RESUMEN
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.
RESUMEN
OBJECTIVE: The purpose of this study is a new update on the resistance profile, Macrolide-Lincosamide-Streptogramin B resistance mechanisms and biofilm formation in the Staphylococcus aureus isolated from health care workers (HCWs) nasal carriage at a children's teaching hospital in Babol (Northern Iran). RESULTS: A total of 143 non-repetitive nasal swab samples were collected from volunteers, where 53.8% (n; 77/143) were HCWs, 33.6% (n; 48/143) medical students, and 12.6% (n; 18/143) resident students. The prevalence of nasal carriers of S. aureus was 22.4% (n; 32/143), among them, 40.6% (n; 13/32) were identified as methicillin-resistant Staphylococcus aureus (MRSA( carriers. Antimicrobial susceptibility testing showed that erythromycin (68.8%, n; 22/32) and ciprofloxacin (15.6%, n; 5/32) had the highest and lowest resistance rate, respectively. The frequency of resistance genes in the strains was as follows; ermC (n; 17/32, 53.1%), ermA (n; 11/32, 34.4%), ermB (n; 6/32, 18.7%), ereA (n; 3/32, 9.4%). Moreover, 50.0% (n; 16/32), 28.1% (n; 9/32) and 21.8% (n; 7/32) of isolates were strongly, weakly and moderately biofilm producer, respectively. Macrolides-lincosamides-streptogramins B (MLSB) antibiotic resistance among S. aureus isolates from HCWs nasal carriage have found significant prevalence rates throughout the globe. It is crucial to remember that the development of biofilms and MLS B antibiotic resistance are both dynamic processes.
Asunto(s)
Antibacterianos , Biopelículas , Portador Sano , Clindamicina , Personal de Salud , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas , Staphylococcus aureus , Humanos , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Clindamicina/farmacología , Antibacterianos/farmacología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificación , Staphylococcus aureus/fisiología , Staphylococcus aureus/genética , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/fisiología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/epidemiología , Portador Sano/microbiología , Irán , Masculino , Adulto , Femenino , Eritromicina/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Farmacorresistencia Bacteriana/genéticaRESUMEN
Introduction: Staphylococcus aureus is a prominent cause of postoperative infections, often persisting within host cells, leading to chronic infections. Conventional antibiotics struggle to eliminate intracellular S. aureus due to poor cell penetration. Antimicrobial peptides are a new hope for tackling intracellular bacteria. Accordingly, this study examines the antimicrobial peptide MDP1, derived from melittin, for its efficacy against intracellular S. aureus. Methods: In this study, the physiochemical properties (Prediction of three-dimensional structure, circular dichroism and helical wheel projection analysis) were investigated. Extracellular antibacterial activity and cytotoxicity of MDP1 were also assessed. The mechanism of interaction of MDP1 with S. aureus was evaluated by molecular dynamic simulation, atomic force and confocal microscopy. Bacterial internalization into an endothelial cell model was confirmed through culture and transmission electron microscopy. The effect of the peptide on intracellular bacteria was investigated by culture and epi-fluorescence microscopy. Results and discussion: 3D structural prediction proved the conformation of MDP1 as an α-helix peptide. Helical-wheel projection analysis indicated the proper orientation of hydrophobic amino acid residues for membrane interaction. CD spectroscopy of MDP1 showed that MDP1 in SDS 10 and 30 mM adopted 87 and 91% helical conformation. Atomic force and confocal microscopy assessments as well as molecular dynamics studies revealed the peptide-bacterial membrane interaction. MDP1, at the concentration of 0.32 µg mL-1, demonstrated a fold reduction of 21.7 ± 1.8, 1.7 ± 0.2, and 7.3 ± 0.8 in intracellular bacterial load for ATCC, VRSA, and MRSA, respectively. Molecular dynamics results demonstrate a preferential interaction of MDP1 with POPG/POPE membranes, primarily driven by electrostatic forces and hydrogen bonding. In POPC systems, two out of four MDP1 interacted effectively, while all four MDP1 engaged with POPG/POPE membranes. Gathering all data together, MDP1 is efficacious in the reduction of intracellular VRSA and MRSA proved by culture and epi-fluorescent microscopy although further studies should be performed to increase the intracellular activity of MDP1.
