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Tuberculosis (TB) remains an impactful infectious disease, leading to millions of deaths every year. Mycobacterium tuberculosis causes the formation of granulomas, which will determine, through the host-pathogen relationship, if the infection will remain latent or evolve into active disease. Early TB diagnosis is life-saving, especially among immunocompromised individuals, and leads to proper treatment, preventing transmission. This review addresses different approaches to diagnosing TB, from traditional methods such as sputum smear microscopy to more advanced molecular techniques. Integrating these techniques, such as polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP), has significantly improved the sensitivity and specificity of M. tuberculosis identification. Additionally, exploring novel biomarkers and applying artificial intelligence in radiological imaging contribute to more accurate and rapid diagnosis. Furthermore, we discuss the challenges of existing diagnostic methods, including limitations in resource-limited settings and the emergence of drug-resistant strains. While the primary focus of this review is on TB diagnosis, we also briefly explore the challenges and strategies for diagnosing non-tuberculous mycobacteria (NTM). In conclusion, this review provides an overview of the current landscape of TB diagnostics, emphasizing the need for ongoing research and innovation. As the field evolves, it is crucial to ensure that these advancements are accessible and applicable in diverse healthcare settings to effectively combat tuberculosis worldwide.

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The Human Respiratory Syncytial Virus (RSV) is the leading cause of acute respiratory infections in children. Currently, no safe, effective, or feasible option for pharmacological management of RSV exists. Hence, plant-derived natural compounds have been explored as promising antiviral agents. Mangifera indica is a globally distributed plant with reported anti-inflammatory, cardioprotective, and antiviral activities. Our study investigated the antiviral potential of a novel pectin from M. indica peels (PMi) and its chemically sulfated derivative (PSMi) against RSV in HEp-2 cells. The compounds were characterized using Fourier-transform infrared spectroscopy and nuclear magnetic resonance (NMR). NMR analysis revealed the presence of ester and carboxylic acid groups in PMi, and sulfation resulted in a sulfation degree of 0.5. PMi and PSMi showed no cytotoxic effects even at concentrations as high as 2000 µg/mL. PSMi completely inhibited RSV infectivity (100-1.56 µg/mL, 50 % inhibitory concentration of viral infectivity = 0.77 ± 0.11 µg/mL). The mechanism of action was investigated using the 50 % tissue culture infectious dose assay. PSMi displayed virucidal activity at concentrations from 100 to 6.25 µg/mL, and a significant reduction in viral infection was observed at all treatment times. Overall, PSMi is antiviral, cell-safe, and exhibits promising potential as an RSV treatment.

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Candida tropicalis is regarded as an opportunistic pathogen, causing diseases ranging from superficial infections to life-threatening disseminated infections. The ability of this yeast to form biofilms and develop resistance to antifungals represents a significant therapeutic challenge. Herein, the effect of geraniol (GER), alone and combined with fluconazole (FLZ), was evaluated in the planktonic and sessile cells of azole-resistant C. tropicalis. GER showed a time-dependent fungicidal effect on the planktonic cells, impairing the cell membrane integrity. Additionally, GER inhibited the rhodamine 6G efflux, and the molecular docking analyzes supported the binding affinity of GER to the C. tropicalis Cdr1 protein. GER exhibited a synergism with FLZ against the planktonic and sessile cells, inhibiting the adhesion of the yeast cells and the viability of the 48-h biofilms formed on abiotic surfaces. C. tropicalis biofilms treated with GER, alone or combined with FLZ, displayed morphological and ultrastructural alterations, including a decrease in the stacking layers and the presence of wilted cells. Moreover, neither GER alone nor combined with FLZ caused toxicity, and both treatments prolonged the survival of the Galleria mellonella larvae infected with azole-resistant C. tropicalis. These findings indicate that the combination of GER and FLZ may be a promising strategy to control azole-resistant C. tropicalis infections.

