Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Article Types

Countries / Regions

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Search Results (1,220)

Search Parameters:
Keywords = methicillin-resistant S. aureus

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
23 pages, 1584 KB  
Article
Phosphonamidates Integrating Sterically Hindered Phenols with Membrane-Active Cations: A Redox-Activated Approach to Antimicrobial Agents
by Elmira Gibadullina, Adel Shakirov, Margarita Neganova, Yulia Aleksandrova, Alexandra Voloshina, Anna Lyubina, Anastasiya Sapunova, Anna Strelnik, Kamil Ivshin, Assel Shuragaziyeva, Altynkul Toibazarova, Banu Diyarova, Anipa Tapalova, Nurbol Appazov and Alexander Burilov
Int. J. Mol. Sci. 2026, 27(10), 4524; https://doi.org/10.3390/ijms27104524 - 18 May 2026
Abstract
A strategy to create highly effective antimicrobial agents was proposed based on the conjugation of three functional components: a cationic quaternary ammonium salt (QAS) that exerts a membrane-disrupting effect and promotes selective accumulation on bacterial surfaces; a phosphonamidate linker for controlled activation; and [...] Read more.
A strategy to create highly effective antimicrobial agents was proposed based on the conjugation of three functional components: a cationic quaternary ammonium salt (QAS) that exerts a membrane-disrupting effect and promotes selective accumulation on bacterial surfaces; a phosphonamidate linker for controlled activation; and a sterically hindered phenol (SHP) fragment as a potential redox component. This approach enabled the preparation of 40 target phosphonamidate–SHP/QAS hybrids in high yields (88–98%). Evaluation of their antimicrobial activity against major pathogens and methicillin-resistant Staphylococcus aureus (MRSA) revealed high potency against Gram-positive bacteria. The lead compounds achieved minimum inhibitory concentration (MIC) values of 0.7–2.8 μM, which is up to 10 times lower than that of the reference drug, norfloxacin. Mechanistic studies confirmed that these hybrids disrupt the bacterial membrane. In addition, an increase in intracellular ROS levels was observed for the most active compound. The SHP/QAS hybrids retained high activity against S. aureus ATCC 209P after 17 passages and showed low cytotoxicity (SI = 62–92) and negligible hemolysis. These properties indicate that this approach may offer a useful strategy for developing antibacterial agents with a potentially lower risk of inducing conventional resistance mechanisms. Full article
Show Figures

Graphical abstract

28 pages, 1473 KB  
Review
Staphylococcus aureus in Bovine Mastitis: Pathogenesis, Antimicrobial Resistance, and Emerging Control Strategies
by Cosmina Maria Bouari, George Cosmin Nadăş, Smaranda Crăciun and Nicodim Iosif Fiț
Microorganisms 2026, 14(5), 1125; https://doi.org/10.3390/microorganisms14051125 - 15 May 2026
Viewed by 269
Abstract
Bovine mastitis is a major infectious disease in dairy cattle, causing significant economic losses and compromising animal health and milk quality worldwide. Among its etiological agents, Staphylococcus aureus is a key contagious pathogen due to its ability to establish persistent intramammary infections and [...] Read more.
Bovine mastitis is a major infectious disease in dairy cattle, causing significant economic losses and compromising animal health and milk quality worldwide. Among its etiological agents, Staphylococcus aureus is a key contagious pathogen due to its ability to establish persistent intramammary infections and evade host immune responses and antimicrobial therapy. This review summarizes current knowledge on the epidemiology, pathogenesis, clinical presentation, diagnosis, and control of S. aureus in bovine mastitis. Particular emphasis is placed on virulence mechanisms, including adhesion, intracellular persistence, biofilm formation, and immune evasion, which contribute to chronic and recurrent infections. The increasing prevalence of antimicrobial resistance, including methicillin-resistant and multidrug-resistant strains, is highlighted as a major challenge limiting treatment efficacy and posing risks within a One Health context. The review also discusses emerging alternative therapies and innovative control strategies, such as anti-biofilm approaches, immunomodulation, and improved diagnostics, aimed at reducing antimicrobial use. Advances in molecular and point-of-care diagnostic tools are considered for their role in early detection and targeted interventions. Overall, effective control of S. aureus mastitis requires integrated strategies combining prudent antimicrobial use, alternative therapies, improved hygiene, and a multidisciplinary One Health approach. Full article
(This article belongs to the Special Issue Antibiotic Resistance and Alternatives)
Show Figures

