces of urethral catheter. These results show that melittin is a promising molecule that can be incorporated into invasive urethral medical devices to prevent urinary infections caused by multidrug-resistant UPECs. [ABSTRACT FROM AUTHOR]

The expression of virulence factors, such as biofilm formation, in association with the acquisition of resistance to multiple drugs, has evidenced the need for new and effective antimicrobial agents against Staphylococcus aureus. The evaluation of the pharmacological properties of plant-derived compounds is a promising alternative to the development of new antimicrobials. In this study, we aimed to evaluate the antibacterial, antibiofilm, and the synergistic and cytotoxic effects of netzahualcoyonol isolated from Salacia multiflora (Lam.) DC. roots. Netzahualcoyonol presented bacteriostatic (1.56–25.0 µg/mL) and bactericidal (25.0–400.0 µg/mL) effects against Gram-positive bacteria, disrupted the biofilm of S. aureus, and presented a synergistic effect after its combination with β-lactams and aminoglycosides. The low cytotoxicity of netzahualcoyonol (Selectivity Index (SI) for S. aureus (2.56), S. saprophyticus (20.56), and Bacillus subtilis (1.28)) suggests a good security profile. Taken together, these results show that netzahualcoyonol is promising for the development of a new effective antibacterial agent. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) infections are associated with severe neurological complications and are a global public health concern. There are no approved vaccines or antiviral drugs to inhibit ZIKV replication. NS2B‐NS3 protease (NS2B‐NS3 pro), which is essential for viral replication, is a promising molecular target for anti‐ZIKV drugs. We conducted a systematic review to identify compounds with promising effects against ZIKV; we discussed their pharmacodynamic and pharmacophoric characteristics. The online search, performed using the PubMed/MEDLINE and SCOPUS databases, yielded 56 articles; seven relevant studies that reported nine promising compounds with inhibitory activity against ZIKV NS2B‐NS3 pro were selected. Of these, five (niclosamide, nitazoxanide, bromocriptine, temoporfin, and novobiocin) are currently available on the market and have been tested for off‐label use against ZIKV. The 50% inhibitory concentration values of these compounds for the inhibition of NS2B‐NS3 pro ranged at 0.38–21.6 µM; most compounds exhibited noncompetitive inhibition (66%). All compounds that could inhibit the NS2B‐NS3 pro complex showed potent in vitro anti‐ZIKV activity with a 50% effective concentration ranging 0.024–50 µM. The 50% cytotoxic concentration of the compounds assayed using A549, Vero, and WRL‐69 cell lines ranged at 0.6–1388.02 µM and the selectivity index was 3.07–1698. This review summarizes the most promising antiviral agents against ZIKV that have inhibitory activity against viral proteases. [ABSTRACT FROM AUTHOR]

