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1.
Ann Saudi Med ; 44(2): 67-72, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38615188

RESUMO

BACKGROUND: Inevitably, the floors of mosques are contaminated with microorganisms, and the risk of pathogen transmission is probably high between the many visitors, but the issue has been infrequently studied. OBJECTIVES: Investigate microorganism variety and risk of contamination on commonly used carpets and rosaries (prayer beads). DESIGN: Cross-sectional. SETTINGS: Mosques. METHODS: This study was carried out in three different cities of Turkey in 2023, focusing on mosques located around hospitals. Forty mosques were included in the study and from each mosque 10 samples were collected from various parts of carpets and rosaries. The number of positive culture isolates were identified. MAIN OUTCOME MEASURES: Diversity and distribution of microorganisms isolated from mosque carpets and rosaries; methicillin-resistance rates in Staphylococci. SAMPLE SIZE: 400 samples. RESULTS: Growth was observed in 368 (92%) of 400 samples examined. The microorganisms isolated in the highest number were methicillin-susceptible coagulase negative Staphylococci (MSCoNS) (59.8%), Microcooccus (41%) and diphtheroids (31.3%). The rates of total growth (P=.001), including diphtheroids (P=.018), methicillin-resistant coagulase negative Staphylococci (P=.001), Bacillus spp. (P=.036) and Aspergillus spp. (P=.002) rates were significantly higher in the rosary samples than carpet samples. At mosques in Tokat, a province center, 4 samples were positive for Acinetobacter baumannii, two samples were positive for Pseudomonas aeruginosa and one sample for methicillin-resistant Staphylococcus aureus (MRSA), and these were isolated from rosaries. 0.3% of Staphylococcus isolates were MRSA. CONCLUSION: As there is a high risk of contamination of carpets and prayer beads on the mosque floor with human flora, the use of appropriate hygiene practices is necessary. We also found some emerging bacteria in addition to the normal human flora. LIMITATIONS: Our study was conducted in three provinces. Further studies might cover a wider geography.


Assuntos
Coagulase , Staphylococcus aureus Resistente à Meticilina , Humanos , Estudos Transversais , Pisos e Cobertura de Pisos , Meticilina
2.
Biomed Res Int ; 2024: 5675786, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38623471

RESUMO

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of morbidity and mortality among neonates admitted to neonatal intensive care units (NICUs). The MRSA colonization of neonates, attributed to various sources, including mothers, healthcare workers, and environmental surfaces, can lead to severe infection, prolonged hospital stays, and even death, imposing substantial economic burdens. Given the pressing need to mitigate MRSA spread in these vulnerable environments, further examination of the subject is warranted. This systematic review is aimed at synthesizing available evidence on MRSA carriage proportions among mothers of newborns, healthcare workers, and environmental surfaces in NICUs. Methodology. We included observational studies published in English or French from database inception to March 21, 2023. These studies focused on MRSA in nonoutbreak NICU settings, encompassing healthy neonate mothers and healthcare workers, and environmental surfaces. Literature search involved systematic scanning of databases, including Medline, Embase, Web of Science, Global Health, and Global Index Medicus. The quality of the selected studies was assessed using the Hoy et al. critical appraisal scale. The extracted data were summarized to calculate the pooled proportion of MRSA positives, with a 95% confidence interval (CI) based on the DerSimonian and Laird random-effects model. Results: A total of 1891 articles were retrieved from which 16 studies were selected for inclusion. Most of the studies were from high-income countries. The pooled proportion of MRSA carriage among 821 neonate mothers across four countries was found to be 2.1% (95% CI: 0.3-5.1; I2 = 76.6%, 95% CI: 36.1-91.5). The proportion of MRSA carriage among 909 HCWs in eight countries was determined to be 9.5% (95% CI: 3.1-18.4; I2 = 91.7%, 95% CI: 87.1-94.6). The proportion of MRSA carriage among HCWs was highest in the Western Pacific Region, at 50.00% (95% CI: 23.71-76.29). In environmental specimens from five countries, a pooled proportion of 16.6% (95% CI: 3.5-36.0; I2 = 97.7%, 95% CI: 96.6-98.4) was found to be MRSA-positive. Conclusion: With a significant heterogeneity, our systematic review found high MRSA carriage rates in neonate mothers, healthcare workers, and across various environmental surfaces in NICUs, posing a potential risk of nosocomial infections. Urgent interventions, including regular screening and decolonization of MRSA carriers, reinforcing infection control measures, and enhancing cleaning and disinfection procedures within NICUs, are crucial. This trial is registered with CRD42023407114.