RESUMEN
Staphylococcus aureus (S. aureus), commonly found on the skin and nose, causes minor skin conditions to life-threatening diseases, including boils or impetigo, pneumonia, and bloodstream infections. MRSA (Methicillin-Resistant S. aureus) is a strain resistant to many antibiotics and poses a significant challenge in clinical settings. Nowadays, the alternative drug Linezolid is used, and it is not clear when MRSA starts resistance to it, necessitating the need for more alternative drugs with the least chance of developing resistance. This study aims to identify a multitargeted drug candidate with better efficacy than Linezolid. We have taken three hydrolase and transferase proteins from S. aureus, performed the multitargeted docking studies with human-approved drugs, and compared them with the control drug Linezolid. The docking and MM\GBSA scores ranging from -6.79 to -5.78 Kcal/mol and - 37.47 to 30.16 Kcal/mol, respectively, that revealed Deprodone (used for inflammatory skin disorders, bowel disease, and fatty acid metabolism disorders) can be a far better and multitargeted drug candidate than Linezolid. We extended our studies to include extensive pharmacokinetics and molecular interaction fingerprints for interaction pattern studies. Also, the DFT computations optimised the drug, and we extended our studies for MD Simulation in water for 100 ns, which showed the complexes among the identified drug with proteins are entirely stable with acceptable deviation, fluctuations and many intermolecular interactions that make them stable. We also performed the MM\GBSA studies on MD simulation's all 1000 frames to understand the complex energy level. All the results reveal promising interactions between Deprodone and the targeted enzymes, suggesting its potential as a multitargeted therapeutic agent-however, experimental studies need to validate Deprodone against MRSA.
RESUMEN
Methicillin-resistant Staphylococcus aureus (MRSA) has been included by the World Health Organization in its list of "priority pathogens" because of its widespread prevalence and the severity of the infections it causes. The role of food in infections caused by MRSA is unknown, although strains of this microorganism have been detected in various items for human consumption. In order to gain an overview of any possible role of food in MRSA infections, a review was undertaken of studies published between January 2001 and February 2024 relating to MRSA. These comprised research that focused on fish and shellfish, eggs and egg products, foods of vegetable origin, other foodstuffs (e.g., honey or edible insects), and drinking water. In most of these investigations, no prior enrichment was carried out when isolating strains. Three principal methods were used to confirm the presence of MRSA, namely amplification of the mecA gene by PCR, amplification of the mecA and the mecC genes by PCR, and disc diffusion techniques testing susceptibility to cefoxitin (30 µg) and oxacillin (1 µg). The great diversity of methods used for the determination of MRSA in foods and water makes comparison between these research works difficult. The prevalence of MRSA varied according to the food type considered, ranging between 0.0% and 100% (average 11.7 ± 20.3%) for fish and shellfish samples, between 0.0% and 11.0% (average 1.2 ± 3.5%) for egg and egg products, between 0.0% and 20.8% (average 2.5 ± 6.8%) for foods of vegetable origin, between 0.6% and 29.5% (average 28.2 ± 30.3%) for other foodstuffs, and between 0.0% and 36.7% (average 17.0 ± 14.0%) for drinking water.
RESUMEN
Antibiotic resistance poses a persistent threat to modern medicine due to the emergence of novel antibiotic-resistant strains. Therefore, a timely understanding of antibiotic resistance and the virulence biology of pathogenic bacteria, particularly those of public health significance, is crucial for implementing effective mitigation strategies. This study aimed to investigate the virulence profiles of ten S. aureus isolates (NDa to NDj) and ten E. coli isolates (ND1 to ND10) originating from livestock and poultry, and to assess how various cell surface properties and biofilm formation abilities influence antibiotic resistance phenotypes. Antibiotic resistance profiling through phenotypic (AST) and genotypic methods (PCR) confirmed that NDa to NDe were methicillin-resistant S. aureus (MRSA) and ND1 to ND5 were extended-spectrum ß-lactamase (ESBL) producing E. coli isolates. Virulence properties such as hemolytic activity, coagulase activity, and nuclease activity were found to be independent of the antibiotic resistance phenotype in S. aureus. In contrast, biofilm formation phenotype was observed to influence antibiotic resistance phenotypes, with MRSA and ESBL E. coli isolates demonstrating higher biofilm formation potency. Chemical and enzymatic analysis of S. aureus and E. coli biofilms revealed proteins and polysaccharides as major components, followed by nucleic acids. Furthermore, cell surface properties such as auto-aggregation and hydrophobicity were notably higher in isolates with strong to medium biofilm-forming capabilities (ESBL and MRSA isolates), corroborated by genomic confirmation of various genes associated with biofilm, adhesion, and colonization. In conclusion, this study highlights that surface hydrophobicity and biofilm formation ability of MRSA (NDa to NDe) and ESBL E. coli (ND1 to ND5) isolates may influence antibiotic resistance phenotypes.
