Methicillin-resistant S. Aureus Strains Research Articles

Synergistic potential of Leu10-teixobactin and cefepime against multidrug-resistant Staphylococcus aureus

Staphylococcus aureus (S. aureus) is a significant Gram-positive opportunistic pathogen behind many debilitating infections. β-lactam antibiotics are conventionally prescribed for treating S. aureus infections. However, the adaptability of S. aureus in evolving resistance to multiple β-lactams contributed to the persistence and spread of infections, exemplified in the emergence of methicillin-resistant S. aureus (MRSA). In the present study, we investigated the efficacies of the synthetic teixobactin analogue, Leu10-teixobactin, combined with the penicillinase-resistant cephalosporin cefepime against MRSA strains. The Leu10-teixobactin and cefepime combination exerted synergism against most strains tested in broth microdilution assay. Time-kill profiles showed that both Leu10-teixobactin and cefepime predominantly exhibited synergistic activity, with > 2.0-log10CFU decrease compared to monotherapy at 24 h. Moreover, biofilm assays revealed a significant inhibition of biofilm production in ATCC™43300 cells treated with sub-MICs of Leu10-teixobactin and cefepime. Subsequent electron microscopy studies showed more extensive damage with the combination therapy compared to monotherapies, including aberrant bacterial morphology, vesicle formation and substantial lysis, indicating combined damage to the cell wall. Quantitative real-time PCR revealed marked perturbation of genes mecA, sarA, atlA, and icaA, substantiating the apparent mode of combined antibacterial action of both antibiotics against peptidoglycan synthesis and initial biofilm production. Hence, the study highlights the prospective utility of the Leu10-teixobactin-cefepime combination in treating MRSA infections via β-lactam potentiation.

Prevalence, antimicrobial resistance, virulence gene distribution and SCCmec typing of methicillin-resistant Staphylococcus aureus isolated from raw milk and dairy products.

Researchers have focused on Staphylococcus aureus because it is transmitted through food, such as milk and dairy products, and causes human diseases. Prevalence, antimicrobial resistance, presence, and distribution of methicillin-resistant S. aureus (MRSA) virulence genes isolated from raw milk and dairy products were evaluated. 300 samples of dairy products were collected from Shahrekord, Iran. S. aureus was identified using biochemical tests and screened for sensitivity to 13 antibiotics to identify resistance genes. In addition, SCCmec typing was performed. Out of 300, S. aureus was found in 82 samples. Raw milk had the highest contamination with S. aureus (60 of 82), followed by cheese (15 of 82), and butter (7 of 82). At least one resistance gene was present in every isolate of S. aureus. Virulence factors and enterotoxin-coding genes, such as sea, seb, sec, and sed were highly distributed. The results of this study revealed the presence of toxin-producing MRSA strains in raw milk and dairy products. MRSA in dairy farms is an important risk factor for the spread of staphylococcal infections; therefore, further studies are needed to find strategies for controlling the presence of S. aureus, especially MRSA, in dairy products.

Marine Bacillus pumilus substances exhibit antimicrobial effect on multidrug-resistant Staphylococcus aureus.

This study aimed to assess the antimicrobial potential of Bp1-AdE, produced by Bacillus pumilus 64-1, and to investigate its mode of action against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). Bp-1AdE, derived from sponge-associated B. pumilus, exhibited bactericidal activity at 1,550 µg ml-1 against S. aureus ATCC29213 and MRSA strains. Light and fluorescence microscopy revealed drastic cell lysis of S. aureus treated with Bp-1AdE. Scanning and transmission electron microscopy suggested that Bp-1AdE disrupts the cytoplasmic membrane. Toxicity assays showed that Bp-1AdE was non-toxic to Tenebrio molitor larvae. Liquid chromatography-mass spectrometry (LC-MS) and Global Natural Product Social (GNPS) spectral libraries identified four substances within Bp-1AdE, including aliphatic alcohols [3,4-dipentylhexane-2,5-diol and 1,1'-(4,5-dibutyl-3,6-dimethylcyclohexane-1,2-diyl)bis(ethan-1-one)] and terpenoids (cholic acid and canrenone). Bp-1AdE demonstrated selective toxicity and bactericidal activity, highlighting its potential for controlling infections caused by multidrug-resistant S. aureus strains.

