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Lignin solvated in zwitterionic Good's buffers displays antibacterial synergy against Staphylococcus aureus
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Structure and function of the bacillithiol- S -transferase BstA from Staphylococcus aureus : BstA Structure
Abstract not provided
Promoter-Specific Transcription Inhibition in Staphylococcus aureus by a Phage Protein
Abstract not provided
pSK41/pGO1-family conjugative plasmids of Staphylococcus aureus encode a cryptic repressor of replication
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Crystal and Solution Structure Analysis of FhuD2 from Staphylococcus aureus in Multiple Unliganded Conformations and Bound to Ferrioxamine-B
Abstract not provided
The Structural and Functional Basis for Recurring Sulfa Drug Resistance Mutations in Staphylococcus aureus Dihydropteroate Synthase
Staphylococcal species are a leading cause of bacterial drug-resistant infections and associated mortality. One strategy to combat bacterial drug resistance is to revisit compromised targets, and to circumvent resistance mechanisms using structure-assisted drug discovery. The folate pathway is an ideal candidate for this approach. Antifolates target an essential metabolic pathway, and the necessary detailed structural information is now available for most enzymes in this pathway. Dihydropteroate synthase (DHPS) is the target of the sulfonamide class of drugs, and its well characterized mechanism facilitates detailed analyses of how drug resistance has evolved. Here, we surveyed clinical genetic sequencing data in S. aureus to distinguish natural amino acid variations in DHPS from those that are associated with sulfonamide resistance. Five mutations were identified, F17L, S18L, T51M, E208K, and KE257_dup. Their contribution to resistance and their cost to the catalytic properties of DHPS were evaluated using a combination of biochemical, biophysical and microbiological susceptibility studies. These studies show that F17L, S18L, and T51M directly lead to sulfonamide resistance while unexpectedly increasing susceptibility to trimethoprim, which targets the downstream enzyme dihydrofolate reductase. The secondary mutations E208K and KE257_dup restore trimethoprim susceptibility closer to wild-type levels while further increasing sulfonamide resistance. Structural studies reveal that these mutations appear to selectively disfavor the binding of the sulfonamides by sterically blocking an outer ring moiety that is not present in the substrate. This emphasizes that new inhibitors must be designed that strictly stay within the substrate volume in the context of the transition state.
Concentrations of Staphylococcus species in indoor air as associated with other bacteria, season, relative humidity, air change rate, and S. aureus-positive occupants
The aim of this study was to obtain knowledge about concentrations of Staphylococcus aureus, MRSA (methicillin-resistant S. aureus), and other Staphylococcus species in indoor air in Greater Copenhagen and about factors affecting the concentrations. The effects of season, temperature, relative humidity, air change rate (ACR), other bacterial genera, area per occupant, and presence of S. aureus-positive occupants were studied. In samples from 67 living rooms, S. hominis, S. warneri, S. epidermidis, and S. capitis were found in 13–25%; S. saprophyticus, S. cohnii, and S. pasteuri in 5–10%; and S. lugdunensis, S. haemolyticus, S. caprae, S. equorum, S. kloosii, S. pettenkoferi, S. simulans, and S. xylosus in less than 3%. Staphylococcus aureus were found in two of 67 living rooms: spa type t034 (an MRSA) was recovered from a farmhouse, while spa type t509 was found in an urban home. Two species, S. equorum and S. kloosii, were found only in the farmhouse. Staphylococcus was significantly associated with season with lowest concentration and richness in winter. Genera composition was associated with ACR with smaller fractions of Staphylococcus at higher ACR, while richness was significantly and negatively associated with area per occupant. Concentration of Staphylococcus correlated positively with the total concentration of bacteria, but negatively with the total concentration of other bacteria. The concentration of Staphylococcus was not significantly associated with concentrations of the other abundant genera Bacillus, Kocuria, and Micrococcus. In offices with S. aureus-positive occupants, airborne S. aureus was not found. In conclusion, Staphylococcus species constitute a considerable proportion of the airborne bacteria in the studied homes and offices. However, both S. aureus and MRSA had very low prevalence during all seasons. Thus, transmission of S. aureus and MRSA through the air in living rooms in Copenhagen is expected to be limited. The negative associations between ACR and the fraction Staphylococcus constituted out of total bacteria, and between area per occupant and Staphylococcus richness indicate that it might be possible to affect the presence of airborne Staphylococcus in homes.
Staphylococcus-Infected Tunneled Dialysis Catheters: Is Over-the-Wire Exchange an Appropriate Management Option?