Viral infections of the lower respiratory tract are considered a public health problem. They affect millions of people worldwide, causing thousands of deaths, and are treated with expensive medicines, such as antivirals or palliative measures. In this study, we conducted a systematic review to describe the use of quercetin‐type flavonols against lower respiratory tract viruses and discussed the preclinical impact of this approach on different signs and clinical mechanisms of infection. The systematic review was performed in PubMed/MEDLINE, Scopus, Scielo, and Biblioteca Virtual de Saúde (BVS). After the database search, 11 relevant studies were identified as eligible. The analysis of these studies showed evidence of antiviral activity of quercetin‐type flavonols with significantly reduced mortality rate (M‐H = 0.19, 95% CI: 0.05 to 0.65, p‐value = 0.008) of infected animals and a reduction in the average viral load (IV = −1.93, 95% CI: −3.54 to −0.31, p‐value = 0.02). Additionally, quercetin and its derivatives reduced the amount of proinflammatory cytokines, chemokines, reactive oxygen species, mucus production, and airway resistance in animals infected with a respiratory virus. Overall, supplementation with quercetin‐type flavonols is a promising strategy for treating viral‐induced lower respiratory tract infections. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) is the most prevalent mosquito-borne viral pathogen and made the disease a major health concern worldwide. However, specific antiviral drugs against this arbovirose or vaccines are not yet available for treatment or prevention. Thus, here we aimed to study the antiviral activity of hydroethanolic extract, fraction ethyl acetate and subfractions of the leaves of Bauhinia holophylla (Fabaceae:Cercideae), a native plant of the Brazilian Cerrado, against DENV-2 by methylthiazolyldiphenyl-tetrazolium bromide (MTT) method in mammalian cells culture. As results, the hydroethanolic extract showed the most potent effect, with an inhibitory concentration (IC50) of 3.2 μg mL−1 and selectivity index (SI) of 27.6, approximately 16-times higher anti-DENV-2 activity than of the ribavirin (IC50 52.8 μg mL−1). Our results showed in this study appointed that B. holophylla has a promising anti-dengue activity, which was associated mainly with the presence of flavonoids. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the overall frequency of epilepsy in children with congenital Zika syndrome (CZS) and describe the profile of seizures and the response rate to anti‐epileptic treatment in this group of patients. Methods: A systematic review and meta‐analysis were conducted following the Cochrane Handbook and preferred reporting items for systematic reviews and meta‐analyses (PRISMA) guidelines. PubMed/MEDLINE, Scopus, Cochrane Library, SciELO, and LILACS were searched until June 23, 2020. Observational studies that evaluated the frequency of epilepsy in children diagnosed with CZS according to international criteria were included in the study. Results: Fourteen studies evaluating 903 patients diagnosed with CZS were pooled in a meta‐analysis. All studies were conducted in Brazil, with reports published between 2016 and 2020, and included children diagnosed with CSZ from 0 to 40 months of age. The overall rate of epilepsy in children diagnosed with CZS was estimated at 60% (95% confidence interval [CI] 0.51‐0.68). The studies included in this review show that the frequency of epilepsy in patients with CSZ varies with age, with higher rates in older children. Epileptic spasms was the primary type of seizure observed in this group, followed by focal and generalized crisis. The response rate to anti‐epileptic drugs was considerably low, ranging from 20% of seizure control in the first year and 30% in the second year. Significance: Children with CZS presented a high cumulative incidence of epilepsy episodes with increased severity and a low response to anti‐epileptic therapy, which is associated with the extensive damage caused by the Zika virus on the cortical structures of patients. [ABSTRACT FROM AUTHOR]

We conducted a systematic review and meta-analysis to determine the rate of polymyxin resistance among Acinetobacter baumannii isolates causing infection in hospitalized patients around the world during the period of 2010–2019. The systematic review was performed on September 1, 2019, using PubMed/MEDLINE, Scopus, and Web of Science; studies published after January 1, 2010, were selected. The data were summarized in tables, critically analyzed, and treated statistically using the RStudio® Software with Meta package and Metaprop Command. After applying exclusion factors, 41 relevant studies were selected from 969 articles identified on literature search. The overall rate of polymyxin-resistant A. baumannii (PRAB) related to hospitalized patients was estimated to be 13% (95% CI, 0.06–0.27), where a higher rate was observed in America (29%; 95% CI, 0.12–0.55), followed by Europe (13%; 95% CI, 0.02–0.52), and Asia (10%; 95% CI, 0.02–0.32). The extensive use of polymyxins on veterinary to control bacterial infection and growth promotion, as well as the resurgence in prescription and use of polymyxins in the clinics against carbapenem-resistant gram-negative bacteria, may have contributed to the increased incidence of PRAB. The findings of this meta-analysis revealed that the rate of PRAB recovered from hospitalized patients is distinctively high. Thus, action needs to be taken to develop strategies to combat the clinical incidence of PRAB-induced hospital infections. [ABSTRACT FROM AUTHOR]

The chemical composition and the phytotoxicity potential of the essential oil from leaves of Unonopsis guatterioides (A.DC.) R.E.Fr. (Annonaceae) was investigated. Gas chromatography/mass spectrometry analyses revealed 16 constituents representing 99.50% of the total essential oil, composed mainly of sesquiterpenes. α-copaene, bicyclogermacrene and trans-caryophyllene were the major components (15.7% each), followed by α-humullene, allo-aromadendrene and (+)-spathulenol (9.0, 8.4 and 7.3%, respectively). The essential oil inhibited seed germination and growth in both monocotyledon (Allium cepa) and dicotyledon (Lactuca sativa) models, pointing to a promising application of this oil obtained from the leaves of U. guatterioides as a new bioherbicide. [ABSTRACT FROM AUTHOR]