Modulatory effects of sub-MIC concentrations silver nanoparticles on virulence factor gene expression in Staphylococcus aureus

BackgroundSilver nanoparticles (AgNPs) exhibit a dose-dependent anti-bacterial effect, and it was aimed in this study to investigate the impact of sub-minimum inhibitory concentration (MIC) doses of AgNPs on the expression of virulence genes in Staphylococcus aureus (S. aureus). MethodsMinimum inhibitory concentration (MIC) values for AgNPs were determined for 183 S. aureus isolates. Gene expression was assessed in 14 isolates with sea and seb genes treated with AgNPs at a sub-MIC dose of 1 μg/ml. Accordingly, these strains were exposed to 1 μg/ml doses of AgNPs, and gene expression levels of sea, seb, and agr were assessed using quantitative RT-PCR after 4- and 12-hour post-AgNPs inoculation at 37 °C. The impact of AgNPs on the virulence factors of S. aureus was investigated over different time points, focusing on methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates. ResultsAnalysis revealed significant reductions in gene expression levels of seb and agr after 4 h post-AgNPs treatment in the MSSA group (p < 0.05), with further decreases observed at 12 h for sea, seb, and agr genes (p < 0.0001). MRSA isolates exhibited significant declines in sea and agr gene expression levels at both time points (p < 0.0001). However, no significant changes were observed in seb gene expression among MRSA isolates. Fold-change analysis indicated time-dependent effects of AgNP treatment on gene expression, highlighting substantial alterations in gene expression levels over time, particularly in seb and agr genes. ConclusionThese results show that sub-MIC levels of AgNPs greatly decrease the gene expression of important virulence factors in MSSA and MRSA strains, indicating their promise as treatments for S. aureus infections, particularly at 12 h post-treatment. The differential response between MSSA and MRSA isolates highlights the importance of strain variation in antimicrobial strategies.

Analysis of genetic signatures of virulence and resistance in foodborne Staphylococcus aureus isolates from Algeria

Staphylococcus aureus, a frequent commensal of the human microbiota, also frequently associated with various infections. This study aimed to genetically characterize foodborne methicillin resistant S. aureus (MRSA) in Oran, Algeria. From a total of 474 food matrices, 30 MRSA strains were isolated and characterized using whole genome sequencing (WGS) and bioinformatics. The genomes were assessed for antimicrobial resistance and virulence genes, sequence and spa types and single nucleotide polymorphism (SNP) to establish their relationship. The prevalence of S. aureus was 34.38% with MRSA accounting for 18.40%. MRSA strains showed high resistance to penicillinG, ampicillin and tetracycline. However, inconsistencies were noted between phenotypic and genotypic resistance for methicillin, aminoglycosides, and phenicolates, with mecA gene identified in three isolates. The isolates revealed eight different sequence types (predominantly ST97 and ST45) and eleven spa types (mainly t230 and t8503), correlating with SNP clusters except for isolates belonging to ST7200.86.66% of isolates harboured at least one enterotoxin gene underscores their potential public health threat. This investigation highlights the genetic heterogeneity among S. aureus regarding virulence and antimicrobial resistance, shedding light into food safety in Algeria and the ease of using WGS approach to rapidly characterize bacterial pathogens in community environments.

Detection of Indicator Genes in Methicillin-Resistant Staphylococcus Aureus (MRSA) Isolated from Meat Samples

