Staphylococcus aureus osteomyelitis leads to extensive bone destruction. Osteoclasts are bone resorbing cells that are often increased in bone infected with S. aureus. The cytokine RANKL is essential for osteoclast formation under physiological conditions but in vitro evidence suggests that inflammatory cytokines may by-pass the requirement for RANKL. The goal of this study was to determine whether RANKL-dependent osteoclast formation is essential for the bone loss that occurs in a murine model of S. aureus osteomyelitis. To this end, humanized-RANKL mice were infected by direct inoculation of S. aureus into a unicortical defect in the femur. Mice were treated with vehicle or denosumab, a human monoclonal antibody that inhibits RANKL, both before and during a 14-day infection period. The severe cortical bone destruction caused by infection was completely prevented by denosumab administration even though the bacterial burden in the femur was not affected. Osteoclasts were abundant near the inoculation site in vehicle-treated mice but absent in denosumab-treated mice. In situ hybridization demonstrated that S. aureus infection potently stimulated RANKL expression in bone marrow stromal cells. The extensive reactive bone formation that occurs in this osteomyelitis model was also reduced by denosumab administration. Lastly, there was a notable lack of osteoblasts near the infection site suggesting that the normal coupling of bone formation to bone resorption was disrupted by S. aureus infection. These results demonstrate that RANKL-mediated osteoclast formation is required for the bone loss that occurs in S. aureus infection and suggest that disruption of the coupling of bone formation to bone resorption may also contribute to bone loss in this condition.

Staphylococcus aureus is a Gram-positive bacteria with the greatest impact in the clinical area, due to the high rate of infections and deaths reaching every year. A previous scenario is associated with the bacteria\'s ability to develop resistance against conventional antibiotic therapies as well as biofilm formation. The above situation exhibits the necessity to reach new effective strategies against this pathogen. Flourensia retinophylla is a medicinal plant commonly used for bacterial infections treatments and has demonstrated antimicrobial effect, although its effect against S. aureus and bacterial biofilms has not been investigated. The purpose of this work was to analyze the antimicrobial and antibiofilm potential of F. retinophylla against S. aureus. The antimicrobial effect was determined using an ethanolic extract of F. retinophylla. The surface charge of the bacterial membrane, the K+ leakage and the effect on motility were determined. The ability to prevent and remove bacterial biofilms was analyzed in terms of bacterial biomass, metabolic activity and viability. The results showed that F. retinophylla presents inhibitory (MIC: 250 µg/mL) and bactericidal (MBC: 500 µg/mL) activity against S. aureus. The MIC extract increased the bacterial surface charge by 1.4 times and the K+ concentration in the extracellular medium by 60%. The MIC extract inhibited the motility process by 100%, 61% and 40% after 24, 48 and 72 h, respectively. The MIC extract prevented the formation of biofilms by more than 80% in terms of biomass production and metabolic activity. An extract at 10 × MIC reduced the metabolic activity by 82% and the viability by ≈50% in preformed biofilms. The results suggest that F. retinophylla affects S. areus membrane and the process of biofilm formation and removal. This effect could set a precedent to use this plant as alternative for antimicrobial and disinfectant therapies to control infections caused by this pathogen. In addition, this shrub could be considered for carrying out a purification process in order to identify the compounds responsible for the antimicrobial and antibiofilm effect.