Asunto(s)
Antibacterianos , Biopelículas , Escherichia coli , Ganado , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Aves de Corral , Factores de Virulencia , beta-Lactamasas , Biopelículas/crecimiento & desarrollo , Biopelículas/efectos de los fármacos , Animales , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/patogenicidad , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Staphylococcus aureus Resistente a Meticilina/enzimología , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Aves de Corral/microbiología , Factores de Virulencia/genética , Factores de Virulencia/metabolismo , Ganado/microbiología , Virulencia , Antibacterianos/farmacología , Propiedades de Superficie , Genotipo , Fenotipo , Infecciones Estafilocócicas/microbiologíaRESUMEN
Avian arthritis is a common disease in the poultry industry, and the etiology is complex. Bacterial arthritis is usually caused by Staphylococcus aureus (S. aureus) infection. This study explored the minimum inhibitory concentration (MIC) of different organic acids against S. aureus MRSA85 and found that vanillic acid, suberic acid, itaconic acid, salicylic acid, and other organic acids had significant inhibitory effects on this strain, especially cinnamic acid, which exhibited the best inhibitory effect. The Fractional Inhibitory Concentration Index (FICI) test further revealed the synergistic effect among some compound organic acids, which can significantly enhance the antibacterial efficiency against MRSA85 while reducing the risk of bacterial resistance. Under the low concentrations (1/2 or 1/4 MIC) conditions, the MIC of the compound organic acids against S. aureus remains unchanged, and it can even enhance the sensitivity of antibiotic-resistant S. aureus to Oxacillin. Furthermore, the compound organic acids could effectively promote the recovery of S. aureus-induced arthritis in broiler models, reduce inflammatory responses, and lower down bacterial loads and inflammatory cytokine levels in joints, which indicated that the effects of the Compound 2 is comparable to that of the trimethoprim-sulfamethoxazole group. These results support the potential and application value of organic acids and their compounds, including Compound 1 to 3, as novel antibacterial agents in the treatment of S. aureus infections.
RESUMEN
Plant natural products offer promise in combating multi-drug resistance by acting as antibacterial agents through various mechanisms. A metabolomic-guided phytochemical investigation, based on a LC-HRMS/MS and Molecular Networking combined approach, was carried out on an extract of M. alba L. (mulberry) twigs, a common of byproduct of mulberry utilization. Molecular networking uncovered different clusters of prenylated polyphenols, glycosylated phenolic compounds, and Diels-Alder dimers, steering the phytochemical profiling of this extract. This led to the swift annotation and subsequent isolation of 17 secondary metabolites including stilbenoids, flavonoids, and flavanones. Isolated metabolites were tested for their antimicrobial activity against Staphylococcus species. The most active compound resulted to be kuwanon C, exhibiting a MIC value of 8⯵g/mL against the methicillin resistant S. aureus (MRSA) strain and a biofilm producer strain of S. epidermidis. We also observed an interaction between 4⯵g/mL of kuwanon C in combination with low oxacillin dosage against the MRSA. Thanks to the high chemical structure similarity of isolated metabolites, structure-activity relationships of these versatile scaffolds have been postulated.