Aims: The presence of Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), on retail meat products is becoming more and more of a concern. The aim of the present study is to examine the recovered strains of methicillin-resistant Staphylococcus aureus (MRSA) from different retail beef in Najaf/ Iraq. Methodology and results: The phenotypically by conventional identification. Genotypical examination was made also by polymerase chain reaction (PCR) to detect the genes some diagnostic genes for the enterotoxins sea, seb, sed. More than 200 strains of Staphylococcus aureus, from different butchers meat shops. MRSA strains were characterized by streaking on different selective media and biochemically identified as Staphylococcus aureus MRSA. The results showed that the appearance of sea genes in 51% of the isolates. Seb gene was in 18.90% of the isolates while 5.40 % of the isolates displayed sed gene. Also, Resistance towards six different antimicrobial agents was assessed and revealed that the tested strains of Staphylococcus aureus showed different level of resistance for Streptomycin 100%, Cotrimoxazole 100% , Cephalothin 45.90%and Tetracycline 32.3%. Conclusion, significance and impact of study: the majority of molecular isolate types have been connected to human infections globally, demonstrating that these S. aureus strains in Iraq have a potential for serious pathogenicity. The presence of the genes (sea, sed, and seb) in the MERSA isolates from meat in this study is alarming and raising public health concerns.

Improved N-phenylpyrrolamide inhibitors of DNA gyrase as antibacterial agents for high-priority bacterial strains

In this work, we describe an improved series of N-phenylpyrrolamide inhibitors that exhibit potent activity against DNA gyrase and are highly effective against high-priority gram-positive bacteria. The most potent compounds show low nanomolar IC50 values against Escherichia coli DNA gyrase, and in addition, compound 7c also inhibits E. coli topoisomerase IV in the nanomolar concentration range, making it a promising candidate for the development of potent dual inhibitors for these enzymes. All tested compounds show high selectivity towards the human isoform DNA topoisomerase IIα. Compounds 6a, 6d, 6e and 6f show MIC values between 0.031 and 0.0625 μg/mL against vancomycin-intermediate S. aureus (VISA) and Enterococcus faecalis strains. Compound 6g shows an inhibitory effect against the methicillin-resistant S. aureus strain (MRSA) with a MIC of 0.0625 μg/mL and against the E. faecalis strain with a MIC of 0.125 μg/mL. In a time-kill assay, compound 6d showed a dose-dependent bactericidal effect on the MRSA strain and achieved bactericidal activity at 8 × MIC after 8 h. The duration of the post-antibiotic effect (PAE) on the MRSA strain for compound 6d was 2 h, which corresponds to the PAE duration for ciprofloxacin. The compounds were not cytotoxic at effective concentrations, as determined in an MTS assay on the MCF-7 breast cancer cell line.

Genomic Characterization of Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Implicated in Bloodstream Infections, KwaZulu-Natal, South Africa: A Pilot Study.

Staphylococcus aureus is an opportunistic pathogen and a leading cause of bloodstream infections, with its capacity to acquire antibiotic resistance genes posing significant treatment challenges. This pilot study characterizes the genomic profiles of S. aureus isolates from patients with bloodstream infections in KwaZulu-Natal, South Africa, to gain insights into their resistance mechanisms, virulence factors, and clonal and phylogenetic relationships. Six multidrug-resistant (MDR) S. aureus isolates, comprising three methicillin-resistant S. aureus (MRSA) and three methicillin-susceptible S. aureus (MSSA), underwent whole genome sequencing and bioinformatics analysis. These isolates carried a range of resistance genes, including blaZ, aac(6')-aph(2″), ant(9)-Ia, ant(6)-Ia, and fosB. The mecA gene, which confers methicillin resistance, was detected only in MRSA strains. The isolates exhibited six distinct spa types (t9475, t355, t045, t1265, t1257, and t7888) and varied in virulence gene profiles. Panton-Valentine leukocidin (Luk-PV) was found in one MSSA isolate. Two SCCmec types, IVd(2B) and I(1B), were identified, and the isolates were classified into four multilocus sequence types (MLSTs), with ST5 (n = 3) being the most common. These sequence types clustered into two clonal complexes, CC5 and CC8. Notably, two MRSA clones were identified: ST5-CC5-t045-SCCmec_I(1B) and the human-associated endemic clone ST612-CC8-t1257-SCCmec_IVd(2B). Phylogenomic analysis revealed clustering by MLST, indicating strong genetic relationships within clonal complexes. These findings highlight the value of genomic surveillance in guiding targeted interventions to reduce treatment failures and mortality.