The development of new drugs derived from plant sources is of significant interest in modern pharmacy. One of the promising plant sources for introduction into pharmaceuticals is Tripleurospermum inodorum (L.) Sch. Bip., also known as Tripleurospermum perforatum (Merat.) M. This plant has been shown to possess various biological activities, including anti-inflammatory, antimicrobial, and antimycotic activities, among others. However, a review of the current literature reveals a paucity of studies investigating the chemical composition of the herb Tripleurospermum inodorum (L.) Sch. Bip. This study presents the development of a method for obtaining an extract of the herb Tripleurospermum inodorum (L.) Sch. Bip. enriched with flavonoids, harvested before flowering and butonization. This study focused on determining the optimal conditions for extraction, including the concentration of the extractant (ethanol), extraction time, raw material/extractant ratio, extraction frequency, complexation reaction time, amount of aluminum chloride solution, and amount of diluted acetic acid. The results indicate that herbs harvested during this specific period exhibited a higher flavonoid content compared to those collected during butonization and flowering. Moreover, this study demonstrated that the flavonoid content could exceed 7% mg REq/100 g D.W. through a one-hour extraction process. Furthermore, the flavonoid content was found to be 7.65 ± 0.03 mg REq/100 g D.W. following a three-minute ultrasound-assisted extraction process, followed by thermal extraction. A qualitative analysis identified a variety of phenolic compounds in the extract, such as chlorogenic acid, 5-O-p-coumaroylquinic acid, 1-O-p-coumaroylquinic acid, luteolin-7-glucoside, quercetin-3-glucoside, luteolin-7-rutinoside, 3,5-O-dicaffeoylquinic acid, quercetin-3-O-malonylglucoside, apigenin-7-glucoside, luteolin-3-malonylglucoside, cynarin, rhamnetin-3-(O-dimethyl rhamnosyl glucosylglucoside), and luteolin. Moreover, this study demonstrated the antimicrobial, anti-inflammatory, anticoagulant, anti-aggregation, and antioxidant activities of the aqueous alcoholic extract from T. inodorum herb (ETIH) against pathogens such as Staphylococcus aureus, Escherichia coli, and Candida albicans. Additionally, the extract exhibited comparable anti-inflammatory effects on diclofenac sodium. These findings contribute to the understanding of the potential pharmacological applications of the developed herb extract.

The mec-independent oxacillin non-susceptible S. aureus (MIONSA) strains represent a great clinical challenge, as they are not easily detected and can lead to treatment failure. However, the responsible molecular mechanisms are still very little understood. Here, we studied four clinical ST8-MSSA-t024 isolates recovered during the course of antibiotic treatment from a patient suffering successive episodes of bacteremia. The first isolates (SAMS1, SAMS2, and SAMS3) were susceptible to cefoxitin and oxacillin. The last one (SA2) was susceptible to cefoxitin, resistant to oxacillin, lacked mec genes, and had reduced susceptibility to teicoplanin. SA2 showed higher β-lactamase activity than SAMS1. However, β-lactamase hyperproduction could not be linked to oxacillin resistance as it was not inhibited by clavulanic acid, and no genetic changes that could account for its hyperproduction were found. Importantly, we hereby report the in vivo acquisition and coexistence of different adaptive mutations in genes associated with peptidoglycan synthesis (pbp2, rodA, stp1, yjbH, and yvqF/vraT), which is possibly related with the development of oxacillin resistance and reduced susceptibility to teicoplanin in SA2. Using three-dimensional models and PBP binding assays, we demonstrated the high contribution of the SA2 PBP2 Ala450Asp mutation to the observed oxacillin resistance phenotype. Our results should be considered as a warning for physicians and microbiologists in the region, as MIONSA detection and treatment represent an important clinical challenge.

OBJECTIVE: Bovine mastitis, predominantly associated with gram-positive Staphylococcus aureus, poses a significant threat to dairy cows, leading to a decline in milk quality and volume with substantial economic implications.
OBJECTIVE: This study investigated the incidence, virulence, and antibiotic resistance of S. aureus associated with mastitis in dairy cows.
METHODS: Fifty milk-productive cows underwent a subclinical mastitis diagnosis, and the S. aureus strains were isolated. Genomic DNA extraction, sequencing, and bioinformatic analysis were performed, supplemented by including 124 S. aureus genomes from cows with subclinical mastitis to enhance the overall analysis.
RESULTS: The results revealed a 42% prevalence of subclinical mastitis among the cows tested. Genomic analysis identified 26 sequence types (STs) for all isolates, with Mexican STs belonging primarily to CC1 and CC97. The analyzed genomes exhibited multidrug resistance to phenicol, fluoroquinolone, tetracycline, and cephalosporine, which are commonly used as the first line of treatment. Furthermore, a similar genomic virulence repertoire was observed across the genomes, encompassing the genes related to invasion, survival, pathogenesis, and iron uptake. In particular, the toxic shock syndrome toxin (tss-1) was found predominantly in the genomes isolated in this study, posing potential health risks, particularly in children.
CONCLUSIONS: These findings underscore the broad capacity for antibiotic resistance and pathogenicity by S. aureus, compromising the integrity of milk and dairy products. The study emphasizes the need to evaluate the effectiveness of antibiotics in combating S. aureus infections.