RESUMEN
Asthma is a chronic respiratory disease that affects children worldwide. Increasing evidence suggests that Staphylococcus aureus contributes to the pathology of asthma. The aim of this study was to evaluate the nasal carriage, antimicrobial susceptibility profile, and presence of enterotoxin genes from S. aureus isolated from children with asthma. Nasal swab samples were collected from 158 children, including 98 children with asthma and 60 healthy controls. S. aureus isolates were identified using phenotypic methods and the presence of the nuc gene. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disc diffusion method. Polymerase chain reaction (PCR) confirmed the presence of the mecA gene and enterotoxin genes. The nuc gene was confirmed in 83 isolates, resulting in a nasal carriage of 52.5% (83/158). The nasal carriage of S. aureus was higher among asthma cases (72.4%), with a significant association of S. aureus nasal carriage observed among asthma cases (OR 0.201, 95% CI 0.063-0.645, p = 0.007). Methicillin-resistant S. aureus (MRSA) nasal carriage was 11.4%. The S. aureus isolates showed high resistance to cefoxitin (99%) and penicillin (92%) but were sensitive to gentamicin (25%). Furthermore, 67.5% of the isolates were multi-drug resistant. The staphylococcal enterotoxin c gene (sec) was the most prevalent enterotoxin (19.7%) among cases and controls. These findings highlight the need for improved antibiotic stewardship in paediatric medicine and implementation of infection control policies. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-024-01272-z.
RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Caryopteris trichosphaera W. W. Sm., a traditional ethnic medicine, was recorded in the Compendium of Materia Medica for treating wound infection by pathogenic infection. However, its antibacterial potential and bioactive compositions against drug-resistant bacteria need to be validated. AIM OF THE STUDY: To investigate the chemical constituents of C. trichosphaera and explore its anti-MRSA component in vitro and in vivo, together with the antibacterial mechanism. MATERIALS AND METHODS: Bioactive constituents investigation was carried out by phytochemical method and antibacterial screening. The antibacterial mechanism was predicted by network pharmacology, which was further validated by time-kill analysis, membrane function tests, multigenerational resistance induction assay and biofilm test, and metabolomics analysis in vitro. In addition, MRSA-induced epidermal infection in mice was selected to evaluate its pharmacological effect in vivo. RESULTS: Six antibacterial diterpenoids against MRSA and VRE with MIC values 4-32 µg/mL from C. trichosphaera were reported for the first time, in which the major compound cativic acid (1) disrupted MRSA cell membranes by modulating permeability, depolarization, and fluidity while increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels. It also displayed remarkable anti-biofilm activity without inducing bacterial resistance or cytotoxicity. Moreover, cativic acid affected MRSA biosynthesis of cofactors, amino acid biosynthesis, nucleotide metabolism by metabolomics analysis. Furthermore, cativic acid accelerated wound healing in MRSA-infected mouse skin wounds, even better than vancomycin. CONCLUSIONS: The results supported the traditional use of C. trichosphaera, and presented unreported anti-MRSA agent, cativic acid, as a plant-derived bactericide in vitro and in vivo for the first time.
RESUMEN
BACKGROUND: Corynebacterium striatum (C. striatum), a common skin and mucosal colonizer, is increasingly considered as an opportunistic pathogen causing bloodstream infections (BSIs). This study aims to investigate the clinical features and outcomes of C. striatum-BSI. METHODS: We included hospitalized cases with C. striatum-positive blood cultures from January 2014 to June 2022 and classified them into C. striatum-BSI group and contamination group; Clinical characteristics, treatments, and outcomes were compared between the C. striatum-BSI group and contamination group, Methicillin-resistant Staphylococcus aureus (MRSA)-BSI and Methicillin-resistant Staphylococcus epidermidis (MRSE)-BSI. RESULTS: Fifty-three patients with positive C. striatum blood cultures were identified. Among them, 25 patients were classified as C. striatum-BSI, with 21 as contamination cases. And 62 cases of MRSA-BSI and 44 cases of MRSE-BSI were identified. Compared to the contaminated group, the C. striatum-BSI group had a shorter time to positivity of blood cultures (27.0 h vs. 42.5 h, P = 0.011). C. striatum-BSI group had a longer time to positivity (27 h) when compared to both the MRSA (20 h) and MRSE groups (19 h) (p < 0.05). Appropriate therapy within 24 h of BSI onset was significantly lower in the C. striatum group (28%) compared to the MRSA (64.5%) and MRSE (65.9%) groups (p < 0.005). The 28-day mortality was higher in the C. striatum group (52.0%) compared to the MRSA (25.8%) and MRSE (18.2%) groups. CONCLUSIONS: Given the distinct characteristics of C. striatum-BSI, including a longer time to positivity than other Gram-positive bacteria and higher mortality rates, we suggest prescribing early appropriate antibiotics if C. striatum-BSI is suspected.
