Schematic representation of the mechanisms of antibiotic resistance in S. aureus. (i) Target modification: change in the structure or composition of the target site in a bacterial cell can stop the antibiotic to bind, thus shielding it from the antibiotic. Modification of the bacterial ribosome by 23S ribosomal RNA (rRNA) methyltransferase (encoded by erm genes) leads to a conformational change in the ribosome target [31,32], thereby preventing the binding of erythromycin to the ribosomal

Schematic representation of the mechanisms of antibiotic resistance in S. aureus. (i) Target modification: change in the structure or composition of the target site in a bacterial cell can stop the antibiotic to bind, thus shielding it from the antibiotic. Modification of the bacterial ribosome by 23S ribosomal RNA (rRNA) methyltransferase (encoded by erm genes) leads to a conformational change in the ribosome target [31,32], thereby preventing the binding of erythromycin to the ribosomal

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Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most successful human pathogens with the potential to cause significant morbidity and mortality. MRSA has acquired resistance to almost all β-lactam antibiotics, including the new-generation cephalosporins, and is often also resistant to multiple other antibiotic classes. The expressi...

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... resistance is commonly associated with the acquisition of resistance genes or mutations affecting central biochemical processes. MRSA confers resistance to non-β-lactam antibiotics by various mechanisms, such as (i) target modification, (ii) mutation of target, (iii) drug inactivation by enzymes, and (iv) decreased antibiotic uptake or efflux ( Figure 2). [31,32], thereby preventing the binding of erythromycin to the ribosomal target. ...

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... Most genes encoding toxins are located on mobile genetic elements, 1 including the following representative genes. 2 Encoding mupirocin-acquired resistance (mupA; accession: NG_048008.1), the gene associated with a high-level resistance (minimum inhibitory concentration ≥512 μg/mL) to mupirocin; 3 erythromycin resistance methylase (erm)A and ermC; 4 Panton-Valentine leukocidin (PVL), the leukocidin toxin gene; 5,6 fibronectin binding protein A (fnbA); 7,8 arginine catabolism mobile element (arcA), 9,10 which has the advantage of selective skin colonization); toxic shock syndrome toxin (TSST)-1 gene-encoding TSST, 11 and mecA, related to β-lactam antibiotic resistance. The distribution of toxin genes in the clonal lineages of S. aureus is not random, but phylogenetically characteristic. ...
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Objective To analyze the antibiotic resistance profile, virulence genes, and molecular typing of Staphylococcus aureus (S. aureus) strains isolated in skin and soft tissue infections at the First Affiliated Hospital, Gannan Medical University, to better understand the molecular epidemiological characteristics of S. aureus. Methods In 2023, 65 S. aureus strains were isolated from patients with skin and soft tissue infections. Strain identification and susceptibility tests were performed using VITEK 2 and gram-positive bacteria identification cards. DNA was extracted using a DNA extraction kit, and all genes were amplified using polymerase chain reaction. Multilocus sequence typing (MLST) was used for molecular typing. Results In this study, of the 65 S. aureus strains were tested for their susceptibility to 16 antibiotics, the highest resistance rate to penicillin G was 95.4%. None of the staphylococcal isolates showed resistance to ceftaroline, daptomycin, linezolid, tigecycline, teicoplanin, or vancomycin. fnbA was the most prevalent virulence gene (100%) in S. aureus strains isolated in skin and soft tissue infections, followed by arcA (98.5%). Statistical analyses showed that the resistance rates of methicillin-resistant S. aureus isolates to various antibiotics were significantly higher than those of methicillin-susceptible S. aureus isolates. Fifty sequence types (STs), including 44 new ones, were identified by MLST. Conclusion In this study, the high resistance rate to penicillin G and the high carrying rate of virulence gene fnbA and arcA of S.aureus were determine, and 44 new STs were identified, which may be associated with the geographical location of southern Jiangxi and local trends in antibiotic use. The study of the clonal lineage and evolutionary relationships of S. aureus in these regions may help in understanding the molecular epidemiology and provide the experimental basis for pathogenic bacteria prevention and treatment.
... 7 The MRSA is responsible for 50.00% of deaths 8,9 and it's resistance is mediated by the mecA gene. 10 This gene is acquired through horizontal transfer of the staphylococcal cassette chromosome mec. 11 The mechanism of resistance to methicillin in S. aureus involves the production of PBP2a, having a low affinity to β-lactams. ...
