Detection of Staphylococcal Enterotoxins A and E and Methicillin Resistance in Staphylococcus aureus Strains From Moroccan Broiler Chicken Meat.

Foodborne epidemics have become a serious public health emergency worldwide. Foods of animal origin, in particular chicken meat, are considered to be potential vectors of pathogenic bacteria, particularly Staphylococcus aureus. This bacterium can be resistant in the form of methicillin-resistant S. aureus (MRSA) or produce enterotoxins leading to food poisoning when ingested. This study is aimed at exploring the virulence genes in S. aureus responsible for producing enterotoxins (staphylococcal enterotoxin [SE] A [sea] and SE E [see]) and determining the prevalence of MRSA in raw broiler meat in the Casa-Rabat region in Morocco. A quantitative (q) PCR (qPCR) assay, using specific primers for S. aureus (nuc) confirmation and detection of enterotoxin genes (sea and see), as well as the methicillin-resistant gene (mecA), was employed. Our findings indicated that all tested strains were positively identified as S. aureus. Among them, one isolate (1/54) tested positive for the see gene (1.85%), while none carried the sea gene. Furthermore, the mecA gene, indicative of MRSA, was present in 12/54 of the isolates (22.22%). The potential presence of MRSA in Moroccan poultry meat underscores a public health risk. Thus, stringent measures are imperative to curtail the contamination and proliferation of this bacterium during the slaughtering process, underscoring the importance of continuing research into the prevalence of MRSA colonization among poultry slaughterhouse personnel.

Investigating genomic diversity of Staphylococcus aureus associated with pediatric atopic dermatitis in South Africa.

Importance: Staphylococcus aureus frequently colonizes the skin and nose of patients with atopic dermatitis (AD), a disease associated with skin barrier dysfunction and chronic cutaneous inflammation. Published genomic studies on AD-associated S. aureus in pediatric populations in sub-Saharan Africa are limited. Objectives: To investigate the phenotypic and genomic diversity of S. aureus in children with and without AD during early childhood. Data setting and participants: A cross-sectional study of 220 children (aged 9-38 months) with AD (cases) and without AD (controls) from Cape Town and Umtata, South Africa. Main outcomes and measures: S. aureus phenotypic and genomic diversity were investigated using whole-genome sequencing, antibiotic susceptibility testing and biofilm microtiter assay. Results: Of the 124 S. aureus isolates recovered from 220 children, 96 isolates (79 cases and 17 controls) with high-quality sequences were analyzed. Isolates from cases showed greater phenotypic resistance to gentamicin (10%), rifampicin (4%), chloramphenicol (4%), and exhibited multidrug resistance (9%) than in controls. Furthermore, the isolates from cases formed stronger biofilms than those from controls (76% vs. 35%, p = 0.001), but showed no dominance of any virulence factor gene or mobile genetic elements. There was no significant difference in the distribution of immune evasion cluster types between cases and controls. However, IEC type G was identified only among cases. Conclusion and relevance: AD-associated S. aureus has phenotypic and genetic features that are important for successful pathogenic colonization and survival. Further studies are needed to assess the pathological implications of colonization of various S. aureus lineages in vivo to elucidate their pathological contribution to AD pathogenesis and pathophysiology.

QSAR Studies on a Class of Benzofuranene Cyanide Derivatives as Potential Inhibitors Targeting Staphylococcus aureus Sortase A.

