Staphylococcus aureus Infections and Human Intestinal Microbiota.

Staphylococcus aureus (S. aureus) is a common pathogen that can cause many human diseases, such as skin infection, food poisoning, endocarditis, and sepsis. These diseases can be minor infections or life-threatening, requiring complex medical management resulting in substantial healthcare costs. Meanwhile, as the critically ignored "organ," the intestinal microbiome greatly impacts physiological health, not only in gastrointestinal diseases but also in disorders beyond the gut. However, the correlation between S. aureus infection and intestinal microbial homeostasis is largely unknown. Here, we summarized the recent progress in understanding S. aureus infections and their interactions with the microbiome in the intestine. These summarizations will help us understand the mechanisms behind these infections and crosstalk and the challenges we are facing now, which could contribute to preventing S. aureus infections, effective treatment investigation, and vaccine development.

Clinical Efficacy of Nasal Screening and Methicillin-Resistant Staphylococcusaureus Decolonization in Total Hip Arthroplasty without Chlorhexidine Soap or Vancomycin.

Purpose: Nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) is a known risk factor for periprosthetic joint infection (PJI). In our facility, preoperative prophylaxis with mupirocin without the chlorhexidine soap scrub or vancomycin was consistently implemented for more than 15 years. This study aimed to evaluate the current screening and treatment of intranasal MRSA colonization in our elective primary THA patient population. Methods: All patients who underwent primary THA between April 2011, and March 2021 were included in this analysis. All patients were screened preoperatively for nasal MRSA approximately 1 month before surgery. Patients with nasal MRSA contamination are treated with topical mupirocin to eradicate the bacteria before surgery. The patients were examined again approximately two weeks before surgery. We evaluated the current screening and treatment of intranasal colonization with MRSA in our elective primary total hip arthroplasty (THA) patient population. Results: Out of 6251 patients, 106 (1.7%) had nasal MRSA contamination. The bacteria were not eradicated in three (3.6%) patients at the second screening. Twenty-two joints (0.35%) out of the 6251 had deep infections. Only 1 patient out of the 106 MRSA nasal carriers suffered from PJI. Twenty-one of the 6145 non-carriers had PJI. The difference between the prevalence of nasal MRSA contamination and the incidence of deep infections was not statistically significant. Conclusion: Our findings suggest that screening of all patients for nasal MRSA before THA followed by mupirocin calcium treatment if needed is sufficient PJI prophylaxis.

Genomic Insights into Staphylococcus aureus Isolates Exhibiting Diminished Daptomycin Susceptibility.

Daptomycin is one of the last therapeutic resources for multidrug-resistant gram-positive bacteria. Despite its structural similarities with glycopeptides, its mechanisms of action and resistance are different and in some respects are not completely understood. Mutations in several genes have been associated with daptomycin resistance, especially in mprF, walkR, rpoB and rpoC, but their role and importance remain to be elucidated. We have studied mutations in 11 genes, which have been previously associated with daptomycin non-susceptibility, in nine daptomycin-non-susceptible Staphylococcus aureus clinical isolates (daptomycin MIC: >1 mg/L). Susceptibility to daptomycin, vancomycin, linezolid, oxacillin, telavancin and dalbavancin was studied. walkR, agrA, cls1, cls2, fakA, pnpA, clpP, prs, rpoB, rpoC and mprF were amplified by PCR and sequenced. The sequences were compared with the S. aureus ATCC 25923 complete genome (GenBank gi: 685631213) by using BLAST® software. We did not find any changes in walkR, pnpA, prs and clpP. All isolates excepting isolate MSa5 showed a high number of significant mutations (between 13 and 25 amino acid changes) in mprF. Most isolates also showed mutations in the rpo genes, the cls genes and fakA. Daptomycin non-susceptibility in S. aureus clinical isolates seems to be reached through different mutation combinations when compared to S. aureus ATCC 25293. Especially mprF and cls1 showed very high polymorphism in most isolates. Meanwhile, one isolate, MSa5, showed only single mutation in mprF (P314T).

Mediterranean Plants with Antimicrobial Activity against Staphylococcus aureus, a Meta-Analysis for Green Veterinary Pharmacology Applications.