Assuntos
Infecção Hospitalar , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/prevenção & controle , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Pessoal de Saúde , Portador Sadio/prevenção & controle
3.
Vet Med Sci ; 10(3): e1440, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38613443

RESUMO

BACKGROUND: Honey exhibits a broad spectrum of antibacterial activity against Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) ones. Chitosan (Cs) is a mucoadhesive polymer that also has antibacterial properties. Special attention has been paid to the design of polymeric nanoparticles (NPs) as new nano drug delivery systems to overcome bacterial resistance and its problems. OBJECTIVES: The aim of the present study is to synthesize Cs-meropenem NPs with/without honey as an antibiofilm and antibacterial agent to inhibit Staphylococcus aureus. METHODS: This study synthesized meropenem and honey-loaded Cs nanogels and subsequently characterized them by Field Emission Scanning Electron Microscopy (FESEM), Fourier Transform Infrared Spectroscopy (FTIR), and DLS-zeta potential. Using the broth microdilution and crystal violet assays, the antibacterial and antibiofilm activity of meropenem and honey-loaded Cs nanogel, free meropenem, free honey, and free Cs NPs were investigated in vitro against MRSA strains. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) was also used to test the cytotoxicity of several Cs-NPs compound against the HEK-293 regular cell line. RESULTS: The average size of meropenem and honey-Cs-NPs was reported to be 119.885 nm, and encapsulation efficiency was 88.33 ± 0.97 with stability up to 60 days at 4°C. The NPs showed enhanced antibiofilm efficacy against S. aureus at sub-minimum inhibitory concentrations. Additionally, the cytotoxicity of meropenem and honey-encapsulated Cs against the HEK-293 normal cell line was insignificant. CONCLUSIONS: Our findings suggested that meropenem and honey-Cs-NPs might be potential antibacterial and antibiofilm materials.


Assuntos
Anti-Infecciosos , Quitosana , Mel , Staphylococcus aureus Resistente à Meticilina , Nanopartículas , Infecções Estafilocócicas , Animais , Humanos , Meropeném/farmacologia , Staphylococcus aureus , Antibacterianos/farmacologia , Quitosana/farmacologia , Células HEK293 , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Infecções Estafilocócicas/veterinária , Biofilmes
4.
J Med Microbiol ; 73(4)2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38567642

RESUMO

Introduction. Staphylococcus aureus is the leading cause of acute medical implant infections, representing a significant modern medical concern. The success of S. aureus as a pathogen in these cases resides in its arsenal of virulence factors, resistance to multiple antimicrobials, mechanisms of immune modulation, and ability to rapidly form biofilms associated with implant surfaces. S. aureus device-associated, biofilm-mediated infections are often persistent and notoriously difficult to treat, skewing innate immune responses to promote chronic reoccurring infections. While relatively little is known of the role neutrophils play in response to acute S. aureus biofilm infections, these effector cells must be efficiently recruited to sites of infection via directed chemotaxis. Here we investigate the effects of modulating CXC chemokine receptor 2 (CXCR2) activity, predominantly expressed on neutrophils, during S. aureus implant-associated infection.Hypothesis. We hypothesize that modulation of CXCR2 expression and/or signalling activities during S. aureus infection, and thus neutrophil recruitment, extravasation and antimicrobial activity, will affect infection control and bacterial burdens in a mouse model of implant-associated infection.Aim. This investigation aims to elucidate the impact of altered CXCR2 activity during S. aureus biofilm-mediated infection that may help develop a framework for an effective novel strategy to prevent morbidity and mortality associated with implant infections.Methodology. To examine the role of CXCR2 during S. aureus implant infection, we employed a mouse model of indwelling subcutaneous catheter infection using a community-associated methicillin-resistant S. aureus (MRSA) strain. To assess the role of CXCR2 induction or inhibition during infection, treatment groups received daily intraperitoneal doses of either Lipocalin-2 (Lcn2) or AZD5069, respectively. At the end of the study, catheters and surrounding soft tissues were analysed for bacterial burdens and dissemination, and Cxcr2 transcription within the implant-associated tissues was quantified.Results. Mice treated with Lcn2 developed higher bacterial burdens within the soft tissue surrounding the implant site, which was associated with increased Cxcr2 expression. AZD5069 treatment also resulted in increased implant- and tissues-associated bacterial titres, as well as enhanced Cxcr2 expression.Conclusion. Our results demonstrate that CXCR2 plays an essential role in regulating the severity of S. aureus implant-associated infections. Interestingly, however, perturbation of CXCR2 expression or signalling both resulted in enhanced Cxcr2 transcription and elevated implant-associated bacterial burdens. Thus, CXCR2 appears finely tuned to efficiently recruit effector cells and mediate control of S. aureus biofilm-mediated infection.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Pirimidinas , Infecções Estafilocócicas , Sulfonamidas , Camundongos , Animais , Staphylococcus aureus/fisiologia , Staphylococcus aureus Resistente à Meticilina/fisiologia , Receptores de Interleucina-8B/genética , Infecções Estafilocócicas/microbiologia , Biofilmes
5.
Int J Nanomedicine ; 19: 2995-3007, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38559446