BACKGROUND: Staphylococcus aureus is a widely distributed and highly pathogenic zoonotic bacterium. Sortase A represents a crucial target for the research and development of novel antibacterial drugs. OBJECTIVE: This study aims to establish quantitative structure-activity relationship models based on the chemical structures of a class of benzofuranene cyanide derivatives. The models will be used to screen new antibacterial agents and predict the properties of these molecules. METHOD: The compounds were randomly divided into a training set and a test set. A large number of descriptors were calculated using the software, and then the appropriate descriptors were selected to build the models through the heuristic method and the gene expression programming algorithm. RESULTS: In the heuristic method, the determination coefficient, determination coefficient of cross-validation, F-test, and mean squared error values were 0.530, 0.395, 9.006, and 0.047, respectively. In the gene expression programming algorithm, the determination coefficient and the mean squared error values in the training set were 0.937 and 0.008, respectively, while in the test set, they were 0.849 and 0.035. The results showed that the minimum bond order of a C atom and the relative number of benzene rings had a significant positive contribution to the activity of compounds. CONCLUSION: In this study, two quantitative structure-activity relationship models were successfully established to predict the inhibitory activity of a series of compounds targeting Staphylococcus aureus Sortase A, providing insights for further development of novel anti-Staphylococcus aureus drugs.

Antibacterial Activity and Mechanism of Lauric Acid Against Staphylococcus aureus and Its Application in Infectious Cooked Chicken.

Staphylococcus aureus contamination and prevention has always been a major concern for food industry. This work investigated the antibacterial activity and mechanisms of lauric acid (LA) against S. aureus. Results revealed 156 µg/mL was the minimum inhibitory concentration (MIC) for LA and it retarded growth rate of S. aureus. The inhibitory effect was enhanced with LA concentration. After being treated with 2 MIC LA for 24 h, the number of S. aureus decreased by 3.56 log colony-forming unit (CFU)/mL. Scanning electron microscopy profiling revealed that LA resulted in altered morphology of S. aureus cells. In addition, propidium iodide staining of flow cytometry suggested that LA treatment disrupted the cell membrane integrity. Changes in 8-anilino-1-naphthalenesulfonic acid fluorescence indicated a depolarization change in cell membrane fluidity. For practical applications, LA also displayed an antimicrobial potential in cooked chicken food model system, with 1.25-5 g/L of LA prolonging shelf life by 2 days at 4°C. Moreover, it had no adverse effect on pH values, color in cooked chicken meat, and even reduced lipid oxidation. To sum up, LA has great antimicrobial properties and is a candidate preservative for cooked meat food.

Clinical presentations and diagnostic approaches of pediatric necrotizing tracheobronchitis with influenza A virus and Staphylococcus aureus co-infections.

In March 2023, our pediatric intensive care unit (PICU) retrospectively examined six cases of pediatric necrotizing tracheobronchitis (NTB), focusing on co-infections with influenza A virus (IAV) and Staphylococcus aureus (S. aureus). This study aimed to elucidate NTB's clinical characteristics, diagnostics, and therapeutic approaches. Diagnostics included symptom assessment, microbiological testing that confirmed all patients were positive for IAV H1N1 with a predominant S. aureus co-infection, and bronchoscopy. The patients predominantly exhibited fever, cough, and dyspnea. Laboratory analysis revealed decreased lymphocyte counts and elevated infection markers like C-reactive protein and procalcitonin. Chest computed tomography (CT) scans detected tracheobronchial obstructions in half of the cases, while bronchoscopy showed severe mucosal congestion, edema, necrosis, and purulent-hemorrhagic exudates. Treatments encompassed comprehensive strategies like oxygen therapy, intubation, bronchoscopic interventions, thoracentesis, oseltamivir, and a regimen of antibiotics. Our findings suggested potential correlations between clinical markers, notably lymphocyte count and procalcitonin, and clinical interventions such as the number of rescues and intensive care unit (ICU) duration. This research highlights the importance of early detection and the role of bronchoscopy and specific markers in assessing NTB, advocating for continued research in larger cohorts to better understand its clinical trajectory and refine treatment approaches for this challenging pediatric disease.

Characterising the role of enolase in a stable Small Colony Variant of Staphylococcus aureus isolated from a diabetic foot infection patient with osteomyelitis.