Antimicrobial resistance (AMR) has emerged as a global health crisis, necessitating the search for innovative strategies to combat infectious diseases. The unique biodiversity of Italian flora offers a treasure trove of plant species and their associated phytochemicals, which hold immense potential as a solution to address AMR. By investigating the antimicrobial properties of Italian flora and their phytochemical constituents, this study aims to shed light on the potential of phyto-complexes as a valuable resource for developing novel or supportive antimicrobial agents useful for animal production.

Genetic and Phenotypic Characterization of Subclinical Mastitis-Causing Multidrug-Resistant Staphylococcus aureus.

The core objective of this study was to genetically and phenotypically characterize subclinical mastitis-causing multidrug-resistant Staphylococcus aureus (MDRSA). In addition, risk factors associated with subclinical mastitis caused by MDRSA were investigated. Bacterial cultures were performed on 2120 mammary quarters, 40 swabs of milk utensils, 5 bulk tank milk samples, and 11 nostril and 11 hand swabs from milkers from five dairy farms. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was conducted for S. aureus identification. Antimicrobial resistance was screened phenotypically using the disk diffusion test in all S. aureus isolates. A biofilm formation assay; detection of genes associated with beta-lactam resistance, efflux pump, and biofilm formation; and pulsed-field gel electrophoresis (PFGE) were performed in all MDRSA isolates. Multi-locus sequence typing (MLST) was carried out in cefoxitin-resistant MDRSA isolates. A total of 188 S. aureus isolates from milk as well as two from milking utensils and one from bulk tank milk were identified. Most of the isolates (92.7%; 177 of 191) showed beta-lactam resistance, and 7% (14 of 191) were MDRSA. Interestingly, 36% (5 of 14) of MDRSA isolates were cefoxitin-resistant, but none carried mecA or mecC genes. Based on PFGE results, it was observed that S. aureus strains were more likely to be unique to a specific herd. Two clonal complexes were identified, CC97 (ST126; commonly livestock-associated) and CC1 (ST7440; usually community-associated). To the best of our knowledge, this is the first report of ST7440 isolated from bovine mastitis in Brazil. The risk factor results underscored the importance of considering parity, stage of lactation, SCC, milk production, and herd size when studying the risk of subclinical mastitis and antimicrobial resistance in S. aureus. Thus, to implement effective strategies to prevent subclinical mastitis in dairy herds and to minimize MDRSA spread, it is important to understand MDRSA strains' distribution and their antimicrobial resistance profile.

Whole Genome Sequencing and Molecular Epidemiology of Clinical Isolates of Staphylococcus aureus from Algeria.

Staphylococcus aureus is an important pathogen responsible for various healthcare- and community-acquired infections. In this study, whole genome sequencing (WGS) was used to genotype S. aureus clinical isolates from two hospitals in Algeria and to characterize their genetic determinants of antimicrobial resistance. Seventeen S. aureus isolates were included in this study. WGS, single-nucleotide polymorphism (SNP)-based phylogenetic analysis, in silico multilocus sequence typing (MLST), spa and staphylococcal cassette chromosome mec (SCCmec) typing and in silico antimicrobial resistance profiling were performed. Phenotypic antibiotic susceptibility testing was performed using the Vitek 2 system and the disk diffusion method. The isolates were separated into sequence types (STs), with ST80 being predominant; five clonal complexes (CCs); four spa types (t044, t127, t368, t386); and two SCCmec types (IVc and IVa). Whole genome analysis revealed the presence of the resistance genes mecA, blaZ, ermC, fusB, fusC, tetK, aph(3')-IIIa and aad(6) and mutations conferring resistance in the genes parC and fusA. The rate of multidrug resistance (MDR) was 64%. This work provides a high-resolution characterization of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) isolates and emphasizes the importance of continuous surveillance to monitor the spread of S. aureus in healthcare settings in the country.

Diflunisal and Analogue Pharmacophores Mediating Suppression of Virulence Phenotypes in Staphylococcus aureus.