Figure 1

23 pages, 2120 KB  
Article
Epidemiological Study of the Relationship Between Antimicrobial Resistance Genes and Biofilm-Forming Capacity in Pathogens Causing Chronic Wound Infections
by Silvia Ioana Musuroi, Adela Voinescu, Corina Musuroi, Delia Muntean, Florin George Horhat, Luminita Mirela Baditoiu, Oana Izmendi, Andrei Cosnita, Valentin Ordodi, Zorin Crainiceanu, Edward Seclaman and Monica Licker
Microorganisms 2026, 14(5), 1117; https://doi.org/10.3390/microorganisms14051117 - 14 May 2026
Viewed by 197
Abstract
Chronic wounds represent a major complication of underlying conditions such as diabetes mellitus, arterial ischemia, surgical wound and burns. This study aimed at the phenotypic and molecular characterization of antimicrobial resistance for a selection of bacterial isolates, originating from wounds harvested from patients [...] Read more.
Chronic wounds represent a major complication of underlying conditions such as diabetes mellitus, arterial ischemia, surgical wound and burns. This study aimed at the phenotypic and molecular characterization of antimicrobial resistance for a selection of bacterial isolates, originating from wounds harvested from patients hospitalized in the Vascular Surgery and Plastic Surgery wards. The microbiological diagnosis of wound infections was established according to the laboratory’s working protocol. PCR screening of antibiotic resistance genes was performed using a real-time PCR, while the microtiter plate assay was used to determine the biofilm-forming capacity. Testing of biofilm susceptibility to meropenem and amikacin was performed on Calgary biofilm device. Of the 88 bacterial isolates studied, 78.40% were Gram-negative bacilli (GNB)—Klebsiella pneumoniae (K.P), Pseudomonas aeruginosa (P.A), Proteus mirabilis (P.M), Acinetobacter baumannii (A.B), while the remaining 21.60% were Gram-positive cocci (GPC)—Staphylococcus aureus (S.A). All A.B isolates and 92.59% of K.P were carriers of β-lactamase- and carbapenemase-encoding genes, while 57.89% of S. aureus isolates were carriers of mecA (methicillin-resistant). Strong biofilm-forming isolates (B+++) were more frequent in P.A than in K.P (p = 0.002) and P.M (p = 0.02), with a frequency comparable to that of A.B strains (p = 0.212). When analyzing the biofilm reaction to meropenem, a significantly lower susceptibility was detected in the biofilm for K.P isolates, compared to the planktonic ones. Most GNB have been extensively multidrug-resistant, particularly K.P and A.B. Isolates from chronic wounds are major biofilm-formers. A strong and statistically significant association has been identified in the case of K.P and P.M between the presence of resistance genes and the biofilm-forming capacity. These findings highlight the need for a customized therapeutic approach for each chronic wound, considering the mechanisms underlying treatment resistance. These include bacterial virulence factors and the wound microenvironment colonized by the biofilm and the relative contribution of each to the overall resistance profile. Full article
(This article belongs to the Special Issue Bacterial Pathogens: Biofilm Formation and Eradication)
Show Figures

Figure 1

16 pages, 1109 KB  
Article
Silver-Functionalized Silk Fibroin Films: Development and Characterization for Antibacterial Wound Dressings
by Annalia Masi, Rebecca Pellegrino, Federica Paladini and Mauro Pollini
Macromol 2026, 6(2), 29; https://doi.org/10.3390/macromol6020029 - 12 May 2026
Viewed by 163
Abstract
In this work, an in situ UV-assisted photoreduction was used to functionalize silk fibroin films with silver nanoparticles in order to develop antibacterial devices for wound healing applications. The process showed high efficiency (~80%) in terms of reacted silver precursor. The effects of [...] Read more.
In this work, an in situ UV-assisted photoreduction was used to functionalize silk fibroin films with silver nanoparticles in order to develop antibacterial devices for wound healing applications. The process showed high efficiency (~80%) in terms of reacted silver precursor. The effects of the silver treatment on fibroin macromolecule were evaluated in function of the process parameters in terms of chemical structure, thermal and mechanical properties, swelling behavior, resistance to degradation and antibacterial activity. Silver functionalization significantly improved the mechanical properties of the films, with Young’s modulus increasing from 0.23 ± 0.04 MPa (methanol-treated samples) to 7.26 ± 0.46 MPa (silver-functionalized samples). In parallel, a marked reduction in swelling degree was observed (from ~360–420% to ~60%), indicating enhanced structural stability. The treated films also exhibited improved resistance to degradation over 7 days under physiological conditions. From a functional perspective, the materials showed strong antibacterial activity, with up to 97–98% reduction in bacterial proliferation for Pseudomonas aeruginosa and Escherichia coli, and up to 93% for methicillin-resistant Staphylococcus aureus. Overall, the results demonstrate that silver functionalization process improves the structural stability of silk fibroin while conferring sustained antibacterial activity, thus supporting their potential application as antimicrobial dressings for the treatment of superficial and low-exudate wounds. Full article
Show Figures