The switch to alternate cell types by Staphylococcus aureus creates sub-populations even within an active population, that are highly resilient, tolerant to antibiotics and lack clinical symptoms of infection. These cells present a challenge for clinical treatment where even after initial intervention has seemingly cleared the infection, these alternate cell types persist within tissue to revert and cause disease. Small colony variants (SCV) are a cell type which facilitate persistent infection but clinically isolated SCVs are often unstable in laboratory conditions. We have isolated a pair of S. aureus isolates from an individual patient with osteomyelitis presenting with heterogenous phenotypes; a stable SCV (sSCV) and a SCV that reverts upon laboratory culturing to the usual, active and non-SCV cell type. Thus we are able use this pair to investigate and compare the genetic mechanisms that underlie the clinical variatons of SCV phenotype. The switch to the sSCV phenotype was associated with frameshift mutations in the enolase eno and the histidine kinase arlS. The phenoptye of the sSCV was an impeded growth dependent on amino acid catabolism and modulated biofilm. These mutations present potentially a new molecular mechanism which confer persistence within osteomyelitis.

The prebiotic effects of fructooligosaccharides enhance the growth characteristics of Staphylococcus epidermidis and enhance the inhibition of Staphylococcus aureus biofilm formation.

OBJECTIVE: Oligosaccharides have been shown to enhance the production of short chain fatty acids (SCFAs) by gut probiotics and regulate gut microbiota, to improve intestinal health. Recent research indicates that oligosaccharides may also positively impact skin microbiota by selectively promoting the growth of skin commensal bacteria and inhibiting pathogenic bacteria. However, the specific metabolic and regulatory mechanisms of skin commensal bacteria in response to oligosaccharides remain unclear. This study aims to explore the influence of four oligosaccharides on the growth and metabolism of Staphylococcus epidermidis and further identify skin prebiotics that can enhance its probiotic effects on the skin. METHODS: Fructooligosaccharides (FOS), isomaltooligosaccharide (IMO), galactooligosaccharides (GOS) and inulin were compared in terms of their impact on cell proliferation, SCFAs production of S. epidermidis CCSM0287 and the biofilm inhibition effect of their fermentation supernatants on Staphylococcus aureus CCSM0424. Furthermore, the effect of FOS on S. epidermidis CCSM0287 was analysed by the transcriptome analysis. RESULTS: All four oligosaccharides effectively promoted the growth of S. epidermidis CCSM0287 cells, increased the production of SCFAs, with FOS demonstrating the most significant effect. Analysis of the SCFAs indicated that S. epidermidis CCSM0287 predominantly employs oligosaccharides to produce acetic acid and isovaleric acid, differing from the SCFAs produced by gut microbiota. Among the four oligosaccharides, the addition of 2% FOS fermentation supernatant significantly inhibited S. aureus CCSM0424 biofilm formation. Furthermore, RNA sequencing revealed 162 differentially expressed genes (84 upregulated and 78 downregulated) of S. epidermidis CCSM0287 upon FOS treatment compared with glucose treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis highlighted differences in the amino acid synthesis pathway, particularly in terms of arginine biosynthesis. CONCLUSION: FOS promotes cell proliferation, increases the SCFA production of S. epidermidis CCSM0287 and enhance the inhibition of S. aureus biofilm formation, suggesting that FOS serves as a potential prebiotic for strain S. epidermidis CCSM0287.