Invasive methicillin-resistant Staphylococcus aureus (MRSA) infections are leading causes of morbidity and mortality that are complicated by increasing resistance to conventional antibiotics. Thus, minimizing virulence and enhancing antibiotic efficacy against MRSA is a public health imperative. We originally demonstrated that diflunisal (DIF; [2-hydroxy-5-(2,4-difluorophenyl) benzoic acid]) inhibits S. aureus virulence factor expression. To investigate pharmacophores that are active in this function, we evaluated a library of structural analogues for their efficacy to modulate virulence phenotypes in a panel of clinically relevant S. aureus isolates in vitro. Overall, the positions of the phenyl, hydroxyl, and carboxylic moieties and the presence or type of halogen (F vs. Cl) influenced the efficacy of compounds in suppressing hemolysis, proteolysis, and biofilm virulence phenotypes. Analogues lacking halogens inhibited proteolysis to an extent similar to DIF but were ineffective at reducing hemolysis or biofilm production. In contrast, most analogues lacking the hydroxyl or carboxylic acid groups did not suppress proteolysis but did mitigate hemolysis and biofilm production to an extent similar to DIF. Interestingly, chirality and the substitution of fluorine with chlorine resulted in a differential reduction in virulence phenotypes. Together, this pattern of data suggests virulence-suppressing pharmacophores of DIF and structural analogues integrate halogen, hydroxyl, and carboxylic acid moiety stereochemistry. The anti-virulence effects of DIF were achieved using concentrations that are safe in humans, do not impair platelet antimicrobial functions, do not affect S. aureus growth, and do not alter the efficacy of conventional antibiotics. These results offer proof of concept for using novel anti-virulence strategies as adjuvants to antibiotic therapy to address the challenge of MRSA infection.

Characterization of the Keratinolytic Activity of Three Streptomyces Strains and Impact of Their Co-Cultivation on This Activity.

In this study, we describe the characterization of three efficient chicken feather-degrading Streptomyces bacteria isolated from honeybee samples and assess the impact of their co-cultivation on this activity and antistaphylococcal activity. Streptomyces griseoaurantiacus AD2 was the strain showing the highest keratinolytic activity (4000 U × mL-1), followed by Streptomyces albidoflavus AN1 and Streptomyces drozdowiczii AD1, which both generated approximately 3000 U × mL-1. Moreover, a consortium constituted of these three strains was able to use chicken feathers as its sole nutrient source and growth in such conditions led to a significant increase in antibiotic production. S. griseoaurantiacus AD2 was the only strain that exhibited weak antimicrobial activity against Staphylococcus aureus. UPLC analyses revealed that a significant number of peaks detected in the extracts of co-cultures of the three strains were missing in the extracts of individual cultures. In addition, the production of specialized metabolites, such as undecylprodigiosin and manumycin A, was clearly enhanced in co-culture conditions, in agreement with the results of the antimicrobial bioassays against S. aureus. Our results revealed the benefits of co-cultivation of these bacterial species in terms of metabolic wealth and antibiotic production. Our work could thus contribute to the development of novel microbial-based strategies to valorize keratin waste.

6-Polyaminosteroid Squalamine Analogues Display Antibacterial Activity against Resistant Pathogens.

A series of 6-polyaminosteroid analogues of squalamine were synthesized with moderate to good yields and evaluated for their in vitro antimicrobial properties against both susceptible and resistant Gram-positive (vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus) and Gram-negative (carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa) bacterial strains. Minimum inhibitory concentrations against Gram-positive bacteria ranged from 4 to 16 µg/mL for the most effective compounds, 4k and 4n, and showed an additive or synergistic effect with vancomycin or oxacillin. On the other hand, the derivative 4f, which carries a spermine moiety like that of the natural trodusquemine molecule, was found to be the most active derivative against all the resistant Gram-negative bacteria tested, with an MIC value of 16 µg/mL. Our results suggest that 6-polyaminosteroid analogues of squalamine are interesting candidates for Gram-positive bacterial infection treatments, as well as potent adjuvants to fight Gram-negative bacterial resistance.

Clinical Impact of Staphylococcus aureus Skin and Soft Tissue Infections.