RESUMO

Background: In the past decades, antimicrobial resistance (AMR) has been a major threat to global public health. Long-term, chronic otitis media is becoming more challenging to treat, thus the novel antibiotic alternative agents are much needed. Methods: ZnO@TiO2@AMP (ATZ NPs) were synthesized through a solvothermal method and subjected to comprehensive characterization. The in vitro and in vivo antibacterial effect and biocompatibility of ATZ NPs were evaluated. For the antibacterial mechanism exploration, we utilized the Electron Paramagnetic Resonance (EPR) Spectrometer to detect and analyze the hydroxyl radicals produced by ATZ NPs. Results: ATZ NPs exhibited a spherical structure of 99.85 nm, the drug-loading rate for ZnO was 20.73%, and AMP within ATZ NPs was 41.86%. Notably, the Minimum Inhibitory Concentration (MIC) value of ATZ NPs against Staphylococcus aureus (S. aureus), methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus pneumoniae (S. pneumoniae) were 10 µg/mL, and Minimum Bactericidal Concentration (MBC) value of ATZ NPs against S. aureus, and S. pneumoniae were 50 µg/mL. In comparison to the model group, the treatment of otitis media with ATZ NPs significantly reduces inflammatory exudation in the middle ear cavity, with no observable damage to the tympanic membrane. Both in vivo and in vitro toxicity tests indicating the good biocompatibility of ATZ NPs. Moreover, EPR spectroscopy results highlighted the superior ability of ATZ NPs to generate hydroxyl radicals (·OH) compared to ZnO NPs. Conclusion: ATZ NPs exhibited remarkable antibacterial properties both in vivo and in vitro. This innovative application of advanced ATZ NPs, bringing great promise for the treatment of otitis media.


Assuntos
Nanopartículas Metálicas , Staphylococcus aureus Resistente à Meticilina , Otite Média , Infecções Estafilocócicas , Óxido de Zinco , Humanos , Staphylococcus aureus , Radical Hidroxila , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Antibacterianos/farmacologia , Antibacterianos/química , Otite Média/tratamento farmacológico , Testes de Sensibilidade Microbiana , Nanopartículas Metálicas/química
6.
Biomed Res Int ; 2024: 4119960, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38559901

RESUMO

Background: Lactobacillus acidophilus is lactic acid bacteria that produce bacteriocins. Bacteriocins are antimicrobial peptides or proteins that exhibit activity against closely related bacteria. The aim of this study was to determine the effect of L. acidophilus ATCC 4356 bacteriocin against Staphylococcus aureus. Material and Methods. We used four different phenotypic methods for antimicrobial activities against two standard strains: methicillin-resistant S. aureus (MRSA) ATCC 33591 and methicillin-susceptible S. aureus (MSSA) ATCC 25923. The methods were (1) agar well diffusion, (2) overlay soft agar, (3) paper disk, and (4) modification of punch hole. The ammonium sulfate method was used to concentrate crude bacteriocin, and ultrafiltration and dialysis tubes were used to remove ammonium sulfate from the bacteriocins. Each method was repeated in triplicate. Result: L. acidophilus ATCC 4356 showed antimicrobial activity against both MRSA and MSSA standard strains only by the overlay soft agar method and not by the agar well diffusion, punch hole modification, and paper disk methods. No antimicrobial effects were observed in crude bacteriocins concentrated. Conclusion: The growth inhibition of S. aureus in overlay soft agar method may be due to the production of bacteriocin-like substances. The overlay soft agar method is a qualitative test, so there is a need for further study to optimize the conditions for the production of bacteriocin-like substances in the culture supernatant and precise comparison between the inhibitory activity and pheromone secretion of different strains.


