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Competing Interests: Conflicts of interest None.

We compared the ability of one emergent (Sagittaria montevidensis), two floating (Salvinia minima and Lemna gibba), and one heterophyllous species (Myriophyllum aquaticum) to simultaneously remove sulfamethoxazole, sulfadiazine, ciprofloxacin, enrofloxacin, norfloxacin, levofloxacin, oxytetracycline, tetracycline, doxycycline, azithromycin, amoxicillin, and meropenem from wastewater in a mesocosm-scale constructed wetland over 28 days. Antibiotic concentrations in plants and effluent were analyzed using an LC-MS/MS to assess the removal rates and phytoremediation capacities. M. aquaticum did not effectively mitigate contamination due to poor tolerance and survival in effluent conditions. S. minima and L. gibba demonstrated superior efficiency, reducing the antibiotic concentrations to undetectable levels within 14 days, while S. montevidensis achieved this result by day 28. Floating macrophytes emerge as the preferable choice for remediation of antibiotics compared to emergent and heterophyllous species. Antibiotics were detected in plant tissues at concentrations ranging from 0.32 to 29.32 ng g -1 fresh weight, highlighting macrophytes' ability to uptake and accumulate these contaminants. Conversely, non-planted systems exhibited a maximum removal rate of 65%, underscoring the persistence of these molecules in natural environments, even after the entire experimental period. Additionally, macrophytes improved effluent quality regardless of species by reducing total soluble solids and phosphate concentrations and mitigating ecotoxicological effects. This study underscores the potential of using macrophytes in wastewater treatment plants to enhance overall efficiency and prevent environmental contamination by antibiotics, thereby mitigating the harmful impact on biota and antibiotic resistance. Selecting appropriate plant species is crucial for successful phytoremediation in constructed wetlands, and actual implementation is essential to validate their effectiveness and practical applicability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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.

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 (LD 50 > 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.

Enrofloxacin (Enro) has been widely encountered in natural water sources, and that water is often used for irrigation in crop production systems. Due to its phytotoxicity and accumulation in plant tissues, the presence of Enro in water used for crop irrigation may represent economical and toxicological concerns. Here, we irrigated two ornamental plant species (Zantedeschia rehmannii Engl. and Spathiphyllum wallisii Regel.) with water artificially contaminated with the antimicrobial enrofloxacin (Enro; 0, 5, 10, 100, and 1000 μg L -1 ) to evaluate its effects on ornamental plant production, as well as its accumulation and distribution among different plant organs (roots, leaves, bulbs, and flower stems), and examined the economic and environmental safety of commercializing plants produced under conditions of pharmaceutical contamination. The presence of Enro in irrigation water was not found to disrupt plant growth (biomass) or flower production. Both species accumulated Enro, with its internal concentrations distributed as the following: roots > leaves > bulbs > flower stems. In addition to plant tolerance, the content of Enro in plant organs indicated that both Z. rehmannii and S. wallisii could be safety produced under Enro-contaminated conditions and would not significantly contribute to contaminant transfer. The high capacity of those plants to accumulate Enro in their tissues, associated with their tolerance to it, indicates them for use in Enro-phytoremediation programs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Phytoremediation has been a potential solution for the removal of pharmaceuticals from water. Here, we evaluated the toxicological safety of ciprofloxacin-contaminated water treated by 96 h with Salvinia molesta. The Neotropical catfish Rhamdia quelen was used as a model, and the potential of the phytoremediation technique for mitigating the drug accumulation in the fishes was also studied. Fish exposed to Cipro (1 and 10 µg·L -1 ) in untreated water showed toxic responses (alteration of hematological, genotoxicity, biochemical, and histopathological biomarkers) and accumulated Cipro in their muscles at concentrations high for human consumption (target hazardous quotient > 1). Fish exposed to water treated with S. molesta showed no toxic effect and no accumulation of Cipro in their tissues. This must be related to the fact that S. molesta removed up to 97% of Cipro from the water. The decrease in Cipro concentrations after water treatment with S. molesta not only prevented the toxic effects of Cipro on R. quelen fish but also prevented the antimicrobial accumulation in fish flesh, favouring safe consumption by humans. For the very first time, we showed the potential of phytoremediation as an efficiently nature-based solution to prevent environmental toxicological effects of antimicrobials to nontarget organisms such as fish and humans. The use of S. molesta for Cipro-removal from water is a green technology to be considered in the combat against antimicrobial resistance., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ciprofloxacin (Cipro) water contamination is a global concern, having reached disturbing concentrations and threatening the aquatic ecosystems. We investigated the physiological responses and Cipro-phytoremediation capacity of one floating (Salvinia molesta D.S. Mitchell) and one submerged (Egeria densa Planch.) species of aquatic macrophytes. The plants were exposed to increased concentrations of Cipro (0, 1, 10, and 100 µg.Cipro.L -1 ) in artificially contaminated water for 96 and 168 h. Although the antibiotic affected the activities of mitochondrial electron transport chain enzymes, the resulting increases in H 2 O 2 concentrations were not associated with oxidative damage or growth reductions, mainly due to the activation of antioxidant systems for both species. In addition to being tolerant to Cipro, after only 96 h, plants were able to reclaim more than 58% of that from the media. The phytoremediation capacity did not differ between the species, however, while S. molesta bioaccumulate, E. densa appears to metabolize Cipro in their tissues. Both macrophytes are indicated for Cipro-phytoremediation projects., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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.