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The prompt and accurate identification of the etiological agents of viral respiratory infections is a critical measure in mitigating outbreaks. In this study, we developed and clinically evaluated a novel melting-curve-based multiplex real-time PCR (M-m-qPCR) assay targeting the RNA-dependent RNA polymerase (RdRp) and nucleocapsid phosphoprotein N of SARS-CoV-2, the Matrix protein 2 of the Influenza A virus, the RdRp domain of the L protein from the Human Respiratory Syncytial Virus, and the polyprotein from Rhinovirus B genes. The analytical performance of the M-m-qPCR underwent assessment using in silico analysis and a panel of reference and clinical strains, encompassing viral, bacterial, and fungal pathogens, exhibiting 100% specificity. Moreover, the assay showed a detection limit of 10 copies per reaction for all targeted pathogens using the positive controls. To validate its applicability, the assay was further tested in simulated nasal fluid spiked with the viruses mentioned above, followed by validation on nasopharyngeal swabs collected from 811 individuals. Among them, 13.4% (109/811) tested positive for SARS-CoV-2, and 1.1% (9/811) tested positive for Influenza A. Notably, these results showed 100% concordance with those obtained using a commercial kit. Therefore, the M-m-qPCR exhibits great potential for the routine screening of these respiratory viral pathogens.

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For decades, only two nitroheterocyclic drugs have been used as therapeutic agents for Chagas disease. However, these drugs present limited effectiveness during the chronic phase, possess unfavorable pharmacokinetic properties, and induce severe adverse effects, resulting in low treatment adherence. A previous study reported that N-(cyclohexylcarbamothioyl) benzamide (BTU-1), N-(tert-butylcarbamothioyl) benzamide (BTU-2), and (4-bromo-N-(3-nitrophenyl) carbamothioyl benzamide (BTU-3) present selective antiprotozoal activity against all developmental forms of Trypanosoma cruzi Y strain. In this study, we investigated the mechanism of action of these compounds through microscopy and biochemical analyses. Transmission electron microscopy analysis showed nuclear disorganization, changes in the plasma membrane with the appearance of blebs and extracellular arrangements, intense vacuolization, mitochondrial swelling, and formation of myelin-like structures. Biochemical results showed changes in the mitochondrial membrane potential, reactive oxygen species content, lipid peroxidation, and plasma membrane fluidity. In addition, the formation of autophagic vacuoles was observed. These findings indicate that BTU-1, BTU-2, and BTU-3 induced profound morphological, ultrastructural, and biochemical alterations in epimastigote forms, triggering an autophagic-dependent cell death pathway.

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Raoultella planticola harboring genes that confer resistance to antimicrobials, such as carbapenems, have been associated with severe infections in immunocompromised patients. In this study, we reported the first whole genome sequence of a Brazilian isolate of R. planticola and the genomic context of antibiotic resistance markers. By whole-genome sequencing (WGS) of a carbapenem-resistant R. planticola isolate, RpHUM1, we found 23 resistance-encoding genes belonging to 9 classes of antibiotics (aminoglycosides, ß-lactams, fluoroquinolones, fosfomycin, macrolides, phenicols, sulfonamides, tetracycline, and diaminopyrimidine derivatives) and 3 plasmids (RpHUM1pEaer-4382s, RpHUM1_pFDAARGOS_440, and RpHUM1pRSF1010). This isolate coharbored the genes blaKPC-2, which is carried by the plasmid RpHUM1pEaer-4382s, and blaNDM-1 and blaCTX-M-15 all located in the accessory genome. In addition, these genes were associated with, at least, one mobile genetic element. This comprehensive knowledge is of great importance for implementation of control measures to prevent the rapid dissemination of this neglected microorganism and their genetic resistance background.