Purpose: Over-the-wire exchange of tunneled dialysis catheters is the standard of care per K/DOQI guidelines for treating catheter-related bacteremia. However, Gram-positive bacteremia, specifically with staphylococcus species, may compromise over-the-wire exchange due to certain biological properties. This study addressed the effectiveness of over-the-wire exchange of staphylococcus-infected tunneled dialysis catheters compared with non-staphylococcus-infected tunneled dialysis catheters. Methods: Patients who received over-the-wire exchange of their tunneled dialysis catheter due to documented or suspected bacteremia were identified from a QA database. Study patients (n = 61) had positive cultures for Staphylococcus aureus, Staphylococcus epidermidis, or coagulase-negative staphylococcus not otherwise specified. Control patients (n = 35) received over-the-wire exchange of their tunneled dialysis catheter due to infection with any organism besides staphylococcus. Overall catheter survival and catheter survival among staphylococcal species were assessed. Results: There was no difference in tunneled dialysis catheter survival between study and control groups (P = 0.46). Median survival time was 96 days for study catheters and 51 days for controls; survival curves were closely superimposed. There also was no difference among the three staphylococcal groups in terms of catheter survival (P = 0.31). The median time until catheter removal was 143 days for SE, 67 days for CNS, and 88 days for SA-infected catheters. Conclusions: There is no significant difference in tunneled dialysis catheter survival between over-the-wire exchange of staphylococcus-infected tunneled dialysis catheters and those infected with other organisms.
The Evaluation of Methicillin Resistance in Staphylococcus aboard the International Space Station
The International Space Station (ISS) represents a semi-closed environment with a high level of crewmember interaction. As community-acquired methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a health concern in environments with susceptible hosts in close proximity, an evaluation of isolates of clinical and environmental Staphylococcus aureus and coagulase negative Staphylococcus was performed to determine if this trend was also present in astronauts aboard ISS or the space station itself. Rep-PCR fingerprinting analysis of archived ISS isolates confirmed our earlier studies indicating a transfer of S. aureus between crewmembers. In addition, this fingerprinting also indicated a transfer between crewmembers and their environment. While a variety of S. aureus were identified from both the crewmembers and the environment, phenotypic evaluations indicated minimal methicillin resistance. However, positive results for the Penicillin Binding Protein, indicative of the presence of the mecA gene, were detected in multiple isolates of archived Staphylococcus epidermidis and Staphylococcus haemolyticus. Phenotypic analysis of these isolates confirmed their resistance to methicillin. While MRSA has not been isolated aboard ISS, the potential exists for the transfer of the gene, mecA, from coagulase negative environmental Staphylococcus to S. aureus creating MRSA strains. This study suggests the need to expand environmental monitoring aboard long duration exploration spacecraft to include antibiotic resistance profiling.
A Survey of Staphylococcus sp and its Methicillin Resistance aboard the International Space Station
Background: Within the past few years, methicillin-resistant Staphylococcus aureus has emerged in environments with susceptible hosts in close proximity, such as hospitals and nursing homes. As the International Space Station (ISS) represents a semi-closed environment with a high level of crewmember interaction, an evaluation of isolates of clinical and environmental Staphylococcus aureus and coagulase negative Staphylococcus was performed to determine if this trend was also present in astronauts occupying ISS or on surfaces of the space station itself. Methods: Identification of isolates was completed using VITEK (GPI cards, BioMerieux), 16S ribosomal DNA analysis (MicroSeq 500, ABI), and Rep-PCR DNA fingerprinting (Divemilab, Bacterial Barcodes). Susceptibility tests were performed using VITEK (GPS-105 cards, BioMerieux) and resistance characteristics were evaluated by testing for the presence of the mecA gene (PBP2' MRSA test kit, Oxoid). Results: Rep-PCR analysis indicated the transfer of S. aureus between crewmembers and between crewmembers and ISS surfaces. While a variety of S. aureus were identified from both the crewmembers and environment, evaluations of the microbial population indicated minimal methicillin resistance. Results of this study indicated that within the semi-closed ISS environment, transfer of bacteria between crewmembers and their environment has been occurring, although there was no indication of a high concentration of methicillin resistant Staphylococcus species. Conclusions: While this study suggests that the spread of methicillin resistant S. aureus is not currently a concern aboard ISS, the increasing incidence of Earth-based antibiotic resistance indicates a need for continued clinical and environmental monitoring.
Genomic analysis and identification of a novel superantigen, SargEY, in Staphylococcus argenteus isolated from atopic dermatitis lesions
During surveillance of Staphylococcus aureus in lesions from patients with atopic dermatitis (AD), we isolated Staphylococcus argenteus, a species registered in 2011 as a new member of the genus Staphylococcus and previously considered a lineage of S. aureus. Genome sequence comparisons between S. argenteus isolates and representative S. aureus clinical isolates from various origins revealed that the S. argenteus genome from AD patients closely resembles that of S. aureus causing skin infections. We previously reported that 17%–22% of S. aureus isolated from skin infections produce staphylococcal enterotoxin Y (SEY), which predominantly induces T-cell proliferation via the T-cell receptor (TCR) Vα pathway. Complete genome sequencing of S. argenteus isolates revealed a gene encoding a protein similar to superantigen SEY, designated as SargEY, on its chromosome. Population structure analysis of S. argenteus revealed that these isolates are ST2250 lineage, which was the only lineage positive for the SEY-like gene among S. argenteus. Recombinant SargEY demonstrated immunological cross-reactivity with anti-SEY serum. SargEY could induce proliferation of human CD4 + and CD8 + T cells, as well as production of TNF-α and IFN-γ. SargEY showed emetic activity in a marmoset monkey model. S arg EY and SET (a phylogenetically close but uncharacterized SE) revealed their dependency on TCR Vα in inducing human T-cell proliferation. Additionally, TCR sequencing revealed other previously undescribed Vα repertoires induced by SEH. S arg EY and SEY may play roles in exacerbating the respective toxin-producing strains in AD.