Unmasking a looming crisis: Escalating MIC of last resort drugs against MRSA isolates from a tertiary care hospital in Central India

PurposeThe Centers for Disease Control and Prevention has classified methicillin-resistant S aureus (MRSA) as a serious public health threat. The escalating minimum inhibitory concentration (MIC) of standard anti-methicillin-resistant S aureus (MRSA) drugs within the susceptible range, known as "MIC creep," jeopardizes their effectiveness against MRSA infections, posing additional challenges in managing MRSA infections. This cross-sectional study was conducted in a tertiary care hospital in Central India to assess the susceptibility trends of clinical MRSA isolates against commonly used anti-MRSA drugs and to observe MIC creep, if any, over three years (2020–2022). MethodsThe study included 158 non-repetitive clinical MRSA isolates. The MICs of vancomycin, teicoplanin, and linezolid were determined in MRSA strains using agar dilution, while the MIC of daptomycin was performed by broth microdilution. MIC creep was assessed by calculating MIC50, MIC90, Modal MIC, G-mean MIC, and susceptible and resistant percentages for the fiscal years 2020, 2021, and 2022. ResultsOf the 158 MRSA isolates, none were resistant to vancomycin, teicoplanin, and daptomycin, but two showed resistance to linezolid (LRSA). However, fifteen isolates showed intermediate resistance to vancomycin (VISA), and five showed intermediate resistance to teicoplanin (TISA). MIC of these anti-MRSA drugs increased in 2021 and 2022 compared to 2020. G-mean MIC for vancomycin, teicoplanin, and linezolid in MRSA strains increased significantly over the study period, while daptomycin MIC remained relatively stable, with a slight increase in 2021 and 2022. There was a high resistance rate for clindamycin, doxycycline, and chloramphenicol among VISA, TISA, and LRSA isolates compared to MRSA. ConclusionsDuring the three years of the study, “MIC creep” was observed in vancomycin, teicoplanin, and linezolid and, to some extent, for daptomycin in MRSA strains. The recovery of VISA, TISA, and linezolid-resistant MRSAs is worrisome, suggesting possible MRSA treatment failure and being a forerunner of resistant strains.

Machine learning assisted identification of antibiotic-resistant Staphylococcus aureus strains using a paper-based ratiometric sensor array

Staphylococcus aureus, a versatile human pathogen, significantly impacts global health causing a broad spectrum of medical conditions that range from minor skin infections to life-threatening diseases. The clinical importance of S. aureus is underscored by its resistance to multiple antibiotics and formation of biofilms, providing protection against antimicrobials and immune responses. To date, the identification of antimicrobial-resistant (AMR) S. aureus strains, such as methicillin-resistant S. aureus (MRSA) and vancomycin-intermediate S. aureus (VISA), requires time-consuming and expensive methodologies, including culture-based, molecular, and phenotypic techniques. Previously, we developed a paper-based ratiometric sensor array composed of fluorescent sensor dyes (3-hydroxyflavone derivatives) pre-adsorbed on paper microzone plates. Combined with machine learning algorithms such as neural networks, this sensor effectively discriminated 16 bacterial species and determined their Gram status. In this study, we evaluate its ability to distinguish antibiotic-resistant S. aureus strains and their biofilms. Our results demonstrate that the sensor array, in conjunction with LDA and neural networks, successfully differentiated three common laboratory MRSA strains from three methicillin-susceptible S. aureus (MSSA) strains with 82.5% accuracy. Furthermore, using support vector machines, this sensor was able to distinguish and categorically classify MRSA, MSSA, and VISA clinical isolates with 97.5% accuracy. Remarkably, beyond distinguishing planktonic cultures, this sensor array demonstrated a formidable capability to discriminate AMR S. aureus biofilms, achieving over 80% accuracy. Combined, the results of this study highlight the paper-based sensor array’s significant potential as a robust diagnostic tool to accurately, rapidly, and easily identify drug-resistant S. aureus strains in clinically relevant settings.