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Wounds of an acute or chronic etiology affect millions of people worldwide, with increasing prevalence every year. Microbial infections are one of the main causes that impair the wound healing process, and Staphylococcus aureus, a commensal member of the skin microbiota, is one of the main causative agents of wound infections. Crucially, a high proportion of these infections are caused by methicillin-resistant Staphylococcus aureus, which, in addition to ß-lactams, has acquired resistance to almost all the antibacterial agents used to treat it, limiting therapeutic options. Studies on the antimicrobial and healing activities of extracts, essential oils, or metabolites obtained from native plants have been reported in many countries that have a diverse flora and traditions with the use of medicinal plants for the treatment of wound infections. Due to their great chemical diversity, plants have proven to be promising sources of bioactive molecules for the discovery and development of new drugs or strategies for the treatment of wounds. This review highlights the main herbal preparations that have antimicrobial and healing activities with potential for the treatment of wound infections caused by Staphylococcus aureus.

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Candida auris has been found to be a persistent colonizer of human skin and a successful pathogen capable of causing potentially fatal infection, especially in immunocompromised individuals. This fungal species is usually resistant to most antifungal agents and has the ability to form biofilms on different surfaces, representing a significant therapeutic challenge. Herein, the effect of metabolites of Pseudomonas aeruginosa LV strain, alone and combined with biologically synthesized silver nanoparticles (bioAgNP), was evaluated in planktonic and sessile (biofilm) cells of C. auris. First, the minimal inhibitory and fungicidal concentration values of 3.12 and 6.25 µg/mL, respectively, were determined for F4a, a semi-purified bacterial fraction. Fluopsin C and indolin-3-one seem to be the active components of F4a. Like the semi-purified fraction, they showed a time- and dose-dependent fungicidal activity. F4a and bioAgNP caused severe changes in the morphology and ultrastructure of fungal cells. F4a and indolin-3-one combined with bioAgNP exhibited synergistic fungicidal activity against planktonic cells. F4a, alone or combined with bioAgNP, also caused a significant decrease in the number of viable cells within the biofilms. No cytotoxicity to mammalian cells was detected for bacterial metabolites combined with bioAgNP at synergistic concentrations that presented antifungal activity. These results indicate the potential of F4a combined with bioAgNP as a new strategy for controlling C. auris infections.

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The present case study describes the dermatological manifestations of COVID-19 in a patient with genetic thrombophilia (MTHFR-C677T mutation) and the identification of a SARS-CoV-2 variant of interest (VOI). A female patient, 47 years old, unvaccinated, with thrombophilia, was diagnosed with COVID-19. She presented with urticarial and maculopapular eruptions from the seventh day of symptoms, which progressed to multiple lesions with dark centers (D-dimer value > 1450 ng/mL). The dermatological manifestations disappeared after 30 days, corroborating the reduction in D-dimer levels. Viral genome sequencing revealed infection by the VOI Zeta (P.2). Antibody testing, performed 30 days after the onset of symptoms, detected only IgG. The virus neutralization test showed the highest neutralizing titer for a P.2 strain, validating the genotypic identification. Lesions were suggested to be due to infection in skin cells causing a direct cytopathic effect or release of pro-inflammatory cytokines triggering erythematous and urticarial eruptions. In addition, vascular complications are also proposed to be due to the MTHFR mutation and increased D-dimer values. This case report is an alert about COVID-19 in patients with pre-existing vascular diseases, especially in unvaccinated patients, by VOI.

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Introduction: Cryptococcus neoformans is one of the leading causes of invasive fungal infections worldwide. Cryptococcal meningoencephalitis is the main challenge of antifungal therapy due to high morbidity and mortality rates, especially in low- and middle-income countries. This can be partly attributed to the lack of specific diagnosis difficulty accessing treatment, antifungal resistance and antifungal toxicity. Methods: In the present study, the effect of the synthetic thiourea derivative N-(butylcarbamothioyl) benzamide (BTU-01), alone and combined with amphotericin B (AmB), was evaluated in planktonic and sessile (biofilm) cells of C. neoformans. Results: BTU-01 alone exhibited a fungistatic activity with minimal inhibitory concentrations (MICs) ranging from 31.25 to 62.5 µg/mL for planktonic cells; and sessile MICs ranging from 125.0 to 1000.0 µg/mL. BTU-01 caused a concentration-dependent inhibitory activity on cryptococcal urease and did not interfere with plasma membrane fluidity. Molecular docking was performed on Canavalia ensiformis urease, and BTU-01 showed relevant interactions with the enzyme. The combination of BTU-01 and AmB exhibited synergistic fungicidal activity against planktonic and sessile cells of C. neoformans. Microscopic analysis of C. neoformans treated with BTU-01, alone or combined with AmB, revealed a reduction in cell and capsule sizes, changes in the morphology of planktonic cells; a significant decrease in the number of cells within the biofilm; and absence of exopolymeric matrix surrounding the sessile cells. Neither hemolytic activity nor cytotoxicity to mammalian cells was detected for BTU-01, alone or combined with AmB, at concentrations that exhibited antifungal activity. BTU-01 also displayed drug-likeness properties. Conclusion: These results indicate the potential of BTU-01, for the development of new strategies for controlling C. neoformans infections.