Figure 1

14 pages, 257 KB  
Article
Clinical Experience of Ceftaroline Fosamil in Gram-Positive Infective Endocarditis: A Multicenter Real-World Observational Study
by Daniel Arnés-García, Jorge Calderón-Parra, Marina Calvo-Salvador, Carmen Herrero-Rodríguez, Svetlana Sadyrbaeva-Dolgova and Carmen Hidalgo-Tenorio
Antibiotics 2026, 15(5), 466; https://doi.org/10.3390/antibiotics15050466 - 5 May 2026
Viewed by 295
Abstract
Background/Objectives: Ceftaroline fosamil (CFT) is a fifth-generation cephalosporin approved in Spain for skin and soft tissue infections and community-acquired pneumonia. CFT may also be useful against endovascular infections. This real-world study aimed to evaluate its effectiveness and safety in patients with Gram-positive (GP) [...] Read more.
Background/Objectives: Ceftaroline fosamil (CFT) is a fifth-generation cephalosporin approved in Spain for skin and soft tissue infections and community-acquired pneumonia. CFT may also be useful against endovascular infections. This real-world study aimed to evaluate its effectiveness and safety in patients with Gram-positive (GP) infective endocarditis (IE). Methods: This observational, retrospective multicenter study enrolled adults with GP-IE treated with CFT for ≥48 h. Recruitment extended from CFT incorporation in participating hospitals through May 2024. Data were gathered on demographic, clinical, and microbiological variables, adverse effects, overall and IE-related mortality, relapses, and a composite unfavorable outcome. Results: Seventy-six patients (65.8% male) were enrolled, with a mean age of 68.9 ± 12.8 years and an age-adjusted Charlson index of 4; 55.3% had previous moderate/severe valvular heart disease, 35.5% had atrial fibrillation, 34.2% chronic heart failure, 17.1% chronic kidney disease, and 22.4% septic shock. IE was native valve-related in 53.9%, involving the aortic valve in 38.2% and the mitral in 30.3%. Staphylococcus aureus was isolated in 48.7%, being methicillin-resistant in 40.5% of cases. CFT was salvage therapy in 65.8% and combined with other antibiotics in 94.7%. Valve replacement was indicated in 64.5% but performed in only 67.3% of these. At six months, the adverse effect rate was 9.2%, overall crude mortality 38.2%, infection-related mortality 28.9%, and composite unfavorable outcome 40.1%. In multivariate analysis, mortality-related factors were age-adjusted Charlson index, septic shock, and methicillin-sensitive S. aureus. Conclusions: CFT showed favorable outcomes and acceptable safety in the real-life treatment of GP-related IE in clinically complex patients with high comorbidity and previous antibiotic therapy failures. Full article
(This article belongs to the Section Novel Antimicrobial Agents)
Show Figures

Graphical abstract

12 pages, 3320 KB  
Article
Endophytic Fungi Associated with Plantago major L.: A Source of Bioactive Metabolites with Anti-MRSA Activity
by Phuoc-Vinh Nguyen, Gia Phong Vu, Luyen Tien Vu, Luong Hieu Ngan, Minh-Tri Le, Thu-Hoai Le, Nhat-Thong Le, Linh X. T. Tran and Bac V. G. Nguyen
Appl. Microbiol. 2026, 6(5), 56; https://doi.org/10.3390/applmicrobiol6050056 - 26 Apr 2026
Viewed by 286
Abstract
The rapid emergence of multi-drug resistant (MDR) bacteria has become a major health concern, driving the need to identify new antimicrobial resources. Recently, endophytes, inhabiting in internal tissues of medicinal plants, have drew important interest from the scientific community, as reservoirs of bioactive [...] Read more.
The rapid emergence of multi-drug resistant (MDR) bacteria has become a major health concern, driving the need to identify new antimicrobial resources. Recently, endophytes, inhabiting in internal tissues of medicinal plants, have drew important interest from the scientific community, as reservoirs of bioactive metabolites. Numerous studies highlight the symbiotic relationship between plants and their endophytes, in which these microorganisms produce antimicrobial compounds, helping the host plant’s defense against pathogens. Plantago major (commonly known as plantain) is widely recognized for its therapeutic properties, especially for its antimicrobial properties. In this study, endophytic fungi were isolated from Plantago major, morphologically characterized and identified using ITS sequencing. Their antibacterial activity was assessed using the agar diffusion assay. In total, 21 endophytic fungal isolates were obtained from different plant tissues, including leaves, stems, roots, and flowers. Antibacterial assays against methicillin-resistant Staphylococcus aureus (MRSA) were investigated on PDA, SDA, and CDA media. Amongst the isolates, nine strains (MD-H1, MD-L1, MD-L2, MD-L3, MD-L4, MD-L5, MD-R1, MD-T1, MD-T2, and MD-T10) showed medium to strong antibacterial effects, with inhibition zones exceeding 15 mm. The result suggests that endophytic fungi associated with Plantago is a valuable source of anti-MRSA compounds. Further work will focus on identifying the secondary metabolites responsible for this activity and elucidating their chemical structures, providing a basis for the development of new potent antibiotic agents. Full article
Show Figures