Capturing MRSA Diversity by Integrating Genomic and Epidemiological Data of Patients and their Spaces

Background: Methicillin-resistant S. aureus (MRSA) is known to cause frequent and severe infections in community living centers, potentially resulting in significant mortality for elderly patients. More research is needed to understand how to utilize genomic and epidemiological data to understand characteristics that may lead to increased transmission. We hypothesized that combining genomic and epidemiological information to sample patients and their environments during long-term stays, we will be able to capture a diverse set of MRSA strains. Method: This work included genome sequencing of patient and environmental samples from 11 patients within the VA Ann Arbor Healthcare System from May 4, 2021- November 16, 2022. All 11 patients tested positive for MRSA during their stay (mean days = 31). Patient and environmental samples were taken throughout their stays, screened for MRSA, and whole-genome sequenced. Single nucleotide variants (SNVs) were identified by mapping reads and calling variants against strain-specific reference genomes. We used ape v5.6-2 in R v4.2.2 to analyze and infer evolution, acquisition, and transmission events based on pairwise SNV distances. Genomic clusters were determined using stats v3.6.2, with a SNV distance threshold of 20. Result: Samples that were collected from patient bodily sites were able to reveal 20 distinct genomic clusters of MRSA (patient hands: n = 10, nares: n = 7, groin: n = 3). Environmental samples from patient environments also revealed distinct genomic MRSA clusters (tv remote: n = 9, toilet seat and bed rail: n = 6, table top, bed control, and call button: n = 5, bed curtain: n = 4, pulse ox = 2, cell phone, tray, pulse ox, mat, body hoist wrap, and bed: n = 1). Conclusion: The identification of various genomic clusters from patients and their environmental reservoirs suggests intrahost variation that can only be captured by using a more holistic approach of integrating epidemiology and genomic sequencing. Developing studies that incorporate genomic data, various environmental sources, and multiple isolates over time within community living centers can increase our understanding of strains that are more likely to transmit, survive on living and non-living surfaces and therefore lead to improved recommendation for infection prevention interventions and drivers of endemicity.Disclosure: Lona Mody: NIH, VA, CDC, Kahn Foundation; Honoraria: UpToDate; Contracted Research: Nano-Vibronix

Effect of gallium nitrate on the antibacterial activity of vancomycin in methicillin-sensitive and resistant Staphylococcus aureus.

The extension of multidrug-resistant strains of Staphylococcus aureus (S. aureus) is one of the main health challenges in the world, which requires serious solutions to deal with it. Combination therapies using conventional antibiotics and new antibacterial compounds that target different bacterial pathways are effective methods against resistant bacterial infections. Gallium is an iron-like metal that competes with iron for uptake into bacteria and has the potential to disrupt iron-dependent vital processes in bacteria. In this study, we explored the antibacterial effects of gallium nitrate (Ga(NO3)3) and vancomycin alone and in combination with each other on methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) using microdilution assay and checkerboard test, respectively. Then, their effect on the formation and destruction of biofilms was investigated. Finally, the amount of ROS production in the presence of these two compounds in bacteria was evaluated. The results indicated that the vancomycin/ Ga(NO3)3 combination reduced the MIC of vancomycin in the MRSA strain and had an additive effect on it. Vancomycin plus Ga(NO3)3 reduced the formation of biofilms and increased the destruction of biofilms formed in both strains, especially in the MRSA strain. ROS production was also higher in the combination of vancomycin with Ga(NO3)3 compared to vancomycin alone, especially in MRSA. Therefore, our results showed that Ga(NO3)3 enhances the antibacterial activity of vancomycin and this combination therapy can be considered as a new strategy for the treatment of MRSA infections.

Genomic characterization of Staphylococcus aureus isolated from patients admitted to intensive care units of a tertiary care hospital: epidemiological risk of nasal carriage of virulent clone during admission.