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BACKGROUND: Staphylococcus aureus is a major cause of a wide diversity of infections in humans, and the expression of Panton-Valentine Leukocidin (PVL) has been associated with severe clinical syndromes. OBJECTIVES: The present study aimed to investigate the prevalence of PVL-encoding genes in S. aureus isolated from clinical samples of inpatients with invasive infections in a teaching hospital in Southern Brazil. Furthermore, phenotypic and genotypic characteristics of bacterial isolates were analyzed. METHODS: A total of 98 S. aureus isolates recovered from different body sites were characterized according to their antimicrobial susceptibility profile, methicillin-resistance and SCCmec typing, genetic relatedness and occurrence of virulence-encoding genes, such as icaA, lukS-PV/lukF-PV, and tst. RESULTS: Sixty-eight (69.4%) isolates were classified as methicillin-resistant, and among them, four (5.9%) did not harbor the mecA gene. The mecA-harboring methicillin-resistant S. aureus (MRSA) isolates were grouped into SCCmec types I (6.3%), II (64.1%), III (6.3%), IV (15.6%), V (4.7%), and VI (1.6%). One isolate (1.6%) was classified as non-typeable (NT). Seventy isolates (71.4%) were classified as multidrug-resistant. The overall prevalence of virulence-encoding genes was as follows: icaA, 99.0%; tst, 27.5%; and lukS-PV/lukF-PV, 50.0%. The presence of tst gene was significantly higher (p < 0.001) in methicillin-susceptible S. aureus (MSSA) compared to MRSA isolates. CONCLUSION: The present study reports a high prevalence of multidrug-resistant S. aureus harboring lukS-PV/lukF-PV and tst genes in invasive infections. The continuous monitoring of the antimicrobial susceptibility profile and virulence of S. aureus is an important measure for the control of infections caused by this bacterium.

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The increase in multidrug-resistant microorganisms represents a global threat requiring the development novel strategies to fight bacterial infection. This study aimed to assess the effect of silver nanoparticles (bio-AgNPs) on bacterial growth, biofilm formation, production of virulence factors, and expression of genes related to the quorum-sensing (QS) system of P. aeruginosa PAO1 and PA14. Biofilm formation and virulence assays were performed with bio-AgNPs. RT-qPCR was carried out to determine the effect of bio-AgNPs on the QS regulatory genes lasI, lasR, rhlI, rhlR, pqsA, and mvfR. Bio-AgNPs had an MIC value of 62.50 µM, for both strains. Phenotypic and genotypic assays were carried out using sub-MIC values. Experimental results showed that treatment with sub-MICs of bio-AgNPs reduced (p < 0.05) the motility and rhamnolipids and elastase production in P. aeruginosa PAO1. In PA14, bio-AgNPs stimulated swarming and twitching motilities as well as biofilm formation and elastase and pyocyanin production. Bio-AgNP treatment increased (p < 0.05) the expression of QS genes in PAO1 and PA14. Despite the different phenotypic behaviors in both strains, both showed an increase in the expression of QS genes. Demonstrating that the bio-AgNPs acted in the induction of regulation. The possible mechanism underlying the action of bio-AgNPs involves the induction of the rhl and/or pqs system of PAO1 and of the las and/or pqs system of PA14. These results suggest that exposure to low concentrations of bio-AgNPs may promote the expression of QS regulatory genes in P. aeruginosa, consequently inducing the production of virulence factors such as elastase, pyocyanin, and biofilms.