OBJECTIF: Il a été démontré que les oligosaccharides améliorent la production d'acides gras à chaîne courte (AGCC) par les probiotiques intestinaux et régulent le microbiote intestinal, pour améliorer la santé intestinale. Des recherches récentes indiquent que les oligosaccharides peuvent également avoir un impact positif sur le microbiote cutané en favorisant sélectivement la croissance des bactéries commensales de la peau et en inhibant les bactéries pathogènes. Cependant, les mécanismes métaboliques et régulateurs spécifiques des bactéries commensales de la peau en réponse aux oligosaccharides restent incertains. Cette étude vise à étudier l'influence de quatre oligosaccharides sur la croissance et le métabolisme de Staphylococcus epidermidis, et à identifier de manière plus approfondie les prébiotiques cutanés qui peuvent améliorer ses effets probiotiques sur la peau. MÉTHODES: Les fructooligosaccharides (FOS), les isomaltooligosaccharides (IMO), les galactooligosaccharides (GOS) et l'inuline ont été comparés en termes d'impact sur la prolifération cellulaire, de production d'AGCC du S. epidermidis CCSM0287 et d'effet d'inhibition du biofilm de leurs surnageants de fermentation sur le staphylococoque CCSM0424. En outre, l'effet des FOS sur S. epidermidis CCSM0287 a été analysé par analyse du transcriptome. RÉSULTATS: Les quatre oligosaccharides ont efficacement favorisé la croissance des cellules du S. epidermidis CCSM0287, augmenté la production d'AGCC, le FOS démontrant l'effet le plus significatif. L'analyse des AGCC a indiqué que S. epidermidis CCSM0287 emploie principalement des oligosaccharides pour produire de l'acide acétique et de l'acide isovalérique, ce qui diffère des AAGC produites par le microbiote intestinal. Parmi les quatre oligosaccharides, l'ajout d'un surnageant de fermentation de FOS à 2% a inhibé significativement la formation du biofilm de S. aureus CCSM0424. En outre, le séquençage de l'ARN a révélé 162 gènes exprimés de manière différentielle (84 régulés à la hausse et 78 régulés à la baisse) de S. epidermidis CCSM0287 lors du traitement par FOS par rapport au traitement par glucose. L'analyse d'enrichissement de Kyoto Encyclopedia of Genes and Genomes (KEGG) a mis en évidence des différences dans la voie de synthèse des acides aminés, en particulier en termes de biosynthèse de l'arginine. CONCLUSION: Le FOS favorise la prolifération cellulaire, augmente la production des AGCC du S. epidermidis CCSM0287 et améliore l'inhibition de la formation du biofilm de S. aureus, ce qui indique que le FOS sert de prébiotique potentiel pour la souche S. epidermidis CCSM0287.

Antimicrobial and Cytotoxic Effect of Bornetella Nitida Green Algae Isolate on MCF-7 Breast Cancer.

Introduction: Marine algae are increasingly becoming a potential resource for new drugs. In recent decades, including Bornetella nitida (B. nitida). Meanwhile, antimicrobial and anticancer agents are the first line of choice for developing alternative compounds, considering the annually increasing resistant events. Therefore, this study aimed to examine the antimicrobial and cytotoxic potential of B. nitida isolate compounds. Methods: The B. nitida resulted in 2 compounds, sitosterol 3ß tetracosanoate and (E)-17-(8-ethyl-4,5,9-trimethyldec-6-en-2-yl)-13-methyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol. Both compounds were tested to have antibacterial effects against Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, Methicillin-resistant Staphylococcus Aureus (MRSA). Proliferation assay was conducted using the PrestoBlue™ Cell Viability Reagent, which was also used to measure the IC50 against MCF-7 breast cancer cells. Results: The results showed that (E)-17-(8-ethyl-4,5,9-trimethyldec-6-en-2-yl)-13-methyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol had antimicrobial activity against Staphylococcus aureus and IC50 value of 142.18 µg/mL against MCF-7 cells, while sitosterol 3ß tetracosanoate does not have any antimicrobial activity and IC50 value of 681.65 µg/mL. Moreover, the mechanism prediction using docking with caspase-3 receptor to induce apoptosis was also evaluated. Conclusion: Based on the results, (E)-17-(8-ethyl-4,5,9-trimethyldec-6-en-2-yl)-13-methyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol of B. nitida has great potential as an antimicrobial and anticancer agent.

The dynamics of Staphylococcal infection and their treatment with antibiotics and bacteriophage in the Galleria mellonella model system.