We conducted a molecular epidemiological study of Staphylococcus aureus using whole-genome sequence data and clinical data of isolates from nasal swabs of patients admitted to the intensive care unit (ICU) of Hiroshima University hospital. The relationship between isolate genotypes and virulence factors, particularly for isolates that caused infectious diseases during ICU admission was compared with those that did not. The nasal carriage rates of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) in patients admitted to the ICU were 7.0% and 20.1%, respectively. The carriage rate of community-acquired (CA)-MRSA was 2.3%, accounting for 32.8% of all MRSA isolates. Whole-genome sequencing analysis of the MRSA isolates indicated that most, including CA-MRSA and healthcare-associated (HA)-MRSA, belonged to clonal complex (CC) 8 [sequence type (ST) 8] and SCCmec type IV. Furthermore, results for three disease foci (pneumonia, skin and soft tissue infection, and deep abscess) and the assessment of virulence factor genes associated with disease conditions [bacteremia, acute respiratory distress syndrome (ARDS), disseminated intravascular coagulopathy (DIC), and septic shock] suggested that nasal colonization of S. aureus clones could represent a risk for patients within the ICU. Particularly, MRSA/J and MSSA/J may be more likely to cause deep abscess infection; ST764 may cause ventilation-associated pneumonia, hospital-acquired pneumonia and subsequent bacteremia, and ARDS, and tst-1-positive isolates may cause DIC onset.IMPORTANCENasal colonization of MRSA in patients admitted to the intensive care unit (ICU) may predict the development of MRSA infections. However, no bacteriological data are available to perform risk assessments for Staphylococcus aureus infection onset. In this single-center 2-year genomic surveillance study, we analyzed all S. aureus isolates from nasal swabs of patients admitted to the ICU and those from the blood or lesions of in-patients who developed infectious diseases in the ICU. Furthermore, we identified the virulent clones responsible for causing infectious diseases in the ICU. Herein, we report several virulent clones present in the nares that are predictive of invasive infections. This information may facilitate the design of preemptive strategies to identify and eradicate virulent MRSA strains, reducing nosocomial infections within the ICU.

Phenotypic and genotypic characterization of methicillin and vancomycin-resistant Staphylococcus aureus isolated from human clinical samples in Kerman hospitals, Iran

Today, methicillin-resistant S. aureus (MRSA) isolates are widely spread in both communities and hospitals, causing high morbidity and mortality worldwide. However, the emergence of vancomycin resistance among MRSA isolates has been perceived as a formidable threat to therapeutic management. Therefore, the present study aimed to determine the frequency and antibiotic susceptibility of MRSA and vancomycin-resistant S. aureus (VRSA) strains in Kerman hospitals in Iran. A total of 455 human clinical samples were collected from Kerman hospitals. The samples were examined for the presence of S. aureus and the isolates were tested for their susceptibility to antibiotics by disk diffusion method. MRSA and VRSA isolates were detected by a combination of phenotypic and genotypic methods. Sixty-five coagulase-positive S. aureus strains were isolated, and the higher isolation rate was from wound samples (47.7%) compared with blood (18.5%), respiratory tract secretions (10.8%), urine (10.8%), body fluids (9.2%), abscess (1.5%), and cerebrospinal fluids (1.5%). The isolates exhibited high resistance toward tetracycline (69.2%). Thirty-four isolates (52.3%) were categorized as MRSA (phenotypically resistant to cefoxitin). mecA gene was amplified in 97.1% of MRSA strains. Moreover, only one MRSA strain was resistant to vancomycin (MIC=128), and this isolate carried the vanA gene. The frequency of MRSA was not significantly associated with gender, age, sample type, and sampling locality (p&gt;0.05). Given the alarming rate of resistance among MRSA isolates, monitoring of antibiotic resistance should be performed to reduce treatment failure in patients with staphylococcal infections. Although vancomycin remains a drug of choice for MRSA, our study suggests that its efficacy may be limited by resistance development.

Strain Differences in Bloodstream and Skin Infection: Methicillin-Resistant Staphylococcus aureus Isolated in 2018-2021 in a Single Health System.