The pathogenic bacterium Staphylococcus aureus is the most common pathogen isolated in skin-and-soft-tissue infections (SSTIs) in the United States. Most S. aureus SSTIs are caused by the epidemic clone USA300 in the USA. These infections can be serious; in 2019, SSTIs with S. aureus were associated with an all-cause, age-standardized mortality rate of 0.5 globally. Clinical presentations of S. aureus SSTIs vary from superficial infections with local symptoms to monomicrobial necrotizing fasciitis, which can cause systemic manifestations and may lead to serious complications or death. In order to cause skin infections, S. aureus employs a host of virulence factors including cytolytic proteins, superantigenic factors, cell wall-anchored proteins, and molecules used for immune evasion. The immune response to S. aureus SSTIs involves initial responders such as keratinocytes and neutrophils, which are supported by dendritic cells and T-lymphocytes later during infection. Treatment for S. aureus SSTIs is usually oral therapy, with parenteral therapy reserved for severe presentations; it ranges from cephalosporins and penicillin agents such as oxacillin, which is generally used for methicillin-sensitive S. aureus (MSSA), to vancomycin for methicillin-resistant S. aureus (MRSA). Treatment challenges include adverse effects, risk for Clostridioides difficile infection, and potential for antibiotic resistance.

Non-Specific Signal Peptidase Processing of Extracellular Proteins in Staphylococcus aureus N315.

Staphylococcus aureus is one of the major community-acquired human pathogens, with growing multidrug-resistance, leading to a major threat of more prevalent infections to humans. A variety of virulence factors and toxic proteins are secreted during infection via the general secretory (Sec) pathway, which requires an N-terminal signal peptide to be cleaved from the N-terminus of the protein. This N-terminal signal peptide is recognized and processed by a type I signal peptidase (SPase). SPase-mediated signal peptide processing is the crucial step in the pathogenicity of S. aureus. In the present study, the SPase-mediated N-terminal protein processing and their cleavage specificity were evaluated using a combination of N-terminal amidination bottom-up and top-down proteomics-based mass spectrometry approaches. Secretory proteins were found to be cleaved by SPase, specifically and non-specifically, on both sides of the normal SPase cleavage site. The non-specific cleavages occur at the relatively smaller residues that are present next to the -1, +1, and +2 locations from the original SPase cleavage site to a lesser extent. Additional random cleavages at the middle and near the C-terminus of some protein sequences were also observed. This additional processing could be a part of some stress conditions and unknown signal peptidase mechanisms.

Rates and Predictors of Treatment Failure in Staphylococcus aureus Prosthetic Joint Infections According to Different Management Strategies: A Multinational Cohort Study-The ARTHR-IS Study Group.

INTRODUCTION: Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome. METHODS: A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016. The outcome variable was TF, including related mortality, clinical failure and functional loss both after the initial surgical procedure and after all procedures at 18 months. Predictors of TF were identified by logistic regression. Landmark analysis was used to avoid immortal time bias with rifampicin when debridement, antibiotics and implant retention (DAIR) was performed. RESULTS: One hundred twenty cases of SA-PJI were included. TF rates after the first and all surgical procedures performed were 32.8% and 24.2%, respectively. After all procedures, functional loss was 6.0% for DAIR and 17.2% for prosthesis removal. Variables independently associated with TF for the first procedure were Charlson ≥ 2, haemoglobin < 10 g/dL, bacteraemia, polymicrobial infection and additional debridement(s). For DAIR, TF was also associated with a body mass index (BMI) > 30 kg/m2 and delay of DAIR, while rifampicin use was protective. For all procedures, the variables associated with TF were haemoglobin < 10 g/dL, hip fracture and additional joint surgery not related to persistent infection. CONCLUSIONS: TF remains common in SA-PJI. Functional loss accounted for a substantial proportion of treatment failures, particularly after prosthesis removal. Use of rifampicin after DAIR was associated with a protective effect. Among the risk factors identified, anaemia and obesity have not frequently been reported in previous studies. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov, registration no. NCT03826108.