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 m Tc). C. albicans was successfully radiolabeled with 99 m Tc (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 m Tc. The biomass and the fungal load of 99 m Tc-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 m Tc-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., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Arthropod-borne viruses (arboviruses), such as Zika virus (ZIKV), chikungunya virus (CHIKV), dengue virus (DENV), yellow fever virus (YFV), and West Nile virus (WNV), are pathogens of global importance. Therefore, there has been an increasing need for new drugs for the treatment of these viral infections. In this context, antimicrobial peptides (AMPs) obtained from animal venoms stand out as promising compounds because they exhibit strong antiviral activity against emerging arboviral pathogens. Thus, we systematically searched and critically analyzed in vitro and in vivo studies that evaluated the anti-arbovirus effect of peptide derivatives from toxins produced by vertebrates and invertebrates. Thirteen studies that evaluated the antiviral action of 10 peptides against arboviruses were included in this review. The peptides were derived from the venom of scorpions, spiders, wasps, snakes, sea snails, and frogs and were tested against DENV, ZIKV, YFV, WNV, and CHIKV. Despite the high structural variety of the peptides included in this study, their antiviral activity appears to be associated with the presence of positive charges, an excess of basic amino acids (mainly lysine), and a high isoelectric point (above 8). These peptides use different antiviral mechanisms, the most common of which is the inhibition of viral replication, release, entry, or fusion. Moreover, peptides with virucidal and cytoprotective (pre-treatment) effects were also identified. In conclusion, animal-venom-derived peptides stand out as a promising alternative in the search and development of prototype antivirals against arboviruses., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Staphylococcus aureus is a Gram-positive bacterium responsible for a wide variety of infectious diseases, and its methicillin-resistant isolates pose a serious worldwide public health risk. New drugs are urgently needed for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we evaluated the antibacterial activity of five 3-alkyl-pyridinic analogs against MRSA and, of these compounds, compound 6 showed promising antibacterial activity against Staphylococcus with minimum inhibitory concentration (MIC) ranging from 0.98 to 3.9 μgmL - ¹ . In addition, it exhibited a rapid bactericidal action, with complete elimination of MRSA after 6 h of incubation at 15.6 μgmL - ¹ . Compound 6 had the ability to damage the bacterial membrane and induce cell lysis and, due to its action on the membrane, showed low resistance induction potential in vitro. In the combination study, compound 6 revealed an additive effect (FICI = 1) with vancomycin and ofloxacin and ciprofloxacin (FICI = 0.75) against MRSA, reducing the effective concentration of this antibiotic two-fold. The anti-staphylococcal activity of compound 6 was stable in the presence of different concentrations of NaCl (50, 200, and 400 µM), trypsin ( 1:500, 1:250) and under a variety of pH values (4, 5, 6, and 8); however, its binding to plasmatic proteins (i.e., albumin) was substantial. The previous exposure of MRSA to the compound was able to reduce the formation of bacterial biofilm and reduce the biomass of mature biofilms. Compound 6 showed low selectivity in vitro for MRSA USA 300 when compared to eukaryotic cells (epithelial, fibroblast, and red blood cells)., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Vulvovaginal candidosis (VVC) is one of the most frequent causes of gynecological consultations. Therefore, the development of new antifungal therapies against VVC is relevant. In this context, the leaves of Fridericia chica (Bonpl.) L. G. Lohmann are considered a therapeutic alternative since they are traditionally used in VVC therapy. However, no scientific evidence has supported this use against fungal vaginal infections. Then, we aimed to characterize the antifungal effect of a hydroethanolic extract of F. chica leaves (HEFc) and evaluate the therapeutic potential of this extract in a VVC model. HEFc inhibited the growth of C. albicans (256-1,204 µg/mL) and C. krusei (512 µg/mL) in vitro. HEFc inhibited yeast-to-hypha transition in C. albicans and has a low ability to induce resistance in this species. Intravaginal use of the HEFc at 50 mg/mL causes mycological cure in animals with VVC after 6 days of treatment, similar to the effect observed for the commercial antifungal nystatin. These results support the traditional use of F. chica leaves as a topical therapeutic option to treat VVC., (Copyright © 2022 SFMM. Published by Elsevier Masson SAS. All rights reserved.)