Staphylococcus aureus is a common cause of skin and soft-tissue infections (SSTIs) and has become the most common cause of bloodstream infections (BSIs) in recent years, but whether the strains causing these two clinical syndromes overlap has not been studied adequately. USA300/500 (clonal complex [CC] 8-sequence type [ST] 8) and USA100 (CC5-ST5) have dominated among methicillin-resistant S aureus (MRSA) strains in the United States since the early 2000s. We compared the genomes of unselected MRSA isolates from 131 SSTIs with those from 145 BSIs at a single US center in overlapping periods in 2018-2021. CC8 MRSA was more common among SSTIs, and CC5 was more common among BSIs, consistent with prior literature. Based on clustering genomes with a threshold of 15 single-nucleotide polymorphisms, we identified clusters limited to patients with SSTI and separate clusters exclusively comprising patients with BSIs. However, we also identified eight clusters that included at least one SSTI and one BSI isolate. This suggests that virulent MRSA strains are transmitted from person to person locally in the healthcare setting or the community and that single lineages are often capable of causing both SSTIs and BSIs.

Herbal Bioactive Compounds for Skin Infections and Inflammatory Conditions

Skin microbiota is an integral part of the human immune system. Staphylococcus aureus is one of the essential components of the normal flora. Approximately 20–30% of healthy individuals are persistently colonized with S. aureus, whereas the remainders are considered low-level intermittent carriers. Despite these natural aspects of existence, S. aureus can be a major opportunistic human pathogen. This versatile microorganism can infect a variety of anatomical sites, causing a broad spectrum of pathologies ranging from superficial to invasive infections. It developed a variety of strategies to adopt to a changing microenvironment. This attributed to the emergence of resistance to antibiotics of different classes during the past six decades. Methicillin-resistant S. aureus (MRSA) was originally confined to health-care settings (health-care-associated MRSA). Later on, community-acquired MRSA was identified as another source of infections. Recent figures indicate that MRSA strains have been associated with approximately 75% of all S. aureus infections worldwide. Several guidelines have been published to establish an adequate treatment of skin and soft tissue infections (SSTIs) caused by MRSA strains. In the first part of this review, we focus on current treatment guidelines with a focus on medical drug therapy, but drug therapy has its own limitations. Recently, the interest in herbal remedies has greatly increased. There is growing evidence of antimicrobial activity of medicinal plants and their extracts. The second part of this review is dedicated to herbal compounds to circumvent antibiotic resistance. Herbal compounds may potentiate the action of antibiotics and restore the activities of antibacterial agents against which S. aureus has developed a drug resistance. Part 2 focuses on the role of S. aureus in pathology of the two major inflammatory skin diseases, i.e., atopic dermatitis (AD) and psoriasis. Finally, Part 3 provides an overview on natural compounds with antimicrobial activity against S. aureus and possible use in the treatment of SSTIs,

Study of the sensitivity of methicillin-resistant &lt;i&gt;Staphylococcus aureus&lt;/i&gt; to antibiotics and bacteriophage preparations

Objective. To evaluate the sensitivity of methicillin-resistant Staphylococcus aureus strains to antibiotics and therapeutic and prophylactic preparations of bacteriophages. Materials and methods. The antibiotic sensitivity of strains of methicillin-resistant S.aureus was studied by the disco-diffusion method, the determination of the minimum inhibitory concentrations of vancomycin and linezolid by broth microdilution method, and ceftaroline by E-tests. The sensitivity of methicillin-resistant S.aureus to bacteriophage preparations was studied. Results. It has been established that linezolid and vancomycin are quite active drugs against methicillin-resistant S.aureus (MRSA), however, resistance to them begins to develop. MRSA resistance to fluoroquinolones and cefoxitin was the highest of all antibiotics tested; the results obtained with cefoxitin can be interpreted for other cephalosporins (except ceftaroline) and all penicillins. Only 67.9% of MRSA strains retained sensitivity to ceftaroline, but ceftaroline-resistant strains had low levels of minimal inhibitory concentration. The preparations of the bacteriophages “Sextaphage” and “Piobacteriophage Phagio” showed their lytic activity only in relation to 35.8% and 18.9% of MRSA isolates, respectively. Conclusion. Monitoring the development of antibiotic resistance in methicillin-resistant S.aureus is an important part of the strategy of rational antibiotic therapy for staphylococcal infections. Only taking into account the preliminary step-by-step determination of the phage sensitivity of the causative agent of the disease, bacteriophage preparations can be considered as a completely possible alternative to antibiotics for the treatment of purulent inflammatory diseases caused by MRSA.