Figure 1

27 pages, 451 KB  
Article
In-Hospital Mortality Predictors and a Bayesian Weighted-Incidence Antibiogram in Infective Endocarditis: A Seven-Year Cohort Study from a Mexican Tertiary University Hospital
by Itzel Elizabeth Garibay-Padilla, Jorge Eduardo Hernandez-Del Río, Dayana Estefania Orozco-Sepulveda, Christian Gonzalez-Padilla, Tomas Miranda-Aquino, Vanessa Salas-Bonales, Judith Carolina De Arcos-Jiménez and Jaime Briseño-Ramírez
Med. Sci. 2026, 14(2), 214; https://doi.org/10.3390/medsci14020214 - 26 Apr 2026
Viewed by 372
Abstract
Background/Objectives: Infective endocarditis (IE) carries substantial mortality, particularly in middle-income settings where patient profiles and microbial ecology differ from those of cohorts used to derive international prognostic scores. Syndrome-specific, locally grounded decision aids for empirical therapy are also scarce. We aimed to identify [...] Read more.
Background/Objectives: Infective endocarditis (IE) carries substantial mortality, particularly in middle-income settings where patient profiles and microbial ecology differ from those of cohorts used to derive international prognostic scores. Syndrome-specific, locally grounded decision aids for empirical therapy are also scarce. We aimed to identify predictors of in-hospital mortality, externally evaluate the RiskE and ICE scores, and construct a Bayesian weighted-incidence syndromic combination antibiogram (WISCA) for IE. Methods: We conducted a retrospective cohort study of consecutive adults with definite or possible IE admitted between January 2019 and January 2026. Candidate predictors were screened in two phases, and a clinically specified model was estimated with maximum-likelihood and Firth penalization, with 1000-replicate bootstrap optimism correction. Calibration was assessed with bootstrap calibration plots and the Hosmer–Lemeshow test. Discrimination was compared against RiskE and ICE using DeLong’s test and reclassification metrics. For empirical coverage, we built a WISCA using identified pathogens, reporting both non-Bayesian bootstrap estimates and Bayesian hierarchical partial-pooling estimates with species- and antibiotic-level random intercepts; analyses were also stratified by IE type. Results: In-hospital mortality was 22.9% in a young cohort (median 37 years) characterized by high hemodialysis prevalence (47.4%), substantial right-sided IE (46.4%), and Staphylococcus aureus predominance (32%) with no methicillin-resistant isolates. Vasopressor-requiring shock (Firth OR 9.23, 95% CI 2.40–40.61) and acute heart failure (OR 10.01, 95% CI 2.78–41.07) were the strongest predictors; the final model achieved an AUC of 0.922 (optimism-corrected 0.908), significantly outperforming RiskE (0.598) and ICE (0.632). The Bayesian WISCA identified multiple carbapenem-sparing and anti-MRSA–sparing regimens with adequate coverage (≥80%), particularly for community-acquired IE, supporting stewardship-oriented empirical selection. Coverage was consistently lower in healthcare-associated IE. Conclusions: A parsimonious three-variable model provided strong, locally valid mortality prediction in this hemodialysis-predominant, MRSA-free cohort, substantially outperforming European-derived scores. External validation in independent cohorts is required before clinical adoption. The Bayesian WISCA demonstrated that adequate empirical coverage is achievable without routine broad-spectrum agents, offering institution-specific guidance for stewardship-compatible regimen selection; multicenter validation is warranted. Full article
(This article belongs to the Section Cardiovascular Disease)
Show Figures