Cryptococcus gattii, an environmental yeast isolated from plants, is one of the agents of cryptococcosis. Here, we aimed to develop a plant model to study C. gattii-plant interaction, since it is unclear how it affects the plant and the yeast. We tested three inoculation methods (scarification, infiltration, and abrasion) in three plant species: Arabidopsis thaliana, Nicotiana tabacum, and N. benthamiana. Cryptococcus gattii was able to grow in all three models, with a peak of yeast cell burden after 7 days, without any pathological effects. Furthermore, the fungal burden was reduced later, confirming that C. gattii is not a phytopathogen. Cryptococcus gattii proliferation was higher in N. benthamiana, which presented an increase in the hydrogen peroxide content, antioxidant system activity, and indoleacetic acid (IAA) production. Cryptococcus gattii colonies recovered from N. benthamiana presented lower ergosterol content, reduced capsule, and increased growth rate in vitro and inside macrophages. In vitro, IAA altered C. gattii morphology and susceptibility to antifungal drugs. We hypothesize that C. gattii can temporarily colonize plant living tissues, which can be a potential reservoir of yeast virulence, with further dissemination to the environment, birds, and mammals. In conclusion, N. benthamiana is suitable for studying C. gattii-plant interaction., (© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.)

Ethnopharmacological Relevance: 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., Aim of the Study: 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., Materials and Methods: The selection of eligible studies was conducted through the search in Pubmed/MEDLINE, Scopus, Cochrane Library, LILACS, and Electronic Scientific Library., Results: 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)., Conclusions: Overall, these results confirm the use of honey and propolis as potent antiherpetic agents., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., (© 2021 John Wiley & Sons Ltd.)

The emergence of antibiotic-resistant bacteria, especially carbapenem-resistant Acinetobacter baumannii (CRAB), together with relative stagnation in the development of effective antibiotics, has led to enormous health and economic problems. In this study, we aimed to describe the antibacterial spectrum of LyeTx I mnΔK, a short synthetic peptide based on LyeTx I from Lycosa erythrognatha venom, against CRAB. LyeTx I mnΔK showed considerable antibacterial activity against extensively resistant A. baumannii, with minimum inhibitory and bactericidal concentrations ranging from 1 to 16 µM and 2 to 32 µM, respectively. This peptide significantly increased the release of 260 nm-absorbing intracellular material from CRAB, suggesting bacteriolysis. LyeTx I mnΔK was shown to act synergistically with meropenem and colistin against CRAB. The cytotoxic concentration of LyeTx I mnΔK against Vero cells (CC 50  = 55.31 ± 5.00 µM) and its hemolytic activity (HC 50  = 77.07 ± 4.00 µM) were considerably low; however, its antibacterial activity was significantly reduced in the presence of human and animal serum and trypsin. Nevertheless, the inhalation of this peptide was effective in reducing pulmonary bacterial load in a mouse model of CRAB infection. Altogether, these results demonstrate that the peptide LyeTx I mnΔK is a potential prototype for the development of new effective and safe antibacterial agents against CRAB.