Critical to our understanding of infections and their treatment is the role the innate immune system plays in controlling bacterial pathogens. Nevertheless, many in vivo systems are made or modified such that they do not have an innate immune response. Use of these systems denies the opportunity to examine the synergy between the immune system and antimicrobial agents. In this study we demonstrate that the larva of Galleria mellonella is an effective in vivo model for the study of the population and evolutionary biology of bacterial infections and their treatment. To do this we test three hypotheses concerning the role of the innate immune system during infection. We show: i) sufficiently high densities of bacteria are capable of saturating the innate immune system, ii) bacteriostatic drugs and bacteriophages are as effective as bactericidal antibiotics in preventing mortality and controlling bacterial densities, and iii) minority populations of bacteria resistant to a treating antibiotic will not ascend. Using a highly virulent strain of Staphylococcus aureus and a mathematical computer-simulation model, we further explore how the dynamics of the infection within the short term determine the ultimate infection outcome. We find that excess immune activation in response to high densities of bacteria leads to a strong but short-lived immune response which ultimately results in a high degree of mortality. Overall, our findings illustrate the utility of the G. mellonella model system in conjunction with established in vivo models in studying infectious disease progression and treatment.

The Utilization Of Echocardiography In Children With Staphylococcus aureus Bacteremia.

The need for echocardiography in pediatric Staphylococcus aureus bacteremia (SAB) remains uncertain. We reviewed 331 pediatric SAB cases. Nine subjects, all with comorbidities, met echocardiogram criteria for infective endocarditis (IE). IE was associated with congenital heart disease and prolonged bacteremia, suggesting that echocardiography is unnecessary in most children with SAB.

Potential of training of anti-Staphylococcus aureus therapeutic phages against Staphylococcus epidermidis multidrug-resistant isolates is restricted by inter- and intra-sequence type specificity.

Phage therapy appears to be a promising approach to tackle multidrug-resistant bacteria, including staphylococci. However, most anti-staphylococcal phages have been characterized in Staphylococcus aureus, while a limited number of studies investigated phage activity against S. epidermidis. We studied the potential of phage training to extend the host range of two types of anti-S. aureus phages against S. epidermidis isolates. The Appelmans protocol was applied to a mixture of Kayvirus and a mixture of Silviavirus phages repeatedly exposed to seven S. epidermidis strains representative of nosocomial-associated sequence types (ST), including the world-wide disseminated ST2. We observed increased activity only for the Kayvirus mixture against two of these strains (ST2 or ST35). Phage subpopulations isolated from the training mixture using these two strains (five/strain) exhibited different evolved phenotypes, active only against their isolation strain or strains of the same ST. Of note, 16/47 ST2 strains were susceptible to one of the groups of trained phages. A comparative genomic analysis of ancestral and trained phage genomes, conducted to identify potential bacterial determinants of such specific activity, found numerous recombination events between two of the three ancestors. However, a small number of trained phage genes had nucleotide sequence modifications impacting the corresponding protein compared to ancestral phages, two to four of them per phage genome being specific of each group of phage subpopulations exhibiting different host range. The results suggest that anti-S. aureus phages can be adapted to S. epidermidis isolates but with inter- and intra-ST specificity.ImportanceS. epidermidis is increasingly recognized as a threat for public health. Its clinical importance is notably related to multidrug resistance. Phage therapy is one of the most promising alternative therapeutic strategies to antibiotics. Nonetheless, only very few phages active against this bacterial species have been described. In the present study, we showed that phage training can be used to extend the host range of polyvalent Kayvirus phages within the Staphylococcus genera to include S. epidermidis species. In the context of rapid development of phage therapy, in vitro forced adaptation of previously characterized phages could be an appealing alternative to fastidious repeated isolation of new phages to improve the therapeutic potential of a phage collection.

Genome-based model for differentiating between infection and carriage Staphylococcus aureus.