Asunto(s)
Bacteriemia , Infecciones por Corynebacterium , Corynebacterium , Staphylococcus aureus Resistente a Meticilina , Humanos , Corynebacterium/aislamiento & purificación , Corynebacterium/clasificación , Corynebacterium/genética , Masculino , Femenino , Persona de Mediana Edad , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Infecciones por Corynebacterium/microbiología , Infecciones por Corynebacterium/tratamiento farmacológico , Bacteriemia/microbiología , Bacteriemia/tratamiento farmacológico , Bacteriemia/mortalidad , Anciano , Staphylococcus epidermidis/aislamiento & purificación , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/mortalidad , Infecciones Estafilocócicas/tratamiento farmacológico , Adulto , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Estudios Retrospectivos , Anciano de 80 o más AñosRESUMEN
Methicillin-resistant Staphylococcus aureus (MRSA) is a prevalent nosocomial pathogen known for causing severe disseminated infections. Recently, there has been an increase in community-acquired MRSA infections. We present a case of MRSA bacteremia complicated by a cervical epidural abscess. A 63-year-old female with no significant past medical history presented with altered mental status lasting two days. She had recently experienced neck stiffness after lifting a heavy object, initially diagnosed as torticollis, at an outside facility. On examination, she appeared ill and met the criteria for sepsis. Blood cultures confirmed MRSA. She developed hypotension, and an MRI of the brain and cervical spine revealed leptomeningeal enhancement and an epidural abscess. MRSA bacteremia, although common, can manifest in various forms. While it typically occurs in patients with identifiable risk factors, our patient had none. Identifying the source of bacteremia is crucial, as effective treatment requires both source control and antibiotic therapy. Given MRSA's high morbidity and mortality, a thorough and rigorous approach to assessment and management is essential.
RESUMEN
The multi-drug resistance of methicillin-resistant Staphylococcus aureus (MRSA) and complex wound microenvironment challenge the repair of MRSA infected wound. Herein, in this study, α-tocopherol modified glycol chitosan (TG) nanoparticles encapsulated with phytochemical rhein (Rhein@TG NPs) were prepared for comprehensive anti-infection and promotion of MRSA infected wound healing. Rhein@TG NPs could not only specifically release rhein in the infection site in response to low pH and lipase of infectious microenvironment, but also up-regulated M1 macrophage polarization in the infection stage, thus achieving synergistically bacterial elimination with low possibility of developing resistance. Additionally, the NPs reduced the levels of pro-inflammatory factors in the post-infection stage, scavenged the ROS, promoted cell migration and angiogenesis, which significantly improved the microenvironment of infected wound healing. Therefore, this antibiotic-free NPs enabling anti-infection and promotion of wound healing provides a new and long-term strategy for the treatment of MRSA infected wound.
RESUMEN
Frequent occurrence of wound infection caused by multiple-resistant bacteria (MRB) has posed a serious challenge to the current healthcare system relying on antibiotics. The development of novel antimicrobial materials with high safety and efficacy to heal wound infection is of great importance in combating this crisis. Herein, we prepared a promising antibacterial hydrogel by cross-linking ferrous ions (Fe2+) with the deprotonated carboxyl anion in sodium alginate (Na-ALG) to cure wound infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Interestingly, ferrous-modified Na-ALG (Fe-ALG) hydrogel demonstrated better properties compared to the traditional Na-ALG-based hydrogels, including injectability, self-healing, appropriate fluidity, high-water retention, potent MRSA-killing efficacy, and excellent biocompatibility. Importantly, the addition of Fe2+ enhances the antibacterial efficacy of the Na-ALG hydrogel, enabling it to effectively eliminate MRSA and accelerate the healing of antibiotic-resistant bacterial-infected wounds in a remarkably short period (10 days). This modification not only facilitates wound closure and fur generation, but also mitigates systemic inflammation, thereby effectively impeding the spread of MRSA to the lungs. Taken together, Fe-ALG hydrogel is a promising therapeutic material for treating wound infections by Staphylococcus aureus, especially by antibiotic-resistant strains like MRSA.