Figure 1

17 pages, 1716 KB  
Article
Genomic Characterization and Virulence Determinants of Staphylococcus aureus Clinical Isolates from Pneumonia Patients in Karaganda, Kazakhstan
by Shynggys Orkara, Vitaliy Strochkov, Alyona Lavrinenko and Nurlan Sandybayev
Antibiotics 2026, 15(5), 431; https://doi.org/10.3390/antibiotics15050431 - 25 Apr 2026
Viewed by 279
Abstract
Background/Objectives: Staphylococcus aureus, particularly methicillin-resistant strains, is a leading cause of severe pneumonia. Understanding local molecular epidemiology, including virulence gene profiles and antimicrobial resistance (AMR) mechanisms, is crucial for effective infection control. This pilot study aimed to characterize S. aureus isolates [...] Read more.
Background/Objectives: Staphylococcus aureus, particularly methicillin-resistant strains, is a leading cause of severe pneumonia. Understanding local molecular epidemiology, including virulence gene profiles and antimicrobial resistance (AMR) mechanisms, is crucial for effective infection control. This pilot study aimed to characterize S. aureus isolates from pneumonia patients in Karaganda, Kazakhstan. Methods: We collected 48 respiratory samples from patients with pneumonia across three medical institutions. Bacterial identification was performed using MALDI-TOF MS. Antimicrobial susceptibility testing (AST) was carried out using European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Whole-genome sequencing of S. aureus isolates was conducted on an Ion Torrent S5 platform. Genomic analysis included multilocus sequence typing (MLST), identification of virulence and AMR genes, and phylogenetic reconstruction. Results: S. aureus was identified in 14.6% (n = 7) of pneumonia cases included in this study. All isolates (100%, n = 7) were phenotypically resistant to benzylpenicillin. The mecA gene was detected in 57.1% of isolates (n = 4), while phenotypic resistance to methicillin was observed in 28.6% (n = 2) of the isolates. Resistance to azithromycin (57.1%, n = 4) and levofloxacin (42.9%, n = 3) was observed among the isolates. Two isolates (28.6%) were multidrug-resistant (MDR). Genomic analysis revealed the prevalence of the ST22 clone (57.1%, n = 4) in the studied cohort. Other sequence types were ST97, ST8, and ST45 (14.3% each). Phylogenetic analysis showed clustering consistent with MLST profiles. All isolates carried a conserved core virulence arsenal, including hemolysin (hla, hlg), biofilm-forming genes (icaADBC), immune evasion genes (sak, scn), and iron acquisition genes (isd). The Panton–Valentine leukocidin (PVL) genes were detected in three isolates. AMR gene analysis revealed the ubiquitous presence of mepA and tetracycline efflux pump genes, along with regulatory genes (arlRS, mepR, mgrA). The blaZ and ermA genes were not detected despite high phenotypic resistance to penicillin and macrolides. Conclusions: This study reports the identification of the virulent and resistant ST22 S. aureus clone in pneumonia cases in Karaganda, Kazakhstan. The discordance between phenotypic and genotypic AMR profiles underscores the necessity for integrated diagnostic approaches. Full article
Show Figures

Figure 1

11 pages, 978 KB  
Article
Application of Long-Read Whole-Genome Sequencing to Clarify Genotypic–Phenotypic Discrepancies in Methicillin-Resistant Staphylococcus aureus
by Jin Ho Jhang, Kwangjin Ahn, Dokyun Kim, Seok Hoon Jeong, Hyun Soo Kim, Young Ree Kim, Young Ah Kim, Kyeong Seob Shin, Jeong Hwan Shin, Jeong Su Park, Kyoung Un Park, Yong Jun Kwon, Soo Hyun Kim, Jong Hee Shin, Soon Young Ahn, Sung Young Lee, Song-mee Bae, Jung Sik Yoo and Young Uh
Diagnostics 2026, 16(8), 1240; https://doi.org/10.3390/diagnostics16081240 - 21 Apr 2026
Viewed by 333
Abstract
Background/Objectives: The Korean Global Antimicrobial Resistance Surveillance System monitors bloodstream Staphylococcus aureus infections by combining antimicrobial susceptibility testing (AST) with conventional polymerase chain reaction (PCR). Considering the clinical significance of methicillin-resistant S. aureus (MRSA), we performed an in-depth analysis of isolates showing [...] Read more.
Background/Objectives: The Korean Global Antimicrobial Resistance Surveillance System monitors bloodstream Staphylococcus aureus infections by combining antimicrobial susceptibility testing (AST) with conventional polymerase chain reaction (PCR). Considering the clinical significance of methicillin-resistant S. aureus (MRSA), we performed an in-depth analysis of isolates showing genotypic–phenotypic discrepancies. Methods: Isolates were collected from designated collection centers in the Republic of Korea between 2017 and 2024. The 30 μg cefoxitin disk diffusion method was used to define the phenotypes. PCR targeting mecA and the staphylococcal cassette chromosome mec (SCCmec) was used to identify genotypes through gel electrophoresis. Long-read whole-genome sequencing (WGS) was performed using the Revio system (Pacific Biosciences) for isolates exhibiting discrepancies between phenotypes and genotypes. Results: In total, 5808 isolates were screened, and seven cases of genotypic–phenotypic discrepancies were identified, including one infant and six elderly patients with chromosomal SCCmec type IV. Although WGS confirmed intact PCR primer-binding sites, structural alterations were observed: three isolates had normal-length mecA and mecR1, two had partial deletions in mecA, and two featured either mecA or mecR1 split into two proteins. Notably, although the six isolates with intact mecR1 genes matched the nucleotide length of SCCmec type IV, their sequences exhibited high homology with SCCmec type II. Conclusions: Despite the presence of mecA, the non-standard configuration of regulatory genes within the SCCmec elements suppressed actual resistance expression. Because conventional PCR focusing on partial gene segments could overlook such phenotypic traits, the meticulous observation and implementation of WGS are crucial for the accurate characterization of genotypic–phenotypic discrepancies. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
Show Figures