Staphylococcus aureus (S. aureus) is a clinically significant opportunistic pathogen, which can colonize multiple body sites in healthy individuals and cause various life-threatening diseases in both children and adults worldwide. The genetic backgrounds of S. aureus that cause infection versus asymptomatic carriage vary widely, but the potential genetic elements (k-mers) associated with S. aureus infection remain unknown, which leads to difficulties in differentiating infection isolates from harmless colonizers. Here, we address the disease-associated k-mers by using a comprehensive genome-wide association study (GWAS) to compare the genetic variation of S. aureus isolates from clinical infection sites (272 isolates) with nasal carriage (240 isolates). This study uncovers consensus evidence that certain k-mers are overrepresented in infection isolates compared with carriage isolates, indicating the presence of specific genetic elements associated with S. aureus infection. Moreover, the random forest (RF) model achieved a classification accuracy of 77% for predicting disease status (infection vs carriage), with 68% accuracy for a single highest-ranked k-mer, providing a simple target for identifying high-risk genotypes. Our findings suggest that the disease-causing S. aureus is a pathogenic subpopulation harboring unique genomic variation that promotes invasion and infection, providing novel targets for clinical interventions. IMPORTANCE: Defining the disease-causing isolates is the first step toward disease control. However, the disease-associated genetic elements of Staphylococcus aureus remain unknown, which leads to difficulties in differentiating infection isolates from harmless carriage isolates. Our comprehensive genome-wide association study (GWAS) found consensus evidence that certain genetic elements are overrepresented among infection isolates than carriage isolates, suggesting that the enrichment of disease-associated elements may promote infection. Notably, a single k-mer predictor achieved a high classification accuracy, which forms the basis for early diagnostics and interventions.

Draft genome sequence of a spa non-typeable Staphylococcus aureus USA300 isolate causing complicated bacteremia.

Spa-typing is a major genetic tool used to distinguish between Staphylococcus aureus strains. Interestingly, although rare, ~1%-2 of isolates are considered Spa-non-typeable . Herein, we present the draft genome sequence of just such a strain, S. aureus TGH1097, a USA300 isolate from a complex bacteremia infection.

A case of multiple cerebral hemorrhages followed by shower emboli.

An 87-year-old woman was admitted to our hospital (day 0) because of acute disorientation caused by multiple acute intracerebral hemorrhages. T2*-weighted magnetic resonance imaging (MRI) at admission revealed multiple subcortical old microbleeds indicative of cerebral amyloid angiopathy. Microbleeds in the right cerebellar hemisphere and acute spotty ischemia in the left cerebellum were also identified. The patient had been afebrile, and blood examinations on day 7 were within normal limits of inflammatory findings without antibiotics. On day 11, she developed a high fever and blood culture was performed. Her fever resolved within 2 days of antibiotic administration, although subsequent findings revealed her blood culture was positive for Staphylococcus aureus. Echocardiogram revealed bacterial vegetation in the mitral valve and moderate mitral regurgitation, with a diagnosis of infectious endocarditis (IE). Follow-up MRI demonstrated multiple spotty acute infarctions and an increased number of microbleeds. The patient may have been infected via peripheral infusions administered during the first few days after admission. However, considering the coexistence of acute hemorrhagic and ischemic lesions on MRI, as well as the acute lesions in the cerebellum, it is possible that IE was already latent on admission, and that the multiple brain hemorrhages might have been caused by IE rather than by cerebral amyloid angiopathy.

Surface Cleaning with a Microfiber Cloth and Water followed by Ultraviolet-C Light Exposure Achieves Non-Inferior Disinfection of a Pathogenic Staphylococcus aureus Strain versus Use of Germicidal Wipes.