Staphylococcus aureus is one of the most virulent bacteria and frequently causes prosthetic joint infections.Knowledge of the treatment of this type of infection has advanced in recent years, and treatment guidelines have led to improved management. Typically, the successful treatment of these infections has been determined by clinical cure, that is, the symptoms of infection have disappeared, but has not taken into account loss of function (such as significant difficulties walking), which is critical for the patient's quality of life. Our aim in this study was to evaluate the success of current management strategies for S. aureus prosthetic joint infection, including recovery of functionality, and the factors that predict why some of these infections are not cured, to identify areas for improvement.In a multinational cohort of 128 patients with S. aureus prosthetic joint infection, rates of treatment failure were found to be high, with significant rates of loss of function, especially when the prosthesis needed to be removed. Loss of function was less frequent when the infection was initially treated with surgical cleaning without removal of the prosthesis, even when this procedure failed at first. We found that anaemia and obesity were associated with lower treatment success, and that the probability of treatment success increased when surgical cleaning without prosthesis removal was performed early, and when the antibiotic rifampicin was used in combination with another antibiotic.

Proline Transport and Growth Changes in Proline Transport Mutants of Staphylococcus aureus.

Staphylococcus aureus is a major cause of skin/soft tissue infections and more serious infections in humans. The species usually requires the importation of proline to be able to survive. Previous work has shown that single mutations in genes that encode for proline transporters affect the ability of S. aureus to survive in vitro and in vivo. To better understand proline transport in S. aureus, double and triple gene mutant strains were created that targeted the opuD, proP, and putP genes. Single gene mutants had some effect on proline transport, whereas double mutants exhibited significantly lower proline transport. An opuD prop putP triple gene mutant displayed the lowest proline transport under low- and high-affinity conditions. To assess growth differences caused by the mutations, the same mutants were grown in brain heart infusion (BHI) broth and defined staphylococcal medium (DSM) with various concentrations of proline. The triple mutant did not grow in DSM with a low concentration of proline and grew poorly in both DSM with a high proline concentration and BHI broth. These results show that S. aureus has multiple mechanisms to import proline into the cell and knocking out three of the main proline transporters significantly hinders S. aureus growth.

Hydroquinones Inhibit Biofilm Formation and Virulence Factor Production in Staphylococcus aureus.

Staphylococcus aureus is one of the major pathogens responsible for antimicrobial resistance-associated death. S. aureus can secrete various exotoxins, and staphylococcal biofilms play critical roles in antibiotic tolerance and the persistence of chronic infections. Here, we investigated the inhibitory effects of 18 hydroquinones on biofilm formation and virulence factor production by S. aureus. It was found that 2,5-bis(1,1,3,3-tetramethylbutyl) hydroquinone (TBHQ) at 1 µg/mL efficiently inhibits biofilm formation by two methicillin-sensitive and two methicillin-resistant S. aureus strains with MICs of 5 µg/mL, whereas the backbone compound hydroquinone did not (MIC > 400 µg/mL). In addition, 2,3-dimethylhydroquinone and tert-butylhydroquinone at 50 µg/mL also exhibited antibiofilm activity. TBHQ at 1 µg/mL significantly decreased the hemolytic effect and lipase production by S. aureus, and at 5−50 µg/mL was non-toxic to the nematode Caenorhabditis elegans and did not adversely affect Brassica rapa seed germination or growth. Transcriptional analyses showed that TBHQ suppressed the expression of RNAIII (effector of quorum sensing). These results suggest that hydroquinones, particularly TBHQ, are potentially useful for inhibiting S. aureus biofilm formation and virulence.

Unreliability of Clinical Prediction Rules to Exclude without Echocardiography Infective Endocarditis in Staphylococcus aureus Bacteremia.