UNASSIGNED: Staphylococcus aureus infections are a significant cause of morbidity and mortality in pediatric populations worldwide. The Staphylo Research Network conducted an extensive study on pediatric patients across Colombia from 2018 to 2021. The aim of this study was to describe the epidemiological and microbiological characteristics of S. aureus in this patient group.
UNASSIGNED: We analyzed S. aureus isolates from WHONET-reporting centers. An \"event\" was a positive culture isolation in a previously negative individual after 2 weeks. We studied center characteristics, age distribution, infection type, and antibiotic susceptibilities, comparing methicillin sensitive (MSSA) and resistant S. aureus (MRSA) isolates.
UNASSIGNED: Isolates from 20 centers across 7 Colombian cities were included. Most centers (80%) served both adults and children, with 55% offering oncology services and 85% having a PICU. We registered 8,157 S. aureus culture isolations from 5,384 events (3,345 MSSA and 1,961 MRSA) in 4,821 patients, with a median age of 5 years. Blood (26.2%) and skin/soft tissue (18.6%) were the most common infection sources. Most isolates per event remained susceptible to oxacillin (63.2%), clindamycin (94.3%), and TMP-SMX (98.3%). MRSA prevalence varied by city (<0.001), with slightly higher rates observed in exclusively pediatric hospitals. In contrast, the MRSA rate was somewhat lower in centers with Antimicrobial Stewardship Program (ASP). MRSA was predominantly isolated from osteoarticular infections and multiple foci, while MSSA was more frequently associated with recurrent infections compared to MRSA.
UNASSIGNED: This is the largest study of pediatric S. aureus infections in Colombia. We found MSSA predominance, but resistance have important regional variations. S. aureus remains susceptible to other commonly used antibiotics such as TMP-SMX and clindamycin. Ongoing monitoring of S. aureus infections is vital for understanding their behavior in children. Prospective studies within the Staphylored LATAM are underway for a more comprehensive clinical and genetic characterization.

Sterol derivatives are a crucial part of liposomes, as their concentration and nature can induce significant alternations in their characteristic features. For natural liposomal-based (phospholipid-based) studies, the bulk literature is already present depicting the role of the concentration or nature of different sterol derivatives in modulation of membrane properties. However, the studies aiming at evaluating the effect of sterol derivatives on synthetic liposomal assemblies are limited to cholesterol (Chl), and a comparative effect with other sterol derivatives, such as ergosterol (Erg), has never been studied. To fill this research gap, through this work, we intend to provide insights into the concentration-dependent effect of two sterol derivatives (Chl and Erg) on a synthetic liposomal assembly (i.e., metallosomes) prepared via thin film hydration route using a double-tailed metallosurfactant fabricated by modifying cetylpyridinium chloride with cobalt (Co) (i.e., Co:CPC II). The morphological evaluations with cryogenic-transmission electron microscopy (cryo-TEM), atomic force microscopy (AFM), and field emission-scanning electron microscopy (FE-SEM) indicated that metallosomes retained their spherical morphology irrespective of the nature and concentration of sterol derivatives. However, the size, ζ-potential, and lamellar width values were significantly modified with the incorporation of sterol derivatives in a concentration-dependent manner. In-depth studies affirmed that the extent of modulation of the bilayer in terms of hydrophobicity, fluidity, and rigidity was more severe with Chl than Erg. Such differences in the membrane properties lead to their contrasting behavior in the delivery of the broad-spectrum active compound \"curcumin\". From entrapment to in vitro behavior, the metallosomes demonstrated dissimilar behavior as even though Erg-modified metallosomes (at higher concentrations of Erg) exhibited low entrapment efficiency, they still could easily release >80% of the entrapped drug. In vitro studies conducted with Staphylococcus aureus bacterial cultures further revealed an interesting pattern of activity as the incorporation of Chl reduced the toxicity of the self-assembly, whereas their Erg-modified counterparts yielded slightly augmented toxicity toward these bacterial cells. Furthermore, Chl- and Erg-modified assemblies also exhibited contrasting behavior in their interaction studies with bacterial DNA.