Benzoxazinoids (BXs), alkaloids frequently found in Gramineae species, are natural defensives that can potentially be exploited to the development of novel antimicrobial agents. Here, BXs analogs were synthesized from 2-nitrophenol (benzoxazinone series) and 3-hydroxy-2-nitropyridine (pyridoxazinone series) and tested against fungal and bacteria of medical interest. The starting materials were submitted to adequate nucleophilic substitution in order to functionalize of analogs, followed by a reductive cyclization catalyzed by palladium on carbon. Next, the biological assays showed that pyridoxazinone serie has a good antibacterial activity, especially against Enterococcus faecalis (Minimum inhibitory concentration—MIC: 7.8-15.6 μg.mL−1) and Acinetobacter baumannii (MIC 31.25-125 μg.mL−1). Antifungal activity, in turn, was related to compound 2e which showed a MIC of 62.5 μg.mL−1 against Candida albicans, Candida glabrata, and Candida tropicalis. All analogs complied with Lipinski's rules and were predicted to have a low toxicity. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is an opportunistic pathogen associated with nosocomial and community infections of great clinical relevance. Its ability to rapidly develop resistance to antimicrobials, especially carbapenems, has re-boosted the prescription and use of polymyxins. However, the emergence of strains resistant to these antimicrobials is becoming a critical issue in several regions of the world because very few of currently available antibiotics are effective in these cases. This review summarizes the most up-to-date knowledge about chromosomally encoded and plasmid-mediated polymyxins resistance in A. baumannii. Different mechanisms are employed by A. baumannii to overcome the antibacterial effects of polymyxins. Modification of the outer membrane through phosphoethanolamine addition, loss of lipopolysaccharide, symmetric rupture, metabolic changes affecting osmoprotective amino acids, and overexpression of efflux pumps are involved in this process. Several genetic elements modulate these mechanisms, but only three of them have been described so far in A. baumannii clinical isolates such as mutations in pmrCAB, lpxACD, and lpsB. Elucidation of genotypic profiles and resistance mechanisms are necessary for control and fight against resistance to polymyxins in A. baumannii, thereby protecting this class for future treatment. [ABSTRACT FROM AUTHOR]

Ethanol extract and fractions obtained from fresh and dry aerial parts ofLippia albawere examined in order to determine their phytochemical composition, antioxidant capacity and antibacterial activities. The ethanol extracts and fractions exhibited an antioxidant effect by the DPPH assay, especially samples of fresh plant. HPLC analysis of the ethyl acetate fractions identified the presence of phenolic acids and flavonoids. The ethanol extract and fractions showed activity against reference and multidrug-resistant strains ofStaphylococcus aureusandEnterococcus faecalis(MIC range 2000–250 μg/mL). The hexane and dichloromethane fractions of fresh plant showed better activity against reference strains ofEscherichia coli(MIC of 250 and 125 μg/mL, respectively), but all extracts and fractions were less active against multidrug-resistant strains of all the Gram-negative species evaluated. The results showed that the extract and fractions ofL albaaerial parts showed antibacterial activity, even against multidrug-resistant Gram-positive bacteria, and antioxidant effect (DPPH assay). [ABSTRACT FROM PUBLISHER]

Intra-abdominal candidiasis (IAC) occurs due to the direct inoculation of Candida into the sterile peritoneal cavity or leakage of the gastrointestinal tract. An important difference between the two forms of the disease is the presence of fecal material, which is exclusive to the latter condition. However, the influence of fecal material on the prognosis of IAC is still poorly understood. Furthermore, methodologies that use the quantification of fungal load by culture methods have low sensitivity, as they do not adequately show the precocity of the infectious process. Here, we developed a new method to evaluate the aspects of the pathophysiology of IAC, mainly the influence of fecal material on the prognosis of infection, by using C. albicans radiolabeled with technetium-99 m (99 mTc). C. albicans was successfully radiolabeled with 99 mTc (18.5 MBq) using dihydrate stannous chloride (100 µM) as a reducing agent. This binding was stable for 72 h. Viability, yeast-to-hyphae transition, morphology, and antifungal susceptibility were not altered by radiolabeling C. albicans with 99 mTc. The biomass and the fungal load of 99 mTc- C. albicans biofilms were reduced compared to the C. albicans non-radiolabeled after 72 h and 48 h of incubation, respectively. In the IAC model, the fungal load in the biodistribution of 99 mTc- C. albicans and culture assays was higher in animals receiving fungal inoculum without fecal material, suggesting that the presence of this component reduces the invasiveness of the pathogen. • Candida albicans was efficiently labeling with technetium-99 m (99 mTc). • Viability, yeast-to-hyphae transition, morphology, and antifungal susceptibility were not altered in Tc- C. albicans • Fecal material reduces invasiveness of C. albicans in a murine model of intra-abdominal candidiasis. [ABSTRACT FROM AUTHOR]