Graphical abstract

21 pages, 9972 KB  
Article
Silibinin Potentiates Antimicrobial Action and Reduces Staphyloxanthin in Staphylococcus aureus
by José Lima Pereira-Filho, Amanda Graziela Gonçalves Mendes, Carmem Duarte Lima Campos, Viviane da Silva Sousa Almeida, Aleania Polassa Almeida Pereira, Israel Viegas Moreira, Cinara Regina Aragão Vieira Monteiro, Louriane Nunes Gomes, Cristianne Roberta Rhoden, Antonio José Cantanhede-Filho, Lucilene Amorim Silva, Alberto Jorge Oliveira Lopes, Rafael Cardoso Carvalho and Valério Monteiro-Neto
Pharmaceuticals 2026, 19(4), 643; https://doi.org/10.3390/ph19040643 - 18 Apr 2026
Viewed by 579
Abstract
Background/Objectives: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) necessitates innovative strategies to overcome conventional resistance mechanisms. This study investigated the potential of the natural flavonolignan silibinin (SIL) as an antivirulence agent against S. aureus, with a particular emphasis on its putative multi-target [...] Read more.
Background/Objectives: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) necessitates innovative strategies to overcome conventional resistance mechanisms. This study investigated the potential of the natural flavonolignan silibinin (SIL) as an antivirulence agent against S. aureus, with a particular emphasis on its putative multi-target antibacterial activity and its capacity to potentiate the effects of ciprofloxacin (CIP). Methods: The antibacterial and antivirulence properties of SIL were assessed using both in vitro and in silico approaches. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined, and its synergistic interaction with CIP was evaluated using checkerboard assays. Inhibition of biofilm formation, as well as disruption of established biofilms, was assessed using an MTT-based viability assay. Staphyloxanthin (STX) inhibition was examined through pigment extraction and spectrophotometric quantification of pathway intermediates. Molecular docking studies were conducted to predict the binding affinities of the compounds to key bacterial targets, while safety was evaluated through haemolytic and cytotoxicity assays. Results: SIL exhibited weak to moderate direct antibacterial activity (MICs of 256–512 µg/mL), which is characteristic of many natural product scaffolds. Notably, SIL potentiated the activity of CIP, reducing its MIC by up to fourfold against selected resistant strains of S. aureus. SIL significantly inhibited biofilm formation and disrupted established mature biofilms in a strain-dependent manner. In vitro metabolic profiling and in silico analyses provided mechanistic insights into the effects of SIL on STX biosynthesis. Precursor accumulation data suggest inhibition at the diapophytoene desaturase (CrtN) catalytic step, representing a potential mechanism not previously reported for flavonolignans. Molecular docking studies further predicted favourable binding affinities for CrtM and other key targets. Importantly, SIL exhibited no haemolytic activity and low cytotoxicity in macrophages at synergistic concentrations. Conclusions: This study provides evidence that SIL functions as a dual-action agent, potentiating ciprofloxacin efficacy while reducing STX production and inhibiting biofilm formation, thereby impairing key virulence mechanisms of S. aureus. These findings, together with its favourable safety profile, provide a strong rationale for the development of silibinin-based topical adjuvants to combat drug-resistant Staphylococcus infections in humans. Full article
Show Figures

Graphical abstract

20 pages, 2081 KB  
Review
Penicillin-Binding Protein-4 (PBP4) of Staphylococcus aureus and Its Role in β-Lactam Resistance: An Update
by Nidhi Satishkumar and Som S. Chatterjee
Microorganisms 2026, 14(4), 917; https://doi.org/10.3390/microorganisms14040917 - 18 Apr 2026
Viewed by 517
Abstract
Staphylococcus aureus remains to be one of the leading causes of global mortality. The most common class of antibiotics used to treat S. aureus infections are next-generation β-lactams (NGBs), as they are highly efficacious and have low adverse effects. NGB resistance in S. [...] Read more.
Staphylococcus aureus remains to be one of the leading causes of global mortality. The most common class of antibiotics used to treat S. aureus infections are next-generation β-lactams (NGBs), as they are highly efficacious and have low adverse effects. NGB resistance in S. aureus is classically attributed to penicillin-binding protein-2a (PBP2a), but previous studies from our group have also implicated an altered expression of penicillin-binding protein-4 (PBP4) with NGB resistance. PBP4 is the sole low-molecular-mass (LMM) PBP present in S. aureus; it is also the only known LMM PBP with transpeptidase activity, giving it the unique ability to bring about peptidoglycan cross-linking. In this article, we review some of the recent findings from our group, which reveal that mutations associated with PBP4 lead to altered protein expression and NGB resistance in both methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) backgrounds. We discuss the clinical relevance of PBP4-associated mutations, particularly in methicillin-resistant lacking mec (MRLM) isolates, as well as the synergistic effect of altered PBP4 and GdpP functions. Finally, this review summarizes the potential role played by PBP4 in S. aureus virulence. Together, we highlight the increasing relevance of PBP4 as a mediator of NGB resistance and discuss its potential as an important factor during infection diagnosis and therapy. Full article
(This article belongs to the Section Antimicrobial Agents and Resistance)
Show Figures

