New medicines for the treatment of bacterial biofilm formation are required. For this reason, this study shows the in vitro activity of betulinic acid (BA), ursolic acid (UA) and their twenty derivatives against planktonic and biofilm cells (gram-positive bacterial pathogens: Enterococcus faecalis, Staphylococcus aureus and Staphylococcus epidermidis). We evaluated the antibiofilm activity (through the crystal violet method), as well as the antibacterial activity via absorbance (OD₆₀₀) at concentrations of 5, 25 and 100 µM. Likewise, the cytotoxicity of all compounds was evaluated on a kidney African green monkey (VERO) cell line at the same concentration, by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) methodology. We verified for the first time whether different groups at carbon 3 (C-3) of triterpenes may interfere in the antibiofilm activity with minimal or no antibacterial effect. After the screening of 22 compounds at three distinct concentrations, we found antibiofilm activity for eight distinct derivatives without antibiotic effect. In particular, the derivative 2f, with an isopentanoyl ester at position C-3, was an antibiofilm activity against S. aureus without any effect upon mammalian cells.

New ecosystems are being actively mined for new bioactive compounds. Because of the large amount of unexplored biodiversity, bacteria from marine environments are especially promising. Further, host-associated microbes are of special interest because of their low toxicity and compatibility with host health. Here, we identified and characterized biosynthetic gene clusters encoding antimicrobial compounds in host-associated enterococci recovered from fecal samples of wild marine animals remote from human-affected ecosystems. Putative biosynthetic gene clusters in the genomes of 22 Enterococcus strains of marine origin were predicted using antiSMASH5 and Bagel4 bioinformatic software. At least one gene cluster encoding a putative bioactive compound precursor was identified in each genome. Collectively, 73 putative antimicrobial compounds were identified, including 61 bacteriocins (83.56%), 10 terpenes (13.70%), and 2 (2.74%) related to putative nonribosomal peptides (NRPs). Two of the species studied, Enterococcus avium and Enterococcus mundtti, are rare causes of human disease and were found to lack any known pathogenic determinants but yet possessed bacteriocin biosynthetic genes, suggesting possible additional utility as probiotics. Wild marine animal-associated enterococci from human-remote ecosystems provide a potentially rich source for new antimicrobial compounds of therapeutic and industrial value and potential probiotic application.

In methicillin-resistant Staphylococcus aureus (MRSA) treatment, the vancomycin minimum inhibitory concentration (MIC) increase, vancomycin heteroresistance (hVISA) presence, and accessory gene regulator (agr) dysfunction are predictors of vancomycin therapy failure. This study evaluated the association between vancomycin MIC (≥ 1.0 μg/mL) and agr dysfunction in invasive MRSA isolates. Vancomycin MIC, hVISA phenotype, agr group, and function were determined in 171 MRSA isolates obtained between 2014 and 2019 from hospitals in Porto Alegre, Brazil. All MRSA were susceptible to vancomycin; 16.4% of these had MIC ≥ 1.0 μg/mL. Seventeen MRSA isolates expressed the hVISA phenotype; 35.3% of them had MIC of 1.5 μg/mL. agr groups I (40.9%) and II (47.1%) were the most found groups for MRSA and hVISA isolates, respectively. The proportion of MRSA with vancomycin MIC ≥ 1.0 μg/mL in agr group II was significantly higher than in agr groups I and III (p = 0.002). agr dysfunction was observed in 4.7% (8/171) of MRSA, especially those with vancomycin MIC ≥ 1.0 μg/mL (p < 0.001). In addition, six isolates (35.3%; 6/17) with hVISA phenotype presented agr dysfunction, which was significantly higher than that in non-hVISA phenotype (p < 0.001). In conclusion, agr dysfunction in MRSA is associated with vancomycin MIC ≥ 1.0 μg/mL and hVISA phenotype, which suggests that agr dysfunction might confer potential advantages on MRSA to survive in invasive infections.

Streptococcus pneumoniae colonization patterns are influenced by host and environmental factors, which may be related to Invasive Pneumococcal Disease (IPD). Interestingly, COVID-19 pandemic witnessed a decline in the incidence of IPDs. Investigations with diligent data collection on the prevalence of nasopharyngeal colonization and associated serotypes during this unique period can yield novel insights. The aim of the current study was to assess the prevalence of S. pneumoniae carriage among children and adults who have sought care at emergency departments with suspected COVID-19. In this cross-sectional study, adults and children presenting with signs and symptoms likely associated with COVID-19 in two outpatient clinics in Southern Brazil were invited to participate. RT-PCR with a comprehensive molecular panel for pneumococcal identification of the 21 most prevalent serotypes in Latin America was performed on all enrolled subjects. Prevalence of pneumococcal carriage was assessed in the age groups (< 2, ≥ 2-5, ≥ 5-11, ≥ 11-18, ≥ 18-60, ≥ 60). A total of 1644 subjects were included in the study. Pneumococcal carriage was detected by PCR testing in 14.9% (245/1,644), and serotype identification occurred in 42.0% (103/245) of the participants, with a total frequency of 111. The most frequent serotype identified was 19A (25.2%, n = 28/111), followed by 6C/6D (17.1%, n = 19/111), and 23A (11.7%, n = 13/111), also highlighting the high frequency of non-vaccine serotypes found across all age groups. 19A serotype, as well other most frequent serotypes identified are not covered by the PCV-10 in a community setting where PCV-10 is widely available. This finding reinforces the need for continuous surveillance to determine the impact of pneumococcal vaccination and guide public health decision-making. High 19A serotype prevalence is critical in the decision-making process for electing the best options for pneumococcal conjugate vaccines.