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Leishmaniasis is a group of neglected diseases caused by parasites of the Leishmania genus. The treatment of Leishmaniasis represents a great challenge, because the available drugs present high toxicity and none of them is fully effective. Caryocar is a botanical genus rich in phenolic compounds, which leaves extracts have already been described by its antileishmanial action. Thus, we investigated the effect of pulp and peel extracts of the Caryocar coriaceum fruit on promastigote and amastigote forms of Leishmania amazonensis. Both extracts had antipromastigote effect after 24, 48, and 72 h, and this effect was by apoptosis-like process induction, with reactive oxygen species (ROS) production, damage to the mitochondria and plasma membrane, and phosphatidylserine exposure. Knowing that the fruit extracts did not alter the viability of macrophages, we observed that the treatment reduced the infection of these cells. Thereafter, in the in vitro infection context, the extracts showed antioxidant proprieties, by reducing NO, ROS, and MDA levels. Besides, both peel and pulp extracts up-regulated Nrf2/HO-1/Ferritin expression and increase the total iron-bound in infected macrophages, which culminates in a depletion of available iron for L. amazonensis replication. In silico, the molecular modeling experiments showed that the three flavonoids presented in the C. coriaceum extracts can act as synergistic inhibitors of Leishmania proteins, and compete for the active site. Also, there is a preference for rutin at the active site due to its greater interaction binding strength.Communicated by Ramaswamy H. Sarma.

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Cryptococcus neoformans is the leading cause of cryptococcosis, an invasive and potentially fatal infectious disease. Therapeutic failures are due to the increase in antifungal resistance, the adverse effects of drugs, and the unavailability of therapeutic regimens in low-income countries, which limit the treatment of cryptococcosis, increasing the morbidity and mortality associated with these infections. Thus, new antifungal drugs and innovative strategies for the cryptococcosis treatment are urgently needed. The aim of the present study was to evaluate the effect of ethyl acetate fraction (EAF) of Poincianella pluviosa stem bark on planktonic and biofilm mode of growth of C. neoformans. Furthermore, the interaction between the EAF and amphotericin B (AmB) was evaluated in vitro and in Galleria mellonella infection model. Minimal inhibitory concentrations (MICs) of EAF ranged from 125.0 to >1,000.0 µg/ml and >1,000.0 µg/ml for planktonic and sessile cells, respectively. The combination between EAF and AmB exhibited a synergistic fungicidal activity toward C. neoformans, with a fractional inhibitory concentration index (FICI) ranging from 0.03 to 0.06 and 0.08 to 0.28 for planktonic and sessile cells, respectively. Microscopy analyses of planktonic C. neoformans cells treated with EAF, alone or combined with AmB, revealed morphological and ultrastructural alterations, including loss of integrity of the cell wall and cell membrane detachment, suggesting leakage of intracellular content, reduction of capsule size, and presence of vacuoles. Moreover, EAF alone or combined with AmB prolonged the survival rate of C. neoformans-infected G. mellonella larvae. These findings indicate that P. pluviosa may be an important source of new compounds that can be used as a fungus-specific adjuvant for the treatment of cryptococcosis.