Asunto(s)
Alginatos , Antibacterianos , Compuestos Ferrosos , Hidrogeles , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Cicatrización de Heridas , Infección de Heridas , Alginatos/química , Alginatos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Compuestos Ferrosos/química , Compuestos Ferrosos/farmacología , Cicatrización de Heridas/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Animales , Infecciones Estafilocócicas/tratamiento farmacológico , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Ratones , Pruebas de Sensibilidad Microbiana , MasculinoRESUMEN
In 2011, a novel methicillin resistance gene, mecC, was described in human and bovine Staphylococcus aureus isolates. mecC-positive S. aureus is most commonly associated with livestock and wildlife populations across Europe and is particularly prevalent in hedgehogs, but only occasionally causes human infections. In this study, we characterize and investigate the origin of two human S. aureus isolates containing mecC genes from New Zealand. The two isolates were identified from patients with severe invasion infections as part of an S. aureus bacteraemia study. Whole-genome sequencing was used to characterize staphylococcal cassette chromosome mec (SCCmec) elements and perform phylogenetic comparisons with publicly available strains from mecC-associated clonal complexes, including isolates from hedgehogs from New Zealand and Europe/United Kingdom (UK), and livestock, wildlife and human isolates from Europe/UK. The two isolates from our study have almost identical SCCmec type XI elements containing a mecC gene. However, this gene contains a premature stop codon, consistent with the methicillin-susceptible phenotype observed for these isolates. Core genome SNP analyses showed that the two isolates are 234 SNPs apart and are most closely related to an isolate obtained from a New Zealand hedgehog. However, there are considerable differences in the mecC mobile element between the human and hedgehog isolates, indicating the presence of an as-yet-unknown reservoir of mecC S. aureus in the New Zealand environment.
RESUMEN
BACKGROUND: Characteristics of non-clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) especially from fishery environment are poorly understood. This research, in addition to comprehensive characterisation, sought to delineate the genetic relatedness between the MRSA strains originating from clinical as well as non-clinical settings. Out of 39 methicillin-resistant staphylococcal isolates from 197 fish samples, 6 (Three each of methicillin-resistant S. haemolyticus (MRSH) and MRSA) with distinct resistance profiles were selected for whole-genome sequencing. Using respective bioinformatics tools, MRSA genomes were comprehensively characterized for resistome, virulomes, molecular epidemiology and phylogenetic analysis. Simultaneously, MRSH genomes were specifically examined to characterize antimicrobial resistance genes (ARGs), owing to the fact that MRSH is often recognized as a reservoir for resistance determinants. RESULTS: Three MRSA clones identified in this study include ST672-IVd/t13599 (sequence type-SCCmec type/spa type), ST88-V/t2526, and ST672-IVa/t1309. Though, the isolates were phenotypically vancomycin-sensitive, five of the six genomes carried vancomycin resistance genes including the VanT (VanG cluster) or VanY (VanM cluster). Among the three MRSA, only one harbored the gene encoding Panton-Valentine Leukocidin (PVL) toxin, while staphylococcal enterotoxin (SEs) genes such as sea and seb, associated with staphylococcal food poisoning were identified in two other MRSA. Genomes of MRSH carried a composite of type V staphylococcal cassette chromosome mec (SCCmec) elements (5C2 & 5). This finding may be explained by the inversion and recombination events that may facilitate the integration of type V elements to the SCC elements of S. aureus with a methicillin-susceptible phenotype. Phylogenetically, MRSA from a non-clinical setting displayed a considerable relatedness to that from clinical settings. CONCLUSION: This study highlights the genetic diversity and resistance profiles of MRSA and MRSH, with non-clinical MRSA showing notable relatedness to clinical strains. Future research should explore resistance gene transfer mechanisms and environmental reservoirs to better manage MRSA spread.