BACKGROUND: It is unclear whether the use of clinical prediction rules is sufficient to rule out infective endocarditis (IE) in patients with Staphylococcus aureus bacteremia (SAB) without an echocardiogram evaluation, either transthoracic (TTE) and/or transesophageal (TEE). Our primary purpose was to test the usefulness of PREDICT, POSITIVE, and VIRSTA scores to rule out IE without echocardiography. Our secondary purpose was to evaluate whether not performing an echocardiogram evaluation is associated with higher mortality. METHODS: We conducted a unicentric retrospective cohort including all patients with a first SAB episode from January 2015 to December 2020. IE was defined according to modified Duke criteria. We predefined threshold cutoff points to consider that IE was ruled out by means of the mentioned scores. To assess 30-day mortality, we used a multivariable regression model considering performing an echocardiogram as covariate. RESULTS: Out of 404 patients, IE was diagnosed in 50 (12.4%). Prevalence of IE within patients with negative PREDICT, POSITIVE, and VIRSTA scores was: 3.6% (95% CI 0.1-6.9%), 4.9% (95% CI 2.2-7.7%), and 2.2% (95% CI 0.2-4.3%), respectively. Patients with negative VIRSTA and negative TTE had an IE prevalence of 0.9% (95% CI 0-2.8%). Performing an echocardiogram was independently associated with lower 30-day mortality (OR 0.24 95% CI 0.10-0.54, p = 0.001). CONCLUSION: PREDICT and POSITIVE scores were not sufficient to rule out IE without TEE. In patients with negative VIRSTA score, it was doubtful if IE could be discarded with a negative TTE. Not performing an echocardiogram was associated with worse outcomes, which might be related to presence of occult IE. Further studies are needed to assess the usefulness of clinical prediction rules in avoiding echocardiographic evaluation in SAB patients.

Staphylococcal Scalded Skin Syndrome in Neonates: Case Series and Overview of Outbreaks.

Skin and soft tissue infections caused by Staphylococcus aureus (S. aureus) cover a wide spectrum of diseases in neonates, including staphylococcal scalded skin syndrome (SSSS). We describe a representative case of SSSS in neonatal twins, which despite recurrence showed a mild clinical disease course. This case was part of a small outbreak on a neonatal intensive care unit and therefore exemplifies the existence of neonatal outbreaks with skin and soft tissue infections by S. aureus. Diagnosis is generally based on the clinical picture and response to antibiotics, but can be aided by histology and cultures. Sequence-based molecular techniques are available to evaluate typing and virulence of S. aureus in outbreak or surveillance settings. The pillars of treatment are antibiotics and supportive care. Methicillin resistance remains a topic of concern, especially in outbreak settings. Our overview of numerous outbreaks of neonatal S. aureus skin infections underlines the importance of outbreak management strategies, including screening to identify the source of the outbreak, and limiting exposure through hygienic measures and establishment of physical boundaries.

Investigation of methicillin-resistant Staphylococcus aureus, methicillin-susceptible Staphylococcus aureus, and Staphylococcus argenteus from wild long-tailed macaques (Macaca fascicularis) at Kosumpee Forest Park, Maha Sarakham, Thailand.

Background and Aim: In the past, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infections in both humans and animals has increased across Thailand. Staphylococcus argenteus has been associated with infections among humans, exotic pets, and livestock. Both species have been identified in non-human primate species from geographically diverse locations but not from non-human primates in Thailand. This study aimed to determine the presence of MRSA/methicillin-susceptible S. aureus (MSSA) and S. argenteus isolates collected from buccal swab samples in Macaca fascicularis at Kosumpee Forest Park (KFP), Maha Sarakham, Northeast Thailand. Materials and Methods: Aseptic buccal swab samples were collected from 30 free-ranging macaques in November 2018. All isolates were tested using multiple biochemical tests and S. aureus latex slide agglutination test. Presumptive S. aureus isolates were tested for the presence of the mecA gene using polymerase chain reaction (PCR) assays. The isolates were phenotypically determined to be resistant to a ß-lactam antibiotic using the disk diffusion method with a 30 mg cefoxitin disk. The isolates were analyzed by PCR for the non-ribosomal peptide synthetase (NRPS) gene to distinguish S. argenteus from S. aureus. Results: Fifteen macaques (50%) were colonized with S. aureus and 21 isolates were characterized. Three of the macaques carried both the MRSA and MSSA isolate. One animal carried both MRSA and S. argenteus isolate, and one animal carried only S. argenteus. The NRPS gene analysis confirmed that 2 isolates (9.52%) were S. argenteus and 19 isolates (90.48%) were S. aureus [five MSSA and 14 MRSA]. Conclusion: This study is the first to identify MRSA/MSSA and S. argenteus in wild free-ranging M. fascicularis from Thailand at the KFP in Maha Sarakham. This study is also the first report on the occurrence of S. argenteus carriage in M. fascicularis from Thailand.