Evaluation of the Effect of Lactobacillus acidophilus ATCC 4356 Bacteriocin against Staphylococcus aureus.

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. 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. 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.

Interaction of Selected Commercial Antiseptics with Natural Products against Methicillin-Resistant Staphylococcus aureus Strain

The carriage of methicillin-resistant S. aureus (MRSA) strains may determine the subsequent occurrence of infection, which mainly affects patients after surgeries. Therefore, its eradication with the use of antibiotics or antiseptics is a crucial method of preventing staphylococcal self-infections. The observed increase in bacterial resistance to known antibacterial substances poses a huge challenge to scientists. The aim of this study was to analyze the interaction of selected commercial antiseptics (Braunol, CITROclorex 2%, Microdacyn 60 Wound Care, Octenisept and Prontoderm Solution) with natural products (carvacrol, β-citronellol, geraniol, eugenol, farnesol, (-)-menthone, eucalyptol, limonene, linalyl acetate and trans-anethole) against the MRSA standard strain. The antistaphylococcal activity of commercial antiseptics in combination with natural products against MRSA was determined using the checkerboard method. The obtained results showed that most combinations decreased the MIC level of the commercial antiseptic and natural compounds. A statistically significant decrease in the MIC value of the antiseptic and natural constituent was observed for the Braunol–β-citronellol combination. Such a significant decrease in the MIC value of the natural compound against the analyzed strain was also detected for the Octenisept–β-citronellol and Prontoderm Solution–β-citronellol combinations. The interaction analysis showed that out of all 20 combinations of individual antiseptics with substances of natural origin, two combinations showed a synergistic effect (Braunol–β-citronellol, Braunol–carvacrol), and three combinations showed an additive effect (Braunol–eugenol, Braunol–geraniol, Prontoderm Solution–β-citronellol). The use of Braunol in combination with β-citronellol or carvacrol may become an alternative method of eradicating MRSA strains. However, further studies are needed to determine the toxicity of the analyzed combinations.

Antibiotic resistance, biofilm formation, and molecular epidemiology of Staphylococcus aureus in a tertiary hospital in Xiangyang, China.

Staphylococcus aureus is a common clinical pathogen that causes various human infections. The aim of this study was to investigate the antibiotic susceptibility pattern, molecular epidemiological characteristics, and biofilm formation ability of S. aureus isolates from clinical specimens in Xiangyang and to analyze the correlation among them. A total of 111 non-duplicate S. aureus isolates were collected from the Affiliated Hospital of Hubei University of Arts and Science. All isolates were tested for antibacterial susceptibility. Methicillin-resistant S. aureus (MRSA) was identified by the mecA gene PCR amplification. All isolates were analyzed to determine their biofilm-forming ability using the microplate method. The biofilm-related gene was determined using PCR. SCCmec, MLST, and spa types of MRSA strains were performed to ascertain the molecular characteristics. Among the 111 S. aureus isolates, 45 (40.5%) and 66 (59.5%) were MRSA and MSSA, respectively. The resistance of MRSA strains to the tested antibiotics was significantly stronger than that of MSSA strains. All isolates were able to produce biofilm with levels ranging from strong (28.9%, 18.2%), moderate (62.2%, 62.1%), to weak (8.9%, 19.7%). Strong biofilm formation was observed in MRSA strains than in MSSA strains, based on percentages. There were dynamic changes in molecular epidemic characteristics of MRSA isolates in Xiangyang. SCCmecIVa-ST22-t309, SCCmecIVa-ST59-t437, and SCCmecIVa-ST5-t2460 were currently the main epidemic clones in this region. SCCmecIVa-ST5-t2460 and SCCmecIVa/III-ST22-t309 have stronger antibiotic resistance than SCCmecIVa-ST59-t437 strains, with resistance to 6 ~ 8 detected non-β-lactam antibiotics. The molecular epidemic and resistance attributes of S. aureus should be timely monitored, and effective measures should be adopted to control the clinical infection and spread of the bacteria.