Asunto(s)
Peces , Genoma Bacteriano , Staphylococcus aureus Resistente a Meticilina , Filogenia , Intoxicación Alimentaria Estafilocócica , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Animales , Peces/microbiología , Intoxicación Alimentaria Estafilocócica/microbiología , Genoma Bacteriano/genética , Antibacterianos/farmacología , Secuenciación Completa del Genoma , Virulencia/genética , Pruebas de Sensibilidad Microbiana , Humanos , Factores de Virulencia/genética , Alimentos Marinos/microbiología , Microbiología de Alimentos , Toxinas Bacterianas/genética , Epidemiología Molecular , Staphylococcus haemolyticus/genética , Staphylococcus haemolyticus/efectos de los fármacos , Staphylococcus haemolyticus/aislamiento & purificación , Staphylococcus haemolyticus/patogenicidadRESUMEN
Natural plant extracts have demonstrated significant potential in alternative antibiotic therapies. Cinnamaldehyde (CA) has garnered considerable attention as a natural antibacterial agent. In this study, Tandem mass tag (TMT) quantitative proteomics combined with Western blot and RT-qPCR methods were employed to explore the antibacterial mechanism of CA against Methicillin-Resistant Staphylococcus aureus (MRSA) at the protein level. The results showed that a total of 254 differentially expressed proteins (DEPs) were identified in the control group and CA treatment group, of which 161 were significantly upregulated and 93 were significantly downregulated. DEPs related to nucleotide synthesis, homeostasis of the internal environment, and protein biosynthesis were significantly upregulated, while DEPs involved in the cell wall, cell membrane, and virulence factors were significantly downregulated. The results of GO and KEGG enrichment analyses demonstrated that CA could exert its antibacterial effects by influencing pyruvate metabolism, the tricarboxylic acid (TCA) cycle, teichoic acid biosynthesis, and the Staphylococcus aureus (S. aureus) infection pathway in MRSA. CA significantly inhibited the expression of recombinant protein MgrA (p < 0.05), significantly reduced the mRNA transcription levels of mgrA, hla, and sdrD genes (p < 0.05), and thermostability migration assays demonstrated that CA can directly interact with MgrA protein, thereby inhibiting its activity. These findings suggest that CA exerts its antibacterial mechanism by regulating the expression of related proteins, providing a theoretical basis for further development of clinical applications of antimicrobial agents derived from natural plant essential oils in the treatment of dairy cow mastitis.
RESUMEN
OBJECTIVES: Antimicrobial resistance is a global pandemic that poses a major threat to vision health as ocular bacteria, especially methicillin-resistant S. aureus (MRSA), are becoming increasingly resistant to first-line therapies. Here we evaluated the antimicrobial activity of new synthetic lincosamides in comparison to currently used antibiotics against clinical ocular MRSA isolates. METHODS: Antimicrobial susceptibility testing was performed by broth microdilution for two novel synthetic lincosamides (iboxamycin and cresomycin) and 8 comparator antibiotics against a collection of 50 genomically characterized ocular MRSA isolates, including isolates harboring erm genes (n=25). RESULTS: Both drugs were active against widespread MRSA clonal complexes CC8 and CC5. The MIC50 and MIC90 of iboxamycin were 0.06 mg/L and 2 mg/L respectively. Cresomycin (MIC50â¯=â¯0.06 mg/L) also displayed good activity with an in vitro potency 4-fold higher (MIC90â¯=â¯0.5 mg/L) than iboxamycin. In isolates harboring erm genes, MIC90 were >16, 2 and 0.5 mg/L for clindamycin, iboxamycin and cresomycin, respectively. The in vitro potencies of iboxamycin and cresomycin were similar or higher than that of comparator agents and were not impacted by multidrug resistance phenotypes or by the presence of erm genes when compared to clindamycin. CONCLUSIONS: Our results demonstrate that iboxamycin and cresomycin display potent in vitro activity against ocular MRSA isolates, including multidrug-resistant isolates harboring erm genes.