Assuntos
Anti-Infecciosos , Bacteriocinas , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Bacteriocinas/metabolismo , Lactobacillus acidophilus , Ágar/metabolismo , Sulfato de Amônio/metabolismo , Sulfato de Amônio/farmacologia , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/metabolismo
7.
Biomed Phys Eng Express ; 10(3)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564254

RESUMO

The high demand for bone grafts has motivated the development of implants with excellent osteogenic activity, whereas the risk of implant-associated infection, particularly given the rise of antimicrobial resistance, has compelled the development of implants with innovative antimicrobial strategies in which a small amount of bactericidal agent can effectively kill a wide range of bacteria. To induce antibacterial property, the surface of Grade-5 bone plate titanium implants used in clinical applications was modified using direct current (DC) sputter coating followed by thermal annealing. The 15 nm silver film-coated implants were thermally annealed in the furnace for 15 min at 750 °C. The modified implant surface's antibacterial efficacy againstEscherichia coli(E. coli),Staphylococcus aureus(S. aureus),Salmonella typhi, andMethicillin-resistant staphylococcus aureusbacteria has been assessed using a colony-forming assay. On the modified implant surface, the growth ofE. coliandS. aureusbacteria is reduced by 99.72%, while highly drug-resistant bacteria are inhibited by 96.59%. The MTT assay was used to assess the cytotoxicity of the modified bone-implant surface against NIH3T3 mouse fibroblast cells. The modified bone-implant surface promoted fibroblast growth and demonstrated good cytocompatibility. Furthermore, the mechanical properties of the implant were not harmed by this novel surface modification method. This method is simple and provides new insight into surface modification of commercial metallic implants to have effective antibacterial properties against various classes of bacteria.


Assuntos
Ligas , Staphylococcus aureus Resistente à Meticilina , Prata , Animais , Camundongos , Titânio , Placas Ósseas , Escherichia coli , Células NIH 3T3 , Staphylococcus aureus , Antibacterianos/farmacologia
8.
BMC Infect Dis ; 24(1): 379, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38584271

RESUMO

BACKGROUND: A major worldwide health issue is the rising frequency of resistance of bacteria.Drug combinations are a winning strategy in fighting resistant bacteria and might help in protecting the existing drugs.Monolaurin is natural compound extracted from coconut oil and has a promising antimicrobial activity against Staphylococcus.aureus. This study aims to examine the efficacy of monolaurin both individually and in combination with ß-lactam antibiotics against Staphylococcus aureus isolates. METHODS: Agar dilution method was used for determination of minimum inhibitory concentration (MIC) of monolaurin against S.aureus isolates. Scanning electron microscope (SEM) was used to detect morphological changes in S.aureus after treatment with monolaurin. Conventional and Real-time Polymerase chain reaction (RT-PCR) were performed to detect of beta-lactamase (blaZ) gene and its expressional levels after monolaurin treatment. Combination therapy of monolaurin and antibiotics was assessed through fractional inhibitory concentration and time-kill method. RESULTS: The antibacterial activity of monolaurin was assessed on 115 S.aureus isolates, the MIC of monolaurin were 250 to 2000 µg/ml. SEM showed cell elongation and swelling in the outer membrane of S.aureus in the prescence of 1xMIC of monolaurin. blaZ gene was found in 73.9% of S.aureus isolates. RT-PCR shows a significant decrease in of blaZ gene expression at 250 and 500 µg/ml of monolaurin. Synergistic effects were detected through FIC method and time killing curve. Combination therapy established a significant reduction on the MIC value. The collective findings from the antibiotic combinations with monolaurin indicated synergism rates ranging from 83.3% to 100%.In time-kill studies, combination of monolaurin and ß-lactam antibiotics produced a synergistic effect. CONCLUSION: This study showed that monolaurin may be a natural antibacterial agent against S. aureus, and may be an outstanding modulator of ß-lactam drugs. The concurrent application of monolaurin and ß-lactam antibiotics, exhibiting synergistic effects against S. aureus in vitro, holds promise as potential candidates for the development of combination therapies that target particularly, patients with bacterial infections that are nearly incurable.