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BACKGROUND: Staphylococcus haemolyticus is one of the most frequently coagulasenegative staphylococci isolated from healthcare-associated infections, mainly those related to implanted medical devices. OBJECTIVES: This study aimed to determine the antimicrobial susceptibility profile and biofilm forming capacity of S. haemolyticus isolated from bloodstream infections. METHODS: A total of 40 S. haemolyticus isolates were characterized according to their genetic relatedness by repetitive element sequence based-PCR (REP-PCR), antimicrobial susceptibility profile, SCCmec typing, ability to form biofilm on abiotic surface and occurrence of putative genes related to biofilm formation. RESULTS: One S. haemolyticus was susceptible to all antimicrobials. The other isolates (n=39) were resistant to cefoxitin; and among them 34 (87.2%) harbored the mecA gene into the SCCmec type I (5.9%), type III (29.4%), type IV (5.9%) and type V (20.6%); and 38.2% isolates were designated as NT. Apart from cefoxitin, 94.9% of the isolates were resistant to at least four antimicrobial classes, and 32.5% displayed minimal inhibitory concentration (MIC) values higher than 4.0 µg/mL for vancomycin. All isolates formed biofilm on polystyrene surface and were classified as strong biofilm-producers, except for one isolate. All isolates were negative for icaA gene, and the prevalence of the other genes was as follows: atl, 100%; fbp, 92.5%; aap, 90.0%; and bap, 20.0%. CONCLUSION: This study reports a high prevalence of methicillin-resistant S. haemolyticus displaying decreased susceptibility to vancomycin with the ability to form strong biofilms on abiotic surface. The results support the importance of controlling the adequate use of antimicrobials for the treatment of staphylococcal infections.

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Pseudomonas aeruginosa is known for a high adaptive capacity due to the ability to synthesize several compounds that give advantages for competing with other microorganisms in the environment. The LV strain synthesizes bioactive compounds, mainly by secondary metabolism, with antitumor and antimicrobial activities against microbial pathogens.

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Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), is the largest pandemic in modern history with very high infection rates and considerable mortality. The disease, which emerged in China's Wuhan province, had its first reported case on December 29, 2019, and spread rapidly worldwide. On March 11, 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a pandemic and global health emergency. Since the outbreak, efforts to develop COVID-19 vaccines, engineer new drugs, and evaluate existing ones for drug repurposing have been intensively undertaken to find ways to control this pandemic. COVID-19 therapeutic strategies aim to impair molecular pathways involved in the virus entrance and replication or interfere in the patients' overreaction and immunopathology. Moreover, nanotechnology could be an approach to boost the activity of new drugs. Several COVID-19 vaccine candidates have received emergency-use or full authorization in one or more countries, and others are being developed and tested. This review assesses the different strategies currently proposed to control COVID-19 and the issues or limitations imposed on some approaches by the human and viral genetic variability.

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BACKGROUND: Staphylococcus aureus can asymptomatically colonize the human anterior nares and skin, and nasal colonization by this bacterium represents a potential risk for development of invasive infections. The aim of this study was to determine the prevalence of S. aureus nasal carriage among healthcare workers and students attending a university hospital and to characterize the isolates phenotypically and molecularly. METHODS: A cross-sectional study was performed with 324 volunteers. Cultures from nasal samples were obtained and S. aureus isolates were characterized according to their antimicrobial susceptibility profile and four virulence factors-encoding genes. MRSA isolates were characterized regarding their oxacillin/cefoxitin susceptibility, SCCmec, and REP-PCR types. Potential risks for S. aureus and MRSA carriage were analyzed. RESULTS: Of 324 nasal samples, 42.9% were identified as S. aureus, of which 28.8% were MRSA. S. aureus carriers were significantly higher in males and students (OR = 2.898, 95%CI 1.553-5.410); however, no variables were associated with MRSA carriage. All isolates were susceptible to vancomycin and the highest rate of resistance was observed for penicillin (90.6%). All isolates harbored the coa gene, and 97.8%, the icaA gene; 15.8% and 6.5% were positive for tst and lukS-PV/lukF-PV genes, respectively. Among MRSA isolates, 45% carried the mecA gene but were phenotypically susceptible to oxacillin/cefoxitin; two harbored the tst and none had lukS-PV/lukF-PV genes. All MRSAs were distributed into six SCCmec types and type I (62.5%) was the most frequent. REP-PCR typing identified four main clusters among MRSA isolates. CONCLUSION: High prevalence of healthcare workers and students were identified as nasal carriers of S. aureus exhibiting different antimicrobial resistance profiles, including mecA-positive oxacillin-susceptible S. aureus (OS-MRSA) and the presence of virulence-encoding genes. Both cohorts may represent potential sources for the emergence of a successful S. aureus strain highly adapted to the hospital environment.