Figure 1

18 pages, 3583 KB  
Article
Carbon Dots and Their Functionalization with Photosensitizer Chlorin E6: Advancing Antibacterial Efficacy Through Enhanced Photodynamic Effects
by Siqi Wang, Colin P. McCoy, Peifeng Li, Yining Li, Yinghan Zhao, Gavin P. Andrews and Yi Ge
Pharmaceutics 2026, 18(4), 487; https://doi.org/10.3390/pharmaceutics18040487 - 15 Apr 2026
Viewed by 456
Abstract
Background/Objectives: Carbon dots (CDs) are promising antimicrobial nanomaterials owing to their biocompatibility, environmental friendliness, and tunable surface chemistry. This study aimed to synthesize nitrogen-doped CDs (AS-CDs) and develop a light-responsive antibacterial system through conjugation with chlorin e6 (Ce6). Methods: AS-CDs were [...] Read more.
Background/Objectives: Carbon dots (CDs) are promising antimicrobial nanomaterials owing to their biocompatibility, environmental friendliness, and tunable surface chemistry. This study aimed to synthesize nitrogen-doped CDs (AS-CDs) and develop a light-responsive antibacterial system through conjugation with chlorin e6 (Ce6). Methods: AS-CDs were synthesized by a microwave-assisted method using L-ascorbic acid and spermidine, followed by conjugation with Ce6. The materials were characterized by transmission electron microscopy, zeta potential analysis, and spectroscopic methods, and their antibacterial activity was evaluated against Escherichia coli, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA) under both dark and visible-light conditions. Cytotoxicity was assessed using HaCaT cells. Results: The AS-CDs exhibited a uniform nanoscale morphology with an average diameter of 6.3 nm and a positive surface charge of +15.6 mV, together with intrinsic broad-spectrum antibacterial activity. Ce6 conjugation further enhanced antibacterial efficacy under light irradiation, with the CDs-Ce6 conjugate achieving complete eradication of S. aureus and MRSA and marked inhibition of E. coli at 2.5 μg/mL. Cytotoxicity studies demonstrated low toxicity in HaCaT cells within the effective antibacterial concentration range. Conclusions: These findings highlight the potential of microwave-synthesized, photosensitizer-conjugated CDs as next-generation antimicrobial agents. This platform offers a cost-effective, sustainable, eco-friendly, and efficient platform for combating bacterial infections, with broader potential in pharmaceutical and biomedical applications. Full article
Show Figures

Figure 1

30 pages, 2443 KB  
Article
Ecological Dynamics of Staphylococcus aureus in Raw Ewe Milk Following Different Mastitis Treatment Protocols
by Konstantina Fotou, Georgios Rozos, Konstantina Nikolaou, Vaia Gerokomou, Aikaterini Dadamogia, Sotiria Vouraki, Panagiotis Demertzis, Konstantoula Akrida-Demertzi, Natalia G. C. Vasileiou, Ioannis Skoufos, Athina Tzora and Chrysoula (Chrysa) Voidarou
Antibiotics 2026, 15(4), 388; https://doi.org/10.3390/antibiotics15040388 - 10 Apr 2026
Viewed by 578
Abstract
Background/Objectives: Staphylococcus aureus (S. aureus) intramammary infection remains a major global dairy problem due to its contagious nature, its ability to persist and colonize teat/skin and mucosal niches, and the often-limited bacteriological cure achieved with antimicrobial therapy. Beyond udder health, [...] Read more.
Background/Objectives: Staphylococcus aureus (S. aureus) intramammary infection remains a major global dairy problem due to its contagious nature, its ability to persist and colonize teat/skin and mucosal niches, and the often-limited bacteriological cure achieved with antimicrobial therapy. Beyond udder health, it is relevant to public health because it can enter raw milk chains and serve as a reservoir for antimicrobial resistance determinants that may circulate between dairy animals and humans. Methods: We assessed S. aureus’ ecology in raw ewe milk from 75 sheep farms in Epirus (Greece) by sampling clinically healthy controls (group A) and clinical mastitis cases pre-treatment (group B), followed by resampling at the first post-withdrawal milking after penicillin/streptomycin treatment (group C1—therapeutic protocol 1), oxytetracycline treatment (group C2—therapeutic protocol 2), or enrofloxacin treatment (group C3—therapeutic protocol 3). Results: S. aureus detection was high and comparable across groups (A 23.0%, B 22.0–30.0%, C 20.0–22.0%), and paired analyses showed no significant pre–post shifts in detection/burden within therapeutic protocols (all p > 0.05). Nevertheless, persistence remained evident. The chromosomal gene mecA was detected in S. aureus strains in all groups, ranging from 13.6% in controls to 54.5% post-withdrawal in group C1, and was also present in the pre-treatment group. In paired sampling animals, mecA was mostly stable, with rare emergence or loss. Across antibiotic classes, within-animal resistance transitions were generally uncommon and non-significant (p > 0.05); β-lactam resistance was fully stable (p = 1.00). Descriptively, resistance to protein synthesis inhibitors tended to decline after therapy in protocol 1 and protocol 3, while protocol 3 showed post-treatment gains in fluoroquinolone resistance. By contrast, virulence-associated phenotype traits shifted after therapy: enterotoxigenicity increased post-withdrawal (especially in the C3 group), Staphylococcal Enterotoxin A (SEA) and Staphylococcal Enterotoxin B (SEB) appeared only post-therapy, Staphylococcal Enterotoxin D (SED) increased significantly in paired isolates (p = 0.002), and strong biofilm adherence increased (in C3, p = 1.5 × 10−5). Conclusions: The detection of S. aureus after therapy suggests that one possibility is that antimicrobial exposure may select for, or otherwise reshape, the residual intramammary population, rather than reliably eliminating it—an outcome that remains clinically relevant for udder health. Moreover, the persistence of mecA/methicillin-resistant Staphylococcus aureus (MRSA)-compatible profiles indicates that milk released to the food chain after withdrawal compliance may still harbor S. aureus with enhanced preservation capacity and significant food safety relevance. Full article
Show Figures