Assuntos
Lauratos , Staphylococcus aureus Resistente à Meticilina , Monoglicerídeos , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , 60693 , Glicerol/farmacologia , Sinergismo Farmacológico , Antibacterianos/farmacologia , Monobactamas/farmacologia , Testes de Sensibilidade Microbiana
9.
Front Cell Infect Microbiol ; 14: 1367938, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590439

RESUMO

The increasing prevalence of antimicrobial-resistant Staphylococcus aureus strains, especially methicillin-resistant S. aureus (MRSA), poses a threat to successful antibiotic treatment. Unsuccessful attempts to develop a vaccine and rising resistance to last-resort antibiotics urge the need for alternative treatments. Host-directed therapy (HDT) targeting critical intracellular stages of S. aureus emerges as a promising alternative, potentially acting synergistically with antibiotics and reducing the risk of de novo drug resistance. We assessed 201 ATP-competitive kinase inhibitors from Published Kinase Inhibitor Sets (PKIS1 and PKIS2) against intracellular MRSA. Seventeen hit compounds were identified, of which the two most effective and well-tolerated hit compounds (i.e., GW633459A and GW296115X) were selected for further analysis. The compounds did not affect planktonic bacterial cultures, while they were active in a range of human cell lines of cervical, skin, lung, breast and monocyte origin, confirming their host-directed mechanisms. GW633459A, structurally related to lapatinib, exhibited an HDT effect on intracellular MRSA independently of its known human epidermal growth factor receptor (EGFR)/(HER) kinase family targets. GW296115X activated adenosine monophosphate-activated protein kinase (AMPK), thereby enhancing bacterial degradation via autophagy. Finally, GW296115X not only reduced MRSA growth in human cells but also improved the survival rates of MRSA-infected zebrafish embryos, highlighting its potential as HDT.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Animais , Staphylococcus aureus , Peixe-Zebra , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/microbiologia , Testes de Sensibilidade Microbiana
10.
Bioorg Chem ; 146: 107318, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38579613

RESUMO

Twenty-seven rosmarinic acid derivatives were synthesized, among which compound RA-N8 exhibited the most potent antibacterial ability. The minimum inhibition concentration of RA-N8 against both S. aureus (ATCC 29213) and MRSA (ATCC BAA41 and ATCC 43300) was found to be 6 µg/mL, and RA-N8 killed E. coli (ATCC 25922) at 3 µg/mL in the presence of polymyxin B nonapeptide (PMBN) which increased the permeability of E. coli. RA-N8 exhibited a weak hemolytic effect at the minimum inhibitory concentration. SYTOX Green assay, SEM, and LIVE/DEAD fluorescence staining assay proved that the mode of action of RA-N8 is targeting bacterial cell membranes. Furthermore, no resistance in wildtype S. aureus developed after incubation with RA-N8 for 20 passages. Cytotoxicity studies further demonstrated that RA-N8 is non-toxic to the human normal cell line (HFF1). RA-N8 also exerted potent inhibitory ability against biofilm formation of S. aureus and even collapsed the shaped biofilm.


Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Humanos , Antibacterianos/química , Staphylococcus aureus , 60556 , Escherichia coli , Relação Estrutura-Atividade , Testes de Sensibilidade Microbiana , Biofilmes
13.
Eur J Med Chem ; 270: 116362, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38574637

RESUMO

Antimicrobial resistance (AMR) represents one of the most challenging global Public Health issues, with an alarmingly increasing rate of attributable mortality. This scenario highlights the urgent need for innovative medicinal strategies showing activity on resistant isolates (especially, carbapenem-resistant Gram-negative bacteria, methicillin-resistant S. aureus, and vancomycin-resistant enterococci) yielding new approaches for the treatment of bacterial infections. We previously reported AlkylGuanidino Ureas (AGUs) with broad-spectrum antibacterial activity and a putative membrane-based mechanism of action. Herein, new tetra- and mono-guanidino derivatives were designed and synthesized to expand the structure-activity relationships (SARs) and, thereby, tested on the same panel of Gram-positive and Gram-negative bacteria. The membrane-active mechanism of selected compounds was then investigated through molecular dynamics (MD) on simulated bacterial membranes. In the end, the newly synthesized series, along with the whole library of compounds (more than 70) developed in the last decade, was tested in combination with subinhibitory concentrations of the last resort antibiotic colistin to assess putative synergistic or additive effects. Moreover, all the AGUs were subjected to cheminformatic and machine learning analyses to gain a deeper knowledge of the key features required for bioactivity.


Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Colistina/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Bactérias , Análise de Dados , Testes de Sensibilidade Microbiana
14.
Emerg Microbes Infect ; 13(1): 2341972, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38597192

RESUMO

Staphylococcus aureus (S. aureus) is a notorious pathogen that cause metastatic or complicated infections. Hypervirulent ST398 clonotype strains, remarkably increased in recent years, dominated Community-associated S. aureus (CA-SA) infections in the past decade in China. Small RNAs like RNAIII have been demonstrated to play important roles in regulating the virulence of S. aureus, however, the regulatory roles played by many of these sRNAs in the ST398 clonotype strains are still unclear. Through transcriptome screening and combined with knockout phenotype analysis, we have identified a highly transcribed sRNA, RSaX28, in the ST398 clonotype strains. Sequence analysis revealed that RSaX28 is highly conserved in the most epidemic clonotypes of S. aureus, but its high transcription level is particularly prominent in the ST398 clonotype strains. Characterization of RSaX28 through RACE and Northern blot revealed its length to be 533nt. RSaX28 is capable of promoting the hemolytic ability, reducing biofilm formation capacity, and enhancing virulence of S. aureus in the in vivo murine infection model. Through IntaRNA prediction and EMSA validation, we found that RSaX28 can specifically interact with RNAIII, promoting its stability and positively regulating the translation of downstream alpha-toxin while inhibiting the translation of Sbi, thereby regulating the virulence and biofilm formation capacity of the ST398 clonotype strains. RSaX28 is an important virulence regulatory factor in the ST398 clonotype S. aureus and represents a potential important target for future treatment and immune intervention against S. aureus infections.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Camundongos , Animais , Staphylococcus aureus/genética , Virulência/genética , RNA Bacteriano/genética , Infecções Estafilocócicas/epidemiologia , Fatores de Virulência/genética , Staphylococcus aureus Resistente à Meticilina/genética
15.
Eur J Med Chem ; 270: 116381, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38604097

RESUMO

The high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) strains and the formation of non-growing, dormant "persisters" subsets help bacteria evade antibiotic treatment and enhance bacterial resistance, which poses a serious threat to human life and health. It is urgent to discover novel antibacterial therapies effective against MRSA persisters. Thymol is a common nutraceutical with weak antibacterial and antitumor activities. A series of Thymol triphenylphosphine (TPP) conjugates (TPP-Thy3) was designed and synthesized. These compounds showed significantly improved inhibitory activity against Gram-positive bacteria compared with Thymol. Among them, Thy3d displayed a low probability of resistance selection and showed excellent biocompatibility. Interestingly, Thy3d elicited a rapid killing effect of MRSA persisters (99.999%) at high concentration. Fluorescence experiments, electron microscopy, molecular dynamics simulation and bilayer experiment confirmed that Thy3d conjugates exerted potent antimicrobial activity by disrupting the integrity of the membrane of bacterial even the persister. Furthermore, Thy3d exhibited considerable efficacy in a mouse model of subcutaneous murine MRSA infection. In summary, TPP-Thy3 conjugates are a series of novel antibacterial agents and could serve as a new therapeutic strategy for combating antibiotic resistance.


Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Compostos Organofosforados , Humanos , Animais , Camundongos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Timol/farmacologia , Testes de Sensibilidade Microbiana , Bactérias
16.
Food Microbiol ; 121: 104531, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38637091

RESUMO

The present study aimed to assess the occurrence and counts of Staphylococcus aureus in Brazilian artisanal cheeses (BAC) produced in five regions of Brazil: Coalho and Manteiga (Northeast region); Colonial and Serrano (South); Caipira (Central-West); Marajó (North); and Minas Artisanal cheeses, from Araxá, Campos das Vertentes, Cerrado, Serro and Canastra microregions (Southeast). The resistance to chlorine-based sanitizers, ability to attach to stainless steel surfaces, and antibiogram profile of a large set of S. aureus strains (n = 585) were assessed. Further, a total of 42 isolates were evaluated for the presence of enterotoxigenic genes (sea, seb, sec, sed, see, seg, sei, sej, and ser) and submitted to typing using pulsed-field gel electrophoresis (PFGE). BAC presented high counts of S. aureus (3.4-6.4 log CFU/g), varying from 25 to 62.5%. From the S. aureus strains (n = 585) assessed, 16% could resist 200 ppm of sodium hypochlorite, whereas 87.6% produced strong ability to attach to stainless steel surfaces, corroborating with S. aureus ability to persist and spread in the environment. Furthermore, the relatively high frequency (80.5%) of multidrug-resistant S. aureus and the presence of enterotoxin genes in 92.6% of the strains is of utmost attention. It reveals the lurking threat of SFP that can survive when conditions are favorable. The presence of enterotoxigenic and antimicrobial-resistant strains of S. aureus in cheese constitutes a potential risk to public health. This result calls for better control of cheese contamination sources, and taking hygienic measures is necessary for food safety. More attention should be paid to animal welfare and hygiene practices in some dairy farms during manufacturing to enhance the microbiological quality of traditional cheese products.