The increasing use of antibiotics in animal production has become an emergent environmental problem. The large percentages of applied antibiotic doses eliminated in animal excrement often end up contaminating water resources, which are then used for irrigation - compromising agricultural production and/or food security. Here, we evaluated the effects of crop irrigation with water artificially contaminated by enrofloxacin (10 μg l -1 ) and its accumulation in soybean, bean, and corn tissues. Grain production was evaluated on the basis of grain dry weight plant -1 , while enrofloxacin and ciprofloxacin (its breakdown metabolite) concentrations in plant tissues were evaluated by HPLC after harvesting. Diminished production was observed only in soybean plants irrigated with antibiotic-contaminated water. Enrofloxacin [1.68 ng g fresh weight (FW) -1 to 26.17 µg g FW -1 ] and ciprofloxacin (8.23 ng g FW -1 to 51.05 ng g FW -1 ), were found in all of the plant tissues (roots, leaves, and seeds) of the three species. Regardless of the species, the highest enrofloxacin concentrations were observed in their roots, followed by the leaves and seeds, while ciprofloxacin concentrations varied among the different plant tissues of the different species. The presence of enrofloxacin in the water used for irrigating soybeans can result in productivity losses and, as that antibiotic was encountered in plant tissues (leaves and seeds) of all of the three species analyzed that are consumed in the diets of both humans and animals, it can interfere with food security., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Mayaro fever is an infection caused by Mayaro virus (MAYV) that stands out among the neglected diseases transmitted by arthropods. Brazil is the country with the highest number of confirmed cases of MAYV infection. However, epidemiological surveillance studies conducted in Brazil are decentralized and focus on small outbreaks and unconfirmed cases. Thus, the aim of this review was to determine the general epidemiological profile of MAYV infections in Brazil. Several medical databases (i.e., PUBMED/MEDLINE, Scopus, Cochrane Library, LILACS, SciELO, and Biblioteca Virtual em Saúde) were searched for studies reporting cases of MAYV infections in Brazilian patients. Then, the rate of exposure to MAYV in Brazil was analyzed using RStudio® Software. We identified 37 studies published from 1957 to 2019, containing data of 12,374 patients from 1955 to 2018. The general rate of exposure to MAYV in Brazil was 10% (95% CI; 0.04-0.22), with 1,304 reported cases. The highest incidence of MAYV infection was found in the northern region (13%; 95% CI; 0.05-0.29), with 1,142 cases (88% of all cases). Furthermore, autochthonous MAYV cases have also been reported in the Central West (8%; 95% CI; 0.03-0.18) and Southeast (0.4%; 95% CI; 0.00-0.28). The states with the highest number of cases are Amazonas (490 cases), Pará (276 cases), and Goiás (87 cases). In conclusion, the general rate of exposure to MAYV in Brazil between 1955 and 2018 was considerable, especially in the Legal Amazon, in which 93% of cases were reported.

The emergence of novel coronavirus (SARS-CoV-2) in 2019 in China marked the third outbreak of a highly pathogenic coronavirus infecting humans. The novel coronavirus disease (COVID-19) spread worldwide, becoming an emergency of major international concern. However, even after a decade of coronavirus research, there are still no licensed vaccines or therapeutic agents to treat the coronavirus infection. In this context, apitherapy presents as a promising source of pharmacological and nutraceutical agents for the treatment and/or prophylaxis of COVID-19. For instance, several honeybee products, such as honey, pollen, propolis, royal jelly, beeswax, and bee venom, have shown potent antiviral activity against pathogens that cause severe respiratory syndromes, including those caused by human coronaviruses. In addition, the benefits of these natural products to the immune system are remarkable, and many of them are involved in the induction of antibody production, maturation of immune cells, and stimulation of the innate and adaptive immune responses. Thus, in the absence of specific antivirals against SARS-CoV-2, apitherapy could offer one hope toward mitigating some of the risks associated with COVID-19., (© 2020 John Wiley & Sons Ltd.)

Skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) require the development of new and effective topical antibiotics. In this context, melittin, the main component of apitoxin, has a potent antibacterial effect. However, little is known regarding the anti-inflammatory potential this peptide in infection models, or its ability to induce clinically important resistance. Here, we aimed to conduct an in-depth characterization of the antibacterial potential of melittin in vitro and evaluate the pharmaceutical potential of an ointment containing melittin for the treatment of non-surgical infections induced by MRSA. The minimum inhibitory concentration of melittin varied from 0.12 to 4 μM. The antibacterial effect was mainly bactericidal and fast (approximately 0.5 h after incubation) and was maintained even in stationary cells and mature MRSA biofilms. Melittin interacts synergistically with beta-lactams and aminoglycosides, and its ability to form pores in the membrane reverses the resistance of vancomycin-intermediate Staphylococcus aureus (VISA) to amoxicillin, and vancomycin. Its ability to induce resistance in vitro was absent, and melittin was stable in several conditions often associated with infected wounds. In vivo, aointment containing melittin reduced bacterial load and the content of pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin-6 (IL-6), and IL-1 beta. Collectively, these data point to melittin as a potential candidate for topical formulations aimed at the treatment of non-surgical infections caused by MRSA., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The novel human coronavirus (SARS-CoV-2), the causative agent of COVID-19, has quickly become a threat to the public health and economy worldwide. Despite the severity of some cases, there are no current pathogen-specific antivirals available to treat the disease. Therefore, many studies have focused on the evaluation of the anti-SARS-CoV-2 activity of clinically available drugs. Here, we conducted a systematic review to describe the drug repositioning strategy against SARS-CoV-2 and to discuss the clinical impact of this approach in the current pandemic context. The systematic review was performed on March 23, 2020, using PubMed/MEDLINE, Scopus, Cochrane Library, and Biblioteca Virtual de Saúde (BVS). The data were summarized in tables and critically analyzed. After the database search, 12 relevant studies were identified as eligible for the review. Among the drugs reported in these studies, 57 showed some evidence of antiviral activity. Antivirals, especially antiretrovirals, are the main class of therapeutic agents evaluated against COVID-19. Moreover, studies have reported the anti-SARS-CoV-2 activity of antitumor (16%; 9/57), antimalarial (7%, 4/57), and antibacterial (5%; 3/57) agents. Additionally, seven pharmacological agents (chloroquine, tetrandrine, umifenovir (arbidol), carrimycin, damageprevir, lopinavir/ritonavir) are in phase IV of clinical trials. Due to the evidence of the anti-SARS-CoV-2 activity of various clinically available agents, drug repositioning stands out as a promising strategy for a short-term response in the fight against the novel coronavirus.