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Staphylococcus aureus is an important pathogen causing a wide range of diseases in both humans and animals. The aim of this research was to screen the vancomycin resistance-associated genes in methicillin-resistant Staphylococcus aureus (MRSA) isolates from animals. A total of 400 nasal swab samples were collected from cattle, goats and sheep between February and August 2022 from both industrial and traditional livestock farms in West Azerbaijan province, Iran. Then, nasal swabs were cultured on mannitol salt agar and molecular analysis was performed after bacteriological examination to confirm the presence of S. aureus. The MecA gene was used to detect MRSA isolates, and two important vancomycin resistance-associated genes, namely vanA and vanB, were searched in the isolates. Out of 400 nasal swabs, 69 samples had S. aureus; of which seven isolates were resistant against methicillin. No vancomycin resistance-associated genes were detected in the MRSA isolates. Based on these findings, vancomycin could be used to treat infections caused by this bacterium.
... Several S. aureus strains have developed resistance against both β-lactam and non-β-lactam antibiotics. Infections due to these strains confer a significant public health threat in the healthcare system [9] . S. aureus acquires multiple genes by mobile genetic elements; the mecA gene responsible for methicillin resistance and SEA and SEG for enterotoxin secretions [10] . ...
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Background: Staphylococcus aureus (S. aureus) is one of the leading causes of skin infections and food poisoning worldwide. Citrus fruits enriched with phytochemicals can exhibit anti-staphylococcal activity. Objective: The study aimed to investigate in vitro susceptibility of citrus fruits against S. aureus harboured enterotoxin genes among food handlers, personnel, and the environment. Methods: S. aureus was isolated from food handlers, personnel, and the environment. Methicillin-Resistant Staphylococcus aureus (MRSA) screening was performed using cefoxitin antibiotic discs. The antimicrobial activity of citrus fruits, including Citrus limon (Lemon), Citrus pseudolimon (galgal), Citrus tangerine (fruiter), Citrus sinensis (malta), and Citrus paradisi (grapefruit), was analyzed by performing well-diffusion assay and broth microdilution method. Genes for toxins production, sea and seg were detected using a Polymerase Chain Reaction (PCR). Results: Out of 200 swab samples, 50 (25%) S. aureus were isolated using the biochemical battery. Antibiotic susceptibility testing (AST) and cefoxitin disc revealed 12 (24%) MRSA strains. Most strains were sensitive to Citrus limon, followed by Citrus pseudolimon, Citrus tangerine, Citrus sinensis, and Citrus paradisi. PCR results detected carriage of the sea gene in 4 (8%) isolates, and 20 (40%) isolates harboured the seg gene. Conclusion: The prevalence of S. aureus, mainly MRSA, was high in the environment. These resistant strains' carriage of sea and sea enterotoxin genes increases their virulence and leads to untreatable infections. The antibacterial activities of citrus fruits should be explored using adavance methods.
... 18 The crux of methicillin resistance lies in the presence of the PBP2a protein, encoded by the "mec" region on chromosomal DNA, which is absent in susceptible strains, rendering most MRSA strains resistant to a broad range of antibiotics. 19,20 Our study specifically targets the methicillin resistance gene mecA, gentamicin resistance gene aacA, and ciprofloxacin resistance genes grlA and grlB in clinical MRSA isolates. The overarching goal is to . ...
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Antibiotic resistance poses a global health crisis, limiting the efficacy of available therapeutic agents and hindering the development of new antibiotics. The pharmaceutical industry's waning interest in antibiotic production further exacerbates this challenge. Addressing antibiotic resistance demands innovative solutions. Here, we explore the application of CRISPR-Cas-based antimicrobials as a pioneering approach to combat multidrug resistance. Our study focuses on the methicillin-resistant clinical Staphylococcus aureus (MRSA), a significant clinical threat. Utilizing CRISPR/Cas9 technology, we aimed to concurrently target methicillin (mecA), gentamicin (aacA), and ciprofloxacin (grlA, grlB) resistance genes, thereby altering the resistance profile and enhancing sensitivity to antibiotics. We engineered CRISPR plasmids containing sgRNAs specific to the target regions, which were subsequently electroporated into MRSA strains. Real-time Polymerase Chain Reaction (RT-PCR) assessed changes in resistance gene expression, while disk diffusion and broth microdilution methods determined alterations in resistance status. Western blotting analyzed changes in PBP2a expression, and Sanger sequence analysis confirmed mutations in target regions. Results revealed a statistically significant 1.5-fold decrease in mecA gene expression, 5.5-fold decrease in grlA gene, 6-fold decrease in grlB gene, and 4-fold decrease in aacA gene compared to the wild type strain, as determined by RT-PCR. Antibiotic susceptibility tests demonstrated the suppression of mecA, grlA, grlB, and aacA genes, resulting in the reversal of resistance to beta-lactam, quinolone, and aminoglycoside antibiotics. Western blot analysis showed 70% decrease in PBP2a expression, indicating the breakdown of beta-lactam resistance. Sanger sequence analysis confirmed point mutations in grlB and aacA genes, along with three-base mutations in grlA and mecA genes. Our findings underscore the potential of CRISPR/Cas9 technology to mitigate antibiotic resistance, offering a transformative strategy to restore the efficacy of existing antibiotics in the face of multidrug-resistant pathogens.