Assuntos
Queijo , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Staphylococcus aureus/genética , Queijo/microbiologia , Brasil , Microbiologia de Alimentos , Aço Inoxidável/análise , Enterotoxinas/genética , Leite/microbiologia
17.
Medicine (Baltimore) ; 103(16): e37860, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640320

RESUMO

Staphylococcus aureus is an important human pathogen that has a major impact on public health. The objective of the present work was to determine the prevalence and the pattern of antibiotic susceptibility in S aureus (MRSA) isolates from the King Khalid University Hospital (KKUH) in Riyadh, Saudi Arabia. The isolates were collected from different body sites of infection and the antibiotic susceptibility was confirmed on the Vitek 2 system. A total of 371 MRSA isolates from clinical samples were received over a 12-month period from January 2021 to December 2021. The results showed that infection was predominant among males (55.8%) and most of the isolates occurred in the older age groups, with a mean age of 43.7 years and an age span from <1 to 89 years old. The majority (34.5%) recovered from wound infection followed by (14.6%) from blood. We have observed peaks of MRSA infections during the autumn, especially in September and November. All MRSA isolates were resistant to Amoxicillin + clavulanic acid, Ampicillin, Imipenem, Oxacillin, Cloxacillin, and Penicillin while all isolates were sensitive to Daptomycin and Nitrofurantoin. Furthermore, Vancomycin was resistant in (0.3%) of MRSA isolates, and (2.9%) was resistant to Linezolid. The current study concluded that MRSA strains had developed resistance toward 24 tested antibiotics, including the previous effective drugs vancomycin and linezolid. Therefore, there is an urgent need for continuous review of infection control practices to prevent any further spread of resistant strains.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Masculino , Humanos , Idoso , Adulto , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Vancomicina/farmacologia , Linezolida/farmacologia , Arábia Saudita/epidemiologia , Centros de Atenção Terciária , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Staphylococcus aureus , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Combinação Amoxicilina e Clavulanato de Potássio/farmacologia
18.
Ital J Pediatr ; 50(1): 78, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641615

RESUMO

BACKGROUND: Preterms are at risk of systemic infections as the barrier function of their immature skin is insufficient. The long period of hospitalization and the huge number of invasive procedures represent a risk factor for complications. Among the nosocomial infections of the skin, methicillin-resistant Staphylococcus aureus (MRSA) is associated with significant morbidity and mortality. We report a clinical case of cellulitis and abscess in two preterm twins caused by MRSA in a tertiary level Neonatal Intensive Care Unit (NICU). CASE PRESENTATION: Two preterm female babies developed cellulitis from MRSA within the first month of extrauterine life. The first one (BW 990 g) showed signs of clinical instability 4 days before the detection of a hyperaemic and painful mass on the thorax. The second one (BW 1240 g) showed signs of clinical instability contextually to the detection of an erythematous, oedematous and painful area in the right submandibular space. In both cases the diagnosis of cellulitis was confirmed by ultrasound. A broad spectrum, multidrug antimicrobial therapy was administered till complete resolution. CONCLUSIONS: Due to the characteristic antibiotic resistance of MRSA and the potential complications of those infections in such delicate patients, basic prevention measures still represent the key to avoid the spreading of neonatal MRSA infections in NICUs, which include hand hygiene and strict precautions, as well as screening of patients for MRSA on admission and during hospital stay, routine prophylactic topical antibiotic of patients, enhanced environmental cleaning, cohorting and isolation of positive patients, barrier precautions, avoidance of ward crowding, and, in some units, surveillance, education and decolonization of healthcare workers and visiting parents.