Biofilms are complex communities of microorganisms that cause systemic infections, resistance development and delay in healing wounds. Biofilms can form in various parts of the human body, such as the teeth, lungs, urinary tract, and wounds. Biofilm complicates the effects of antibiotics in treating infections. In search of a cure, a plant-based phyto component was selected for this investigation as an anti-quorum-mediated biofilm restricting agent in Gram-negative Chromobacterium violaceum and Gram-positive Staphylococcus aureus. The bioactive components in Delonix elata (DE) ethyl acetate extract were identified using Gas chromatography and mass spectrometry. The extract was examined for toxicity using 3T3 cell lines and brine shrimp and ascertained to be non-toxic. Violacein was inhibited up to 68.81 % in C. violaceum at 0.6 mg/ml concentration. Hemolysin synthesis impediments in C. violaceum and S. aureus were 80 % and 51.35 %, respectively, at 0.6 mg/ml of DE extract. At 0.6 mg/ml, EPS was abated by up to 49 % in C. violaceum and 35.26 % in S. aureus. DE extract prevented biofilm formation in C. violaceum and S. aureus up to 76.45 % and 58.15 %, respectively, while associated eDNA was suppressed up to 67.50 % and 53.47 % at the respective sub-MIC concentrations. Expression of genes such as cviI, cviR, vioA, vioB, and vioE were dramatically reduced in C. violaceum, while genes such as agrA, sarA, fnbA, and fnbB were significantly reduced in S. aureus. Docking demonstrates that two or more DE molecules bind efficiently to the QS receptors of C. violaceum and S. aureus. Thus, DE extract can be investigated for therapeutic purposes against pathogenic microorganisms by rendering them less virulent through quorum quenching mediated action.

FeS clusters are prosthetic groups present in all organisms. Proteins with FeS centers are involved in most cellular processes. ISC and SUF are machineries necessary for the formation and insertion of FeS in proteins. Recently, a phylogenetic analysis on more than 10,000 genomes of prokaryotes have uncovered two new systems, MIS and SMS, which were proposed to be ancestral to ISC and SUF. SMS is composed of SmsBC, two homologs of SufBC(D), the scaffolding complex of SUF. In this review, we will specifically focus on the current knowledge of the SUF system and on the new perspectives given by the recent discovery of its ancestor, the SMS system.

UNASSIGNED: Staphylococcus aureus (S. aureus) is one of the pathogens strongly implicated in hospital infections. Data on the resistance and molecular characteristics of this bacterium are rare in Mali.
UNASSIGNED: This study aimed to evaluate the antibiotic resistance patterns, virulence factors of S. aureus isolates from pleural fluid infections in hospitalized patients.
UNASSIGNED: Pleural effusion samples were obtained by thoracentesis for bacteriological examination from October 2021 to December 2022 at the \"Hôpital du Mali\" teaching hospital. Comorbidities such as HIV/AIDS and diabetes were assessed. Standard microbiological procedures were used for bacterial identification. The disk diffusion method was used to identify methicillin-resistant S. aureus. The PCR amplification method was used to detect the following genes: lukE/D, sek, bsa, sel, and sep.
UNASSIGNED: This study analyzed 6096 samples from inpatients and found a pooled frequency of bacterial pleuritis of 526 (8.6%) in thoracic surgery and pediatric wards. S. aureus was isolated in 52 (9.88%) cases, of which 39 (75%) isolates were MRSA. There was no significant difference between the sexes (p = 1.00). The median age of the patients was 30 years. All S. aureus isolates showed resistance to penicillin-G. The leucocidin lukE/D toxin was detected in 7.7% of thoracic surgery patients, but sek, bsa, sel, and sep toxins were not found.
UNASSIGNED: In this study, we found a high frequency of S. aureus (and MRSA) in pleurisy patients at the \"Hôpital du Mali\". Only the leukocidin lukE/D was found. The empirical treatment protocol for pleurisy may need revision. Clindamycin, linezolid, teicoplanin, daptomycin, fosfomycin, vancomycin, moxifloxacin and fusidic acid were the most active antibiotics on our isolates in this study. Infection prevention measures, active surveillance, and effective therapeutic options are recommended.