Comparative analysis of methicillin-sensitive and resistant Staphylococcus aureus exposed to emodin based on proteomic profiling
Highlights: • Emodin is effective against methicillin-sensitive and resistant Staphylococcus aureus strains. • Global proteomic profiling revealed 145 and 122 significant changes in MSSA and MRSA after emodin treatment, respectively. • Profiling interaction network analysis demonstrated emodin potentially targeted MRSA via multiple mechanisms. Emodin has a strong antibacterial activity, including methicillin-resistant Staphylococcus aureus (MRSA). However, the mechanism by which emodin induces growth inhibition against MRSA remains unclear. In this study, the isobaric tags for relative and absolute quantitation (iTRAQ) proteomics approach was used to investigate the modes of action of emodin on a MRSA isolate and methicillin-sensitive S. aureus ATCC29213(MSSA). Proteomic analysis showed that expression levels of 145 and 122 proteins were changed significantly in MRSA and MSSA, respectively, after emodin treatment. Comparative analysis of the functions of differentially expressed proteins between the two strains was performed via bioinformatics tools blast2go and STRING database. Proteins related to pyruvate pathway imbalance induction, protein synthesis inhibition, and DNA synthesis suppression were found in both methicillin-sensitive and resistant strains. Moreover, Interference proteins related to membrane damage mechanism were also observed in MRSA. Our findings indicate that emodin is a potential antibacterial agent targeting MRSA via multiple mechanisms.
Identification of small molecule compounds active against Staphylococcus aureus and Proteus mirabilis
Highlights: • Focused library screen identifies bacteriostatics of many pathogens. • Staphylococcus aureus' growth is inhibited at IC{sub 50} = 30–150 μM. • Proteus mirabilis is killed by similar compound chemical structures of compounds are different from known antibacterials. Staphylococcus aureus is a human pathogen rapidly becoming a serious health problem due to ease of acquiring antibiotic resistance. To help identify potential new drug candidates effective against the pathogen, a small focused library was screened for inhibition of bacterial growth against several pathogens, including S. aureus. At least one of the compounds, Compound 10, was capable of blocking bacterial growth of S. aureus in a test tube with IC{sub 50} = 140 ± 30 μM. Another inhibitor, Compound 7, was bacteriostatic against S. aureus with IC{sub 50} ranging from 33 to 150 μM against 3 different strains. However, only Compound 7 was bactericidal against P. mirabilis as examined by electron microscopy. Human cell line toxicity studies suggested that both compounds had small effect on cell growth at 100 μM concentration as examined by MTT assay. Analysis of compounds’ structures showed lack of similarity to any known antibiotics and bacteriostatics, potentially offering the inhibitors as an alternative to existing solutions in controlling bacterial infections for selected pathogens.
Staphylococcus pseudintermedius 5'-nucleotidase suppresses canine phagocytic activity
Staphylococcus pseudintermedius is a major opportunistic bacterial pathogen and the leading cause of pyoderma in dogs. In canines it is also often associated with infections of the urinary system and wounds and occasionally infects people. Widespread antimicrobial resistance has made the development of alternative treatments a high priority. The development of a staphylococcal vaccine, however, has proven challenging. Identification of virulence factors that inhibit phagocytosis and avoid innate immunity may play a significant role in preventing or treating infection with S. pseudintermedius. In this study, we identified a putative 5'-nucleotidase provisionally named SpAdsA, a S. pseudintermedius cell- wall protein encoded by SpAdsA. SpAdsA shares approximately 52% identity with the orthologous protein of Staphylococcus aureus and 14.8% identity with that of Streptococcus suis type2. It catalyzes the dephosphorylation of adenosine triphosphate and attenuation of this enzyme with critical amino acid substitutions nearly eliminated its hydrolytic activity. Furthermore, exogenous adenosine inhibited phagocytosis of S. pseudintermedius by canine neutrophils and monocytes. Conversely, the addition of SpAdsA inhibitor or A2A adenosine receptor antagonist impaired the capacity of S. pseudintermedius to escape from killing by phagocytic cells. The neutralizing ability of canine antibody produced against SpAdsA-M was determined. Taken together, these results suggest that SpAdsA likely plays an important role in S. pseudintermedius virulence and that attenuated SpAdsA may be a good candidate for inclusion in a vaccine against S. pseudintermedius.