... ureus Rosenbach BAA-44 (Vestergaard et al., 2019). Strain bakteri ini diketahui resisten terhadap antibiotik azitromisin, siprofloksasin, klindamisin, doksisiklin, eritromsin, gentamisin, sefoksitin, penisilin, rifampin, dan tetrasiklin (Song et al., 2020;Lade H., et al., 2022). Studi yang dilakukan di RSUD Dr. Saiful Anwar Malang pada tahun 2010-2014 dilaporkan proporsi MRSA sebesar 38,2%, sedangkan pada tahun 2014 dilaporkan bahwa proporsi MRSA pada pasien infeksi kulit dan jaringan lunak di ruang rawat inap Rumah Sakit Cipto Mangunkusumo sebesar 47% (Nurhasanah & Gultom, 2020). ...
Article
Daun tuba laut (Derris trifoliata Lour.) banyak digunakan masyarakat pesisir pantai utara pulau Jawa sebagai tanaman herbal bermanfaat. Hal ini menarik perhatian banyak peneliti untuk menelaah kandungan senyawa dan aktivitas farmakologi yang dimiliki daun tersebut. Daun tuba laut memiliki aktivitas antibakteri terhadap 25 jenis bakteri patogen. Namun kajian aktvitasnya terhadap bakteri resisten yang salah satunya adalah Methicillin Resistant Staphylococcus aureus (MRSA) ATCC BAA-44 belum dilakukan. Penelitian ini bertujuan untuk mengetahui aktivitas antibakteri ekstrak metanol dan tiga jenis fraksi (air, etil asetat, n-heksan) dari daun tuba laut terhadap MRSA. Ekstraksi dilakukan melalui proses maserasi dan dilanjutkan dengan fraksinasi bertingkat. Skrining aktivitas antibakteri diawali menggunakan metode difusi padat untuk mengamati adanya diameter hambat. Penentuan Konsentrasi Hambat Minimum (KHM) dan Konsentrasi Bunuh Minimum (KBM) dilakukan melalui metode dilusi padat. Ekstrak metanol daun tuba laut menunjukkan adanya aktivitas antibakteri pada kosentrasi 50% (b/v). Sedangkan hasil skrining aktivitas antibakteri pada sampel fraksi teramati adanya zona inhibisi pada fraksi etil asetat dan tidak teramati pada fraksi air ataupun n-heksana. Nilai KHM dan KBM fraksi etil asetat daun tuba laut secara berturut-turut diperoleh sebesar 10 mg/ml dan 15 mg/ml. Kata kunci : aktivitas antibakteri; daun tuba laut; MRSA
... The antimicrobial resistance of S. aureus has been linked to the acquisition of mobile genetic elements (MGE) carrying resistance-encoding genes and mutations affecting the key metabolic processes. These events can lead to various resistance mechanisms, including enzymatic drug inactivation, target modification, the active protection of the target site, and the active efflux of the antimicrobial agent [30][31][32]. ...
... Remarkably, a high proportion of MRSA has acquired resistance to other non-β-lactam agents, including the last resort antimicrobials (glycopeptides, oxazolidinones, and daptomycin), which has crucial implications for the treatment options for this pathogen. Recent reviews on the molecular mechanisms of resistance to non-β-lactam agents are available in the literature [30,31]. ...