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.

The physiological responses of the aquatic liverwort Ricciocarpus natans to ciprofloxacin (Cipro) exposure under different growth temperatures were investigated. Cipro appears to act as an inhibitor of mitochondrial Complex III by blocking the oxidation of quinol, resulting in the formation of hydrogen peroxide (H 2 O 2 ). H 2 O 2 accumulation upon Cipro exposure is responsible for decreased photosynthesis in plants. The amount of H 2 O 2 in plants is kept under control by antioxidant enzymes, whose activities are central to the responses of plants to Cipro yet are influenced by temperature. Increased temperature favored Cipro uptake by plants as well as its deleterious effects on mitochondrial activity; however, it also favored the activity of antioxidant enzymes, thereby preventing the exacerbation of the deleterious effects of Cipro. The uptake of Cipro by plants appears to be largely a passive process, although some uptake must be driven by an energy-consuming process. Ricciocarpus natans should be considered for programs aimed at the reclamation of Cipro since this plant exhibits high Cipro-tolerance, the capacity for accumulation and increased uptake rates of the antibiotic with increasing temperatures (from 20 to 30 °C)., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We investigated the ability of the aquatic fern Azolla to take up ciprofloxacin (Cipro), as well as the effects of that antibiotic on the N-fixing process in plants grown in medium deprived (-N) or provided (+N) with nitrogen (N). Azolla was seen to accumulate Cipro at concentrations greater than 160 μg g -1 dry weight when cultivated in 3.05 mg Cipro l -1 , indicating it as a candidate for Cipro recovery from water. Although Cipro was not seen to interfere with the heterocyst/vegetative cell ratios, the antibiotic promoted changes with carbon and nitrogen metabolism in plants. Decreased photosynthesis and nitrogenase activity, and altered plant's amino acid profile, with decreases in cell N concentrations, were observed. The removal of N from the growth medium accentuated the deleterious effects of Cipro, resulting in lower photosynthesis, N-fixation, and assimilation rates, and increased hydrogen peroxide accumulation. Our results shown that Cipro may constrain the use of Azolla as a biofertilizer species due to its interference with nitrogen fixation processes., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

We investigate the physiological responses and antibiotic-uptake capacity of Lemna minor exposed to ciprofloxacin. Ciprofloxacin (Cipro) induced toxic effects and hormesis in plants by significantly modifying photosynthesis and respiration pathways. A toxic effect was induced by a concentration ≥1.05mg ciprofloxacin l -1 while hormesis occurs at the lowest concentration studied (0.75mg ciprofloxacin l -1 ). By impairing normal electron flow in the respiratory electron transport chain, ciprofloxacin induces hydrogen peroxide (H 2 O 2 ) production. The ability of plants to cope with H 2 O 2 accumulation using antioxidant systems resulted in stimulation/deleterious effects to photosynthesis by Cipro. Cipro-induced oxidative stress was also associated with the ability of L. minor plants to uptake the antibiotic and, therefore, with plant-uptake capacity. Our results indicate that instead of being a photosystem II binding molecule, Cipro induces oxidative stress by targeting the mitochondrial ETC, which would explain the observed effects of the antibiotic on non-target eukaryotic organisms. The selection of plants species with a high capacity to tolerate oxidative stress may constitute a strategy to be used in Cipro-remediation programs., (Copyright © 2017 Elsevier B.V. All rights reserved.)