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Chagas disease, caused by the protozoan Trypanosoma cruzi, is one of the main causes of death due to cardiomyopathy and heart failure in Latin American countries. The treatment of Chagas disease is directed at eliminating the parasite, decreasing the probability of cardiomyopathy and disrupting the disease transmission cycle. Benznidazole (BZ) and nifurtimox (Nfx) are recognized as effective drugs for the treatment of Chagas disease by the World Health Organization, but both have high toxicity and limited efficacy, especially in the chronic disease phase. At low doses, aspirin (ASA) has been reported to protect against T. cruzi infection. We evaluated the effectiveness of BZ in combination with ASA at low doses during the acute disease phase and evaluated cardiovascular aspects and cardiac lesions in the chronic phase. ASA treatment prevented the cardiovascular dysfunction (hypertension and tachycardia) and typical cardiac lesions. Moreover, BZ+ASA-treated mice had a smaller cardiac fibrotic area than BZ-treated mice. These results were associated with an increase in numbers of eosinophils and reticulocytes and levels of nitric oxide in the plasma and cardiac tissue of ASA-treated mice relative to respective controls. These effects of ASA and BZ+ASA in chronically infected mice were inhibited by pretreatment with the lipoxin A4 (LXA4) receptor antagonist Boc-2, indicating that the protective effects of ASA are mediated by ASA-triggered lipoxin. These results emphasize the importance of exploring new drug combinations for treatments of the acute phase of Chagas disease that are beneficial for patients with chronic disease.

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Streptococcus agalactiae or Group B Streptococcus (GBS) remains a leading cause of neonatal infections worldwide; and the maternal vaginal-rectal colonization increases the risk of vertical transmission of GBS to neonates and development of infections. This study reports the in vitro antibacterial effect of the oleoresin from Copaifera officinalis Jacq. L. in natura (copaiba oil) and loaded into carbomer-hydrogel against planktonic and sessile cells of GBS. First, the naturally extracted copaiba oil was tested for the ability to inhibit the growth and metabolic activity of planktonic and sessile GBS cells. The time-kill kinetics showed that copaiba oil exhibited a dose-dependent bactericidal activity against planktonic GBS strains, including those resistant to erythromycin and/or clindamycin [minimal bactericidal concentration (MBC) ranged from 0.06 mg/mL to 0.12 mg/mL]. Copaiba oil did not inhibit the growth of different Lactobacillus species, the indigenous members of the human microbiota. The mass spectral analyses of copaiba oil showed the presence of diterpenes, and the kaurenoic acid appears to be one of the active components of oleoresin from C. officinalis related to antibacterial activity against GBS. Microscopy analyses of planktonic GBS cells treated with copaiba oil revealed morphological and ultrastructural alterations, displaying disruption of the cell wall, damaged cell membrane, decreased electron density of the cytoplasm, presence of intracellular condensed material, and asymmetric septa. Copaiba oil also exhibited antibacterial activity against established biofilms of GBS strains, inhibiting the viability of sessile cells. Low-cost and eco-friendly carbomer-based hydrogels containing copaiba oil (0.5% - CARB-CO 0.5; 1.0% - CARB-CO 1.0) were then developed. However, only CARB-CO 1.0 preserved the antibacterial activity of copaiba oil against GBS strains. This formulation was homogeneous, soft, exhibited a viscoelastic behavior, and showed good biocompatibility with murine vaginal mucosa. Moreover, CARB-CO 1.0 showed a slow and sustained release of the copaiba oil, killing the planktonic and sessile (established biofilm) cells and inhibiting the biofilm formation of GBS on pre-coated abiotic surface. These results indicate that carbomer-based hydrogels may be useful as topical systems for delivery of copaiba oil directly into de vaginal mucosa and controlling S. agalactiae colonization and infection.