RESUMEN
BACKGROUND: The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) strains resistant to non-beta-lactam antimicrobials poses a significant challenge in treating severe MRSA bloodstream infections. This study explores resistance development and mechanisms in MRSA isolates, especially after the first dalbavancin-resistant MRSA strain in our hospital in 2016. METHODS: This study investigated 55 MRSA bloodstream isolates (02/2015-02/2021) from the University Hospital of the Medical University of Vienna, Austria. The MICs of dalbavancin, linezolid, and daptomycin were assessed. Two isolates (16-33 and 19-362) resistant to dalbavancin were analyzed via whole-genome sequencing, with morphology evaluated using transmission electron microscopy (TEM). RESULTS: S.aureus BSI strain 19-362 had two novel missense mutations (p.I515M and p.A606D) in the pbp2 gene. Isolate 16-33 had a 534 bp deletion in the DHH domain of GdpP and a SNV in pbp2 (p.G146R). Both strains had mutations in the rpoB gene, but at different positions. TEM revealed significantly thicker cell walls in 16-33 (p < 0.05) compared to 19-362 and dalbavancin-susceptible strains. None of the MRSA isolates showed resistance to linezolid or daptomycin. CONCLUSION: In light of increasing vancomycin resistance reports, continuous surveillance is essential to comprehend the molecular mechanisms of resistance in alternative MRSA treatment options. In this work, two novel missense mutations (p.I515M and p.A606D) in the pbp2 gene were newly identified as possible causes of dalbavancin resistance.
Asunto(s)
Antibacterianos , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Microscopía Electrónica de Transmisión , Infecciones Estafilocócicas , Teicoplanina , Secuenciación Completa del Genoma , Humanos , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Austria/epidemiología , Antibacterianos/farmacología , Teicoplanina/farmacología , Teicoplanina/análogos & derivados , Infecciones Estafilocócicas/microbiología , Daptomicina/farmacología , Mutación , Linezolid/farmacología , Masculino , Mutación Missense , FemeninoRESUMEN
BACKGROUND: Staphylococcus aureus (S. aureus) often colonizes the human skin, upper respiratory and genital tracts. In the female genital tract, it can be passed on to the newborn during vaginal delivery leading to either ordinary colonization, or neonatal infections notably umbilical stump sepsis, scalded skin syndrome, arthritis, or bacteraemia/sepsis. These infections are mediated by staphylococcal virulence factors such as (i) Staphylococcal Enterotoxins A, B, C, D, and E encoded by the sea, seb, sec, sed, see genes, (ii) Exfoliative Toxins A and B encoded by the eta and etb genes, (iii) Toxic Shock Syndrome Toxin 1 (TSST-1) encoded by the tst gene, (iv) Panton-Valentine Leukocidin (PVL) encoded by the pvl gene, and (v) Hemolysins alpha and delta encoded by the hla and hld genes, respectively. We determined the prevalence of S. aureus possessing one or more virulence factor genes and of methicillin resistant Staphylococcus aureus (MRSA) in this population. METHODS: This was a cross-sectional study, which used 85 S. aureus isolates from the Chlorohexidine (CHX) clinical trial study in Uganda. The isolates had been obtained by culturing vaginal swabs (VS) from 1472 women in labour, frozen at minus 80oC, then thawed, sub-cultured, and tested for the selected virulence genes sea, seb, sec, sed, see eta, etb, tst, pvl, hla and hld, and for the methicillin resistance determining gene (mecA). Data were analyzed using SPSS version 20. RESULTS: Of the 85 S. aureus isolates 13 (15.3%) were positive for one or more virulence factor genes, as follows: pvl 9/85 (10.6%), hld 5/85 (5.9%), sea 1/85 (1.2%) and seb genes 1/85 (1.2%). The other virulence genes (sec, sed, see, eta, etb, hla and tst) were not detected in any of the isolates. MRSA was detected in 55.3% (47/85) of the isolates, but only two of these carried the pvl virulence gene. CONCLUSION: This study demonstrated that 15% of the S. aureus colonizing the female lower genital tract of mothers in labour in central Uganda carried one or more virulence genes, mostly pvl, indicating potential for newborn infection with S. aureus acquired in the maternal birth canal. More than half of the isolates were MRSA.