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Wounds of an acute or chronic etiology affect millions of people worldwide, with increasing prevalence every year. Microbial infections are one of the main causes that impair the wound healing process, and Staphylococcus aureus, a commensal member of the skin microbiota, is one of the main causative agents of wound infections. Crucially, a high proportion of these infections are caused by methicillin-resistant Staphylococcus aureus, which, in addition to β-lactams, has acquired resistance to almost all the antibacterial agents used to treat it, limiting therapeutic options. Studies on the antimicrobial and healing activities of extracts, essential oils, or metabolites obtained from native plants have been reported in many countries that have a diverse flora and traditions with the use of medicinal plants for the treatment of wound infections. Due to their great chemical diversity, plants have proven to be promising sources of bioactive molecules for the discovery and development of new drugs or strategies for the treatment of wounds. This review highlights the main herbal preparations that have antimicrobial and healing activities with potential for the treatment of wound infections caused by Staphylococcus aureus.
... Although HA-MRSA and CA-MRSA strains may have different antimicrobial susceptibility patterns [15], both are now considered significant hazards to human health in the context of infectious diseases [16]. Understanding their respective distribution in the population is crucial for their treatment and management. ...
... Indeed, different clones (ST239, ST72/IV or ST5/II strains) circulate in different geographic regions [17]. In addition to almost all β-lactams, MRSA strains frequently exhibit resistance to antimicrobial agents from other classes, including erythromycin, azithromycin, lincosamides, gentamicin, amikacin, glycopeptides, oxazolidinones and quinolones [16]. In the present study, resistance to non-β-lactam antibiotics, including gentamicin and erythromycin, was slightly higher in MRSA than in MSSA isolates. ...
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Pyoderma is a common skin infection predominantly caused by Staphylococcus aureus. In addition to methicillin resistance, this pathogen is resistant to many other antibiotics, which ultimately limits the available treatment options. Therefore, the present study aimed to compare the antibiotic-resistance pattern, to detect the mecA gene and the genes encoding microbial surface component recognizing adhesive matrix molecules (MSCRAMMs) in S. aureus isolates. A total of 116 strains were isolated from patients suffering with pyoderma. Disk diffusion assay was opted to perform antimicrobial susceptibility testing of the isolates. Out of the isolates tested, 23–42.2% strains appeared susceptible to benzylpenicillin, cefoxitin, ciprofloxacin and erythromycin. While linezolid was found to be the most effective anti-staphylococcal drug, followed by rifampin, chloramphenicol, clindamycin, gentamicin and ceftaroline. Out of 116 isolates, 73 (62.93%) were methicillin-resistant S. aureus (MRSA). Statistically significant (p ≤ 0.05) differences in antibiotic resistance patterns between MRSA and methicillin-susceptible S. aureus (MSSA) were found. A significant association of resistance to ceftaroline, rifampin, tetracycline, ciprofloxacin, clindamycin, trimethoprim–sulfamethoxazole and chloramphenicol was found in MRSA. However, no significant difference was observed between MRSA and MSSA for resistance against gentamicin, erythromycin or linezolid. All cefoxitin-resistant S. aureus, nonetheless, were positive for the mecA gene. femA was found in all the MRSA isolates. Among other virulence markers, bbp and fnbB were found in all the isolates, while can (98.3%), clfA and fnbA (99.1%) were present predominately in MRSA. Thus, this study offers an understanding of antibiotic resistance MSCRAMMs, mecA, and femA gene patterns in locally isolated strains of S. aureus.
... Collectively, the drug resistance genes identified from our WGS results are consistent with various reported MDR-MRSA isolates that harbored determinants that enhanced their ability to resist antimicrobials [63,64]. These MDR-MRSA harbored blaZ-encoded β-lactamase to disrupt the amide bond of β-lactam ring and different families of exporters including efflux pumps such as NorA, SdrM, and LmrS to extrude drugs (e.g., macrolides, aminoglycosides, oxazolidinones, diaminopyrimidines, and phenicols) from the interior to the external environment, thus lowering their intracellular concentration [65]. ...