BACKGROUND: We hypothesized that ultraviolet-C (UV-C) irradiation (Surfacide, Waukesha, WI) following use of microfiber cloths (Sanny Shop LLC, Longmont, CO) soaked in water would be noninferior to surface disinfection wipes containing a quaternary ammonium compound and alcohol (PDI Healthcare, Woodcliff Lake, NJ) for the pathogenic Staphylococcus aureus (S. aureus) sequence type 5 (ST5). METHODS: This was a randomized laboratory study of disinfection approaches for S. aureus ST5. A total of 270 polycarbonate slides loaded with ST5 were prepared for the standard surface disinfection group (N=18) and water-soaked microfiber cloths and UV-C treatment group (N=144), along with positive and negative microbiological controls. RESULTS: All 18 samples of S. aureus ST5 bacteria treated with standard chemical wipes showed complete disinfection (colony forming units (CFU) = 0). All 144 treatments with water-soaked microfiber wipes followed by UV-C exposure showed complete disinfection (CFU =0) regardless of soiling, height from the floor, or orientation to the emitters. The upper 95% exact one-sided confidence limit for any CFU >0 was 2.1%. DISCUSSION: These data affirm our hypothesis that surface wiping with a damp cloth followed by triangular UV-C irradiation delivery is noninferior to surface disinfection for S. aureus ST5 using germicidal wipes, even when UV-C is compromised by height from the floor and orientation to the emitters and surface disinfection is targeted. CONCLUSION: Removing bioburden with chemical-free microfiber cloths followed by triangular UV-C delivery is a noninferior strategy to targeted surface disinfection with chemical disinfecting wipes for the pathogenic S. aureus ST5 strain in the laboratory setting.

Mechanism of staphylococcal resistance to clinically relevant antibiotics.

Staphylococcus aureus, a notorious pathogen with versatile virulence, poses a significant challenge to current antibiotic treatments due to its ability to develop resistance mechanisms against a variety of clinically relevant antibiotics. In this comprehensive review, we carefully dissect the resistance mechanisms employed by S. aureus against various antibiotics commonly used in clinical settings. The article navigates through intricate molecular pathways, elucidating the mechanisms by which S. aureus evades the therapeutic efficacy of antibiotics, such as ß-lactams, vancomycin, daptomycin, linezolid, etc. Each antibiotic is scrutinised for its mechanism of action, impact on bacterial physiology, and the corresponding resistance strategies adopted by S. aureus. By synthesising the knowledge surrounding these resistance mechanisms, this review aims to serve as a comprehensive resource that provides a foundation for the development of innovative therapeutic strategies and alternative treatments for S. aureus infections. Understanding the evolving landscape of antibiotic resistance is imperative for devising effective countermeasures in the battle against this formidable pathogen.

Staphylococcus aureus major cell division protein FtsZ assembly is inhibited by silibinin, a natural flavonolignan that also blocked bacterial growth and biofilm formation.

The bacterial cell division protein FtsZ has been considered a potential therapeutic target due to its rapid treadmilling that induces cellular wall construction in bacteria. The current study discovered a novel antimicrobial compound, silibinin, a natural flavonolignan and its impact on the recombinant S. aureus FtsZ (SaFtsZ). Silibinin inhibited S. aureus Newman growth in a dose-dependent manner. The IC50 and MIC values for silibinin were 75 µM and 200 µM, respectively. It had no cytotoxicity against HEK293 cells in vitro. Silibinin also enlarged the bacterial cell morphology by ∼40 folds and showed antibiofilm property. It perturbed the S. aureus membrane potential both at IC50 conc. and at MIC conc. Further, it inhibited both the polymerization and GTPase activity of SaFtsZ. It did not inhibit tubulin assembly, a eukaryotic FtsZ homolog. A fluorescence quenching study yielded the Kd value for SaFtsZ-Silibinin interaction and binding stoichiometry 0.857 ± 0.188 µM and 1:1, respectively. Both in silico study and competition assay indicated that silibinin binds at the GTP binding site on SaFtsZ. The Ki value for the silibinin-mediated inhibition of SaFtsZ was 8.8 µM. Therefore, these findings have comprehensively shown the antimicrobial behavior of silibinin on S. aureus Newman cells targeting SaFtsZ.

Occurrence, multidrug resistance and potential risk factors for Staphylococcus aureus infection at worker-animal and working equipment interfaces: a systematic review and meta-analysis of the Ethiopian literature.