Selection of Promising Novel Fragment Sized S. aureus SrtA Noncovalent Inhibitors Based on QSAR and Docking Modeling Studies.

Sortase A (SrtA) of Staphylococcus aureus has been identified as a promising target to a new type of antivirulent drugs, and therefore, the design of lead molecules with a low nanomolar range of activity and suitable drug-like properties is important. In this work, we aimed at identifying new fragment-sized starting points to design new noncovalent S. aureus SrtA inhibitors by making use of the dedicated molecular motif, 5-arylpyrrolidine-2-carboxylate, which has been previously shown to be significant for covalent binding SrtA inhibitors. To this end, an in silico approach combining QSAR and molecular docking studies was used. The known SrtA inhibitors from the ChEMBL database with diverse scaffolds were first employed to derive descriptors and interpret their significance and correlation to activity. Then, the classification and regression QSAR models were built, which were used for rough ranking of the virtual library of the synthetically feasible compounds containing the dedicated motif. Additionally, the virtual library compounds were docked into the "activated" model of SrtA (PDB:2KID). The consensus ranking of the virtual library resulted in the most promising structures, which will be subject to further synthesis and experimental testing in order to establish new fragment-like molecules for further development into antivirulent drugs.

Pleiotropic Effects of Statins: New Therapeutic Approaches to Chronic, Recurrent Infection by Staphylococcus aureus.

An emergent approach to bacterial infection is the use of host rather than bacterial-directed strategies. This approach has the potential to improve efficacy in especially challenging infection settings, including chronic, recurrent infection due to intracellular pathogens. For nearly two decades, the pleiotropic effects of statin drugs have been examined for therapeutic usefulness beyond the treatment of hypercholesterolemia. Interest originated after retrospective studies reported decreases in the risk of death due to bacteremia or sepsis for those on a statin regimen. Although subsequent clinical trials have yielded mixed results and earlier findings have been questioned for biased study design, in vitro and in vivo studies have provided clear evidence of protective mechanisms that include immunomodulatory effects and the inhibition of host cell invasion. Ultimately, the benefits of statins in an infection setting appear to require attention to the underlying host response and to the timing of the dosage. From this examination of statin efficacy, additional novel host-directed strategies may produce adjunctive therapeutic approaches for the treatment of infection where traditional antimicrobial therapy continues to yield poor outcomes. This review focuses on the opportunistic pathogen, Staphylococcus aureus, as a proof of principle in examining the promise and limitations of statins in recalcitrant infection.

Abscesos de córnea bilaterales en una paciente con SIDA. Presentación de un caso y revisión de la literatura / Corneal Abscess in a patient with aids: case report and literature review

El epitelio corneal es una importante barrera de defensa que impide el ingreso de una gran variedad de microorganismos. Cualquier alteración de la superficie ocular facilita la invasión bacteriana de la córnea. El germen más frecuentemente identificado es Staphylococcus aureus. Se presenta una paciente con enfermedad debida al virus de la inmunodeficiencia humana (VIH) con diagnóstico de sida, absceso corneal bilateral y lesiones cutáneas. S.aureus meticilino resistente se aisló en hemocultivos y en material obtenido por raspado de la córnea. El absceso corneal es una entidad poco frecuente en pacientes con infección por VIH y síndrome de inmunodeficiencia adquirida.

The corneal epithelium is an important defense barrier that prevents the entry of great variety of microorganisms. Any alteration of the ocular surface facilitates bacterial invasion of the cornea. The most frequently reported germ is Staphylococcus aureus. Here, we present a patient with a diagnosis of HIV/ AIDS disease, who developed bilateral corneal abscess and skin lesions. Methicillin-resistant Staphylococcus aureus was isolated from blood cultures and corneal scrapings. Corneal abscess is a rare entity in patients with HIV and acquired immunodeficiency syndrome