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Multidrug resistance (MDR) is a significant challenge in healthcare management, and addressing it requires a comprehensive approach. In this study, we employed a combination of phenotypic and genotypic approaches, along with whole genome sequencing (WGS) to investigate five hospital-associated MDR methicillin-resistant Staphylococcus aureus (MRSA) strains that were isolated from newborn infants. Our analysis revealed the following for the MDR-MRSA strains: SauR31 was resistant to three antimicrobial classes; SauR12, SauR91 and SauR110 were resistant to four antimicrobial classes; and SauR23 exhibited resistance to seven classes. All the MDR-MRSA strains were capable of producing slime and biofilms, harbored SCCmec type IV, and belonged to different spa types (t022, t032, and t548), with varying profiles for microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) and virulence genes. The WGS data for the MDR SauR23 and SauR91 strains revealed that most of the antimicrobial resistance genes were present in the chromosomes, including blaZ, mecA, norA, lmrS, and sdrM, with only the ermC gene found in a small (<3 kb) plasmid. The presence of MDR-MRSA strains among neonates raises public concern, hence implementation of multifaceted interventions is recommended to address this issue. In addition, metadata is needed to improve the investigation of antimicrobial resistance genes in MDR isolates.
... Staphylococcus aureus is a widespread bacterium found in humans and animals [12], in S. aureus, the gene activity that encodes penicillin-binding proteins causes a resistance reaction to beta-lactam antibiotics we know as MRSA [13], additionally resistant to non-beta-lactam medicines are MRSA strains. At first, MRSA was thought to cause nosocomial infections [14]. Nonetheless, MRSA colonization and infection have recently been found in a lot of people and animals who are not in clinical settings [15]. ...
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Methicillin-resistant Staphylococcus aureus (MRSA) is a strain of pathogenic bacteria that is a major problem in the world’s health. Due to their frequent interaction with humans, pets are one of the main risk factors for the spread of MRSA. The possibility for zoonotic transmission exists since frequently kept dogs and cats are prone to contract MRSA and act asreservoirsforspreading MRSA. The mouth, nose, and perineum are the primary locations of MRSA colonization, according to the findings of MRSA identification tests conducted on pets. The types of MRSA clones identi�fied in cats and dogs correlated with MRSA clones infecting humans living in the same geographic area. A significant risk factor for the colonization or transmission of MRSA is human-pet contact. An essential step in preventing the spread of MRSA from humans to animals and from animals to humans is to keep hands, clothing, and floor surfaces clean.
... The first discovered antibiotic was penicillin, and in the year 1940 S. aureus emerged as a clinical issue as a result of developing resistance to penicillin, by creating β-lactamase enzyme that rendered penicillin inactive [13][14][15]. Additionally, the prevalence of MRSA strains that are resistant to a variety of non-β-lactam antibiotics has continuously increased [13]. ...
... In recent years, the frequency of S. aureus mutants resistant to vancomycin has progressively increased [32,33]. The antagonistic effects of mecA and vanA resistance determinants may be the cause of VRSA infections in clinical settings [15,34]. ...
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Citation: Zaher, H.A.; El Baz, S.; Alothaim, A.S.; Alsalamah, S.A.; Alghonaim, M.I.; Alawam, A.S.; Eraqi, M.M. Molecular Basis of Methicillin and Vancomycin Resistance in Staphylococcus aureus from Cattle, Sheep Carcasses and Slaughterhouse Workers. Antibiotics 2023, 12, 205. https://doi. Abstract: Staphylococcus aureus (S. aureus) is a serious infection-causing pathogen in humans and animal. In particular, methicillin-resistant S. aureus (MRSA) is considered one of the major life-threatening pathogens due to its rapid resistance to several antibiotics in clinical practice. MRSA strains have recently been isolated in a number of animals utilized in food production processes, and these species are thought to be the important sources of the spread of infection and disease in both humans and animals. The main objective of the current study was to assess the prevalence of drug-resistant S. aureus, particularly vancomycin-resistant S. aureus (VRSA) and MRSA, by molecular methods. To address this issue, a total of three hundred samples (200 meat samples from cattle and sheep carcasses (100 of each), 50 hand swabs, and 50 stool samples from abattoir workers) were obtained from slaughterhouses in Egypt provinces. In total, 19% S. aureus was isolated by standard culture techniques, and the antibiotic resistance was confirmed genotypically by amplification nucA gen. Characteristic resistance genes were identified by PCR with incidence of 31.5%, 19.3%, 8.7%, and 7% for the mecA, VanA, ermA, and tet L genes, respectively, while the aac6-aph gene was not found in any of the isolates. In this study, the virulence genes responsible for S. aureus' resistance to antibiotics had the highest potential for infection or disease transmission to animal carcasses, slaughterhouse workers, and meat products.