Summary: Dengue virus is known to modulate host cell lipid metabolism in order to promote efficient viral replication. Recent studies have focused on circulating lipids as potential biomarkers of dengue severity; however, the results obtained so far lack the consistency to establish a definite relationship between the two. Therefore, in the present study, we investigated serum lipids as potential biomarkers of dengue severity by conducting a meta‐analysis of the currently available clinical data. Nine studies that evaluated 1,953 patients were included in the review, many of which were cross‐sectional (44.4%) and conducted in Asian countries (55.5%). These studies observed the presence of lipids in serum samples (77%) of patients in the acute phase of the disease (88.8%). Circulating total‐cholesterol (P = .001) and LDL (P = .001) levels, but not HDL (P = .07), VLDL (P = .9) and triglyceride (P = .57) levels, were inversely and significantly correlated with dengue severity. Total cholesterol (P ≤ .001) and LDL (P = .001) were also useful in determining the risk of hypovolemic shock in patients with severe dengue. Subgroup analysis showed that factors, such as design (cross‐sectional vs cohort), racial‐ethnic differences (Asian vs Latin Americans), and age range (children vs adult) influenced the correlation and also contributed to the high level of heterogeneity in the studies. Our meta‐analysis demonstrates that total‐cholesterol and LDL‐cholesterol levels should be explored as routine laboratory markers for dengue severity, as they will help in employing an appropriate patient therapy, and thus optimize the use of available resources. [ABSTRACT FROM AUTHOR]

Apitherapy is a branch of traditional medicine that uses bee products to manage numerous diseases. In this context, the antiherpetic effect of these bee products has been demonstrated in some studies with some controversial results. Thus, we conducted a systematic review and meta-analysis to compare the effectiveness of honey and propolis with acyclovir, the reference drug, in the treatment of cold sores and genital herpes. The selection of eligible studies was conducted through the search in Pubmed/MEDLINE, Scopus, Cochrane Library, LILACS, and Electronic Scientific Library. The search yielded 147 articles, of which nine were considered eligible for analysis. The analysis of these studies showed that the healing property of propolis is superior to that obtained for acyclovir (95% CI: 2.70 to 8.25; p = 0.0001). Furthermore, honey also presented a better healing effect than acyclovir against Herpes simplex virus-induced wounds (95% CI: 3.58 to −0.19; p = 0.03), inducing complete re-epithelization of herpetic lesions after 8 days, while for acyclovir, the healing time average was 9 days. It also provoked a similar reduction of pain caused by herpetic compared to acyclovir (95% CI: 2.27 to −0.42; p = 0.18). Overall, these results confirm the use of honey and propolis as potent antiherpetic agents. [Display omitted] • Honey and propolis are potent antiviral agents against oral and genital herpes. • Honey presented a better healing effect than acyclovir against HSV-induced wounds. • Honey induced complete re-epithelization of herpetic lesions after 8 days of treatment (in mean). • The reduction of pain caused by herpetic lesions by honey is equivalent to acyclovir. • Healing property of propolis is superior to that obtained for acyclovir in herpetic lesions. [ABSTRACT FROM AUTHOR]

We conducted a systematic review and meta-analysis to determine the rate of contamination in bovine meat and meat products with Shiga toxin-producing Escherichia coli (STEC) in Brazil over the last fifteen years. Data were obtained from online databases in February 2020, and 25 papers were selected from 1036 articles identified in the literature search and 13 articles from gray literature, totaling 4286 samples analyzed. The overall rate of STEC was estimated to be 1% in Brazil. The highest rate (9%) was observed in Mato Grosso, followed by Rio Grande do Sul (1%), Goiás (1%), and São Paulo (1%). Regarding the sample type analyzed, hot carcasses had the highest rate (8%) of positive samples for STEC, followed by cold carcasses (2%) and beef samples (1%). As the available data were concentrated in the São Paulo state, the findings of this meta-analysis reveal the need for further studies in Brazil to allow better risk assessment and prevention of human STEC infections. • Meta-analysis was conducted to estimate the prevalence of STEC in Brazilian meats. • The studies were concentrated in the southeastern region, mainly in São Paulo state. • A great heterogeneity of contamination rate was observed among studies and regions. • The highest rate of contamination with STEC was observed in Mato Grosso state. • Hot carcasses had the highest rate of contamination among the sample types analyzed. [ABSTRACT FROM AUTHOR]