Figure 1

10 pages, 221 KB  
Perspective
Epidemiologic and Clinical Divergence of MRSA USA100 and USA300 in the United States
by Camille André and Michael S. Gilmore
Antibiotics 2026, 15(4), 372; https://doi.org/10.3390/antibiotics15040372 - 4 Apr 2026
Viewed by 568
Abstract
Methicillin-resistant S. aureus (MRSA) is listed by the World Health Organization as a priority pathogen posing a major worldwide threat to public health. Two lineages of MRSA predominate as causes of human infections in the U.S.: USA300 and USA100. Although they are most [...] Read more.
Methicillin-resistant S. aureus (MRSA) is listed by the World Health Organization as a priority pathogen posing a major worldwide threat to public health. Two lineages of MRSA predominate as causes of human infections in the U.S.: USA300 and USA100. Although they are most often grouped together as MRSA, these two lineages differ in pathogenetic mechanisms in important ways. The epidemic spread of these two dominant lineages has been problematic because of the multidrug-resistant profile of USA100 and the virulence of USA300, as well as their ability to adapt to both community and hospital environments. In this perspective, we examine what is currently known about their distinctive biology and the consequent differences in infections caused by these two main MRSA epidemic clones. The purpose of this perspective is to provide critical insights to the clinical microbiology community to stimulate further research to inform the design of new prevention and management strategies for MRSA. Full article
15 pages, 2606 KB  
Article
Antibiotic Resistance and Genomic Diversity of Methicillin-Resistant Staphylococcus aureus Clonal Complex 45 Isolates in Kuwait Hospitals
by Samar S. Boswihi, Tina Verghese and Edet E. Udo
Antibiotics 2026, 15(4), 362; https://doi.org/10.3390/antibiotics15040362 - 1 Apr 2026
Viewed by 518
Abstract
Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) causes hospital- and community-acquired infections. MRSA is a highly diverse strain that includes several epidemic clones, including CC45. A previous study conducted among MRSA isolates in Kuwait identified CC45 in two isolates in the early 2000s. This study [...] Read more.
Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) causes hospital- and community-acquired infections. MRSA is a highly diverse strain that includes several epidemic clones, including CC45. A previous study conducted among MRSA isolates in Kuwait identified CC45 in two isolates in the early 2000s. This study provides an update on the prevalence and molecular characteristics of CC45 among MRSA isolates in Kuwait hospitals, during 2016–2022. Methods: A total of 13,276 MRSA isolates were collected during 2016–2022 and typed using antibiogram, DNA microarray, Staphylococcal protein A (spa) typing, pulsed-field gel electrophoresis (PFGE), and multi-locus sequence typing (MLST). Results: CC45 was detected in 87 (0.65%) of the 13,276 MRSA isolates. The isolates were resistant to fusidic acid (n = 71), erythromycin (n = 16), and inducible clindamycin resistance (n = 15). Twenty-one isolates were resistant to multiple antibiotics. Spa typing identified 19 types, with t362 (n = 35) and t132 (n = 27) as the dominant types. DNA microarray identified seven genotypes with CC45-MRSA-[IV + fus] (n = 36) and CC45-MRSA-[VI + fus] (n = 30) as the dominant types. MLST identified six sequence types (STs): ST7119, ST508, ST45, ST46, ST9548, and ST10699. PFGE clustered the isolates into two major types, A and B, with type A being the major type (n = 83), mostly consisting of CC45-MRSA-[IV + fus] isolates. The CC45-MRSA-[IV + fus] and CC45-MRSA-[VI + fus] genotypes were detected throughout the study period (2016–2022), whereas the other genotypes were detected less frequently. Conclusions: The CC45-MRSA circulating in Kuwait hospitals comprises genetically diverse isolates that may have originated from different sources. The emergence of multidrug resistance among the isolates poses challenges for therapy and infection prevention. Full article
(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)
Show Figures

Figure 1

Back to TopTop