Background: Staphylococcus aureus (S. aureus) infecting animals and humans via close contact, handling, or consuming contaminated products is a growing public health concern. In Ethiopia, it is important to examine the overall prevalence of S. aureus, patterns of multidrug resistance, and potential risks in human-animal interface settings. Thus, this review was conducted to estimate the pooled prevalence of S. aureus, its multidrug resistance, and potential risk factors for worker-animal-working equipment interactions. Methods: This systematic review and meta-analysis were carried out by the PRISMA guidelines. The research articles were searched from PubMed, HINARI, Web of Sciences, and Google Scholar databases. Results: This meta-analysis included 13 independent articles and 52 dependent studies. In total, 5,329 humans, 5,475 animals, and 5,119 samples of working equipment were analyzed. The pooled prevalence of S. aureus at the interfaces between humans, animals, and working equipment was 22%, there was a high level of heterogeneity (I2 = 94%: p < 0.01). The overall pooled prevalence of S. aureus in dairy farm sources was 23% (95% CI, 17-30%) compared to 18% in abattoirs. The pooled prevalence of S. aureus was estimated to be 25% for human sources, 23% for animal sources, and 19% for working equipment. The total multidrug resistance (MDR) rate was 27%. The present study illustrates that a predominant antimicrobials comprising ampicillin, penicillin, chloramphenicol, tetracycline, and ciprofloxacin, accounts for the development of resistance in S. aureus strains, with a prevalence of 72%. According to the qualitative assessment of potential risk factors, animal age, worker education, lactation stage, and hand washing by milkers influenced the circulation of S. aureus at animal-worker and working equipment interfaces. Conclusion: The pooled prevalence of S. aureus at the interface of human,-and animal-working equipment was quantified at 22%. S. aureus was found in humans, animals, and equipment at nearly the same rate. The results of this study demonstrate that S. aureus is hazardous and circulates among animals, workers, and equipment: farmers, animal owners, employees, and the public need to be educated about S. aureus. Moreover, animals and work equipment should be included in the control and prevention of S. aureus infection.

Clinical profile, microbiology and outcomes in infective endocarditis treated with aortic valve replacement: a multicenter case-control study.

BACKGROUND: Aortic valve infective endocarditis (IE) is associated with significant morbidity and mortality. We aimed to describe the clinical profile, risk factors and predictors of short- and long-term mortality in patients with aortic valve IE treated with aortic valve replacement (AVR) compared with a control group undergoing AVR for non-infectious valvular heart disease. METHODS: Between January 2008 and December 2013, a total of 170 cases with IE treated with AVR (exposed cohort) and 677 randomly selected non-infectious AVR-treated patients with degenerative aortic valve disease (controls) were recruited from three tertiary hospitals with cardiothoracic facilities across Scandinavia. Crude and adjusted hazard ratios (HR) were estimated using Cox regression models. RESULTS: The mean age of the IE cohort was 58.5 ± 15.1 years (80.0% men). During a mean follow-up of 7.8 years (IQR 5.1-10.8 years), 373 (44.0%) deaths occurred: 81 (47.6%) in the IE group and 292 (43.1%) among controls. Independent risk factors associated with IE were male gender, previous heart surgery, underweight, positive hepatitis C serology, renal failure, previous wound infection and dental treatment (all p < 0.05). IE was associated with an increased risk of both short-term (≤ 30 days) (HR 2.86, [1.36-5.98], p = 0.005) and long-term mortality (HR 2.03, [1.43-2.88], p < 0.001). In patients with IE, chronic obstructive pulmonary disease (HR 2.13), underweight (HR 4.47), renal failure (HR 2.05), concomitant mitral valve involvement (HR 2.37) and mediastinitis (HR 3.98) were independent predictors of long-term mortality. Staphylococcus aureus was the most prevalent microbe (21.8%) and associated with a 5.2-fold increased risk of early mortality, while enterococci were associated with the risk of long-term mortality (HR 1.78). CONCLUSIONS: In this multicenter case-control study, IE was associated with an increased risk of both short- and long-term mortality compared to controls. Efforts should be made to identify, and timely treat modifiable risk factors associated with contracting IE, and mitigate the predictors of poor survival in IE.