Assuntos
Infecção Hospitalar , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Recém-Nascido , Humanos , Feminino , Controle de Infecções/métodos , Celulite (Flegmão) , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Infecção Hospitalar/prevenção & controle , Unidades de Terapia Intensiva Neonatal
19.
ACS Appl Mater Interfaces ; 16(15): 18400-18410, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38576193

RESUMO

Drug-resistant bacterial infection and biofilm formation are the key inhibitors of wound healing, and new strategies are urgently needed to address these issues. In this study, we designed a pH-responsive co-assembled peptide hydrogel to inhibit Methicillin-resistant Staphylococcus aureus (MRSA) infection and promote wound healing. We synthesized a cationic short peptide (Nap-FFKKK) and a co-assembled hydrogel with curcumin at pH ∼ 7.8. The loaded curcumin was continuously released in a weak acid environment (pH ∼ 5.5). The lysine-rich cationic peptide inhibited biofilm formation in MRSA via electrostatic interaction with the negatively charged bacterial cell surface and, thus, provided a reinforcing antibacterial effect with curcumin. In vitro antibacterial experiments showed that the co-assembled system considerably reduced the minimum inhibitory concentration of curcumin against MRSA by 10-fold and promoted wound healing in a mouse model of MRSA-infected wounds. This study provides a simple and promising strategy to treat drug-resistant bacterial infections in wounds.


Assuntos
Infecções Bacterianas , Curcumina , Staphylococcus aureus Resistente à Meticilina , Infecção dos Ferimentos , Animais , Camundongos , Hidrogéis , Antibacterianos , Peptídeos , Cicatrização , Concentração de Íons de Hidrogênio
20.
BMC Microbiol ; 24(1): 127, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627609

RESUMO

BACKGROUND: In Ethiopia, milk production and handling practices often lack proper hygiene measures, leading to the potential contamination of milk and milk products with Staphylococcus aureus (S. aureus), including methicillin-resistant strains, posing significant public health concerns. This study aimed to investigate the occurrence, antimicrobial susceptibility profiles and presence of resistance genes in S. aureus strains isolated from milk and milk products. METHODS: A cross-sectional study was conducted in the Arsi highlands, Oromia, Ethiopia from March 2022 to February 2023. A total of 503 milk and milk product samples were collected, comprising 259 raw milk, 219 cottage cheese, and 25 traditional yogurt samples. S. aureus isolation and coagulase-positive staphylococci enumeration were performed using Baird-Parker agar supplemented with tellurite and egg yolk. S. aureus was further characterized based on colony morphology, Gram stain, mannitol fermentation, catalase test, and coagulase test. Phenotypic antimicrobial resistance was assessed using the Kirby-Bauer disc diffusion method, while the polymerase chain reaction (PCR) was employed for confirming the presence of S. aureus and detecting antimicrobial resistance genes. RESULTS: S. aureus was detected in 24.9% of the milk and milk products, with the highest occurrence in raw milk (40.9%), followed by yogurt (20%), and cottage cheese (6.4%). The geometric mean for coagulase-positive staphylococci counts in raw milk, yogurt, and cottage cheese was 4.6, 3.8, and 3.2 log10 CFU/mL, respectively. Antimicrobial resistance analysis revealed high levels of resistance to ampicillin (89.7%) and penicillin G (87.2%), with 71.8% of the isolates demonstrating multidrug resistance. Of the 16 S. aureus isolates analyzed using PCR, all were found to carry the nuc gene, with the mecA and blaZ genes detected in 50% of these isolates each. CONCLUSION: This study revealed the widespread distribution of S. aureus in milk and milk products in the Arsi highlands of Ethiopia. The isolates displayed high resistance to ampicillin and penicillin, with a concerning level of multidrug resistance. The detection of the mecA and blaZ genes in selected isolates is of particular concern, highlighting a potential public health hazard and posing a challenge to effective antimicrobial treatment. These findings highlight the urgent need to enhance hygiene standards in milk and milk product handling and promote the rational use of antimicrobial drugs. Provision of adequate training for all individuals involved in the dairy sector can help minimize contamination. These measures are crucial in addressing the threats posed by S. aureus, including methicillin-resistant strains, and ensuring the safety of milk and its products for consumers.


Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Animais , Staphylococcus aureus , Leite , Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/genética , Coagulase/genética , Etiópia , Estudos Transversais , Infecções Estafilocócicas/epidemiologia , Staphylococcus , Anti-Infecciosos/farmacologia , Ampicilina/farmacologia , Testes de Sensibilidade Microbiana
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