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Vitamin A and its biologically active derivative, retinoic acid (RA), are important for many immune processes. RA, in particular, is essential for the development of immune cells, including neutrophils, which serve as a front-line defense against infection. While vitamin A deficiency has been linked to higher susceptibility to infections, the precise role of vitamin A/RA in host-pathogen interactions remains poorly understood. Here, we provided evidence that RA boosts neutrophil killing of methicillin-resistant Staphylococcus aureus (MRSA). RA treatment stimulated primary human neutrophils to produce reactive oxygen species, neutrophil extracellular traps, and the antimicrobial peptide cathelicidin (LL-37). Because RA treatment was insufficient to reduce MRSA burden in an in vivo murine model of skin infection, we expanded our analysis to other infectious agents. RA did not affect the growth of a number of common bacterial pathogens, including MRSA, Escherichia coli K1 and Pseudomonas aeruginosa; however, RA directly inhibited the growth of group A Streptococcus (GAS). This antimicrobial effect, likely in combination with RA-mediated neutrophil boosting, resulted in substantial GAS killing in neutrophil killing assays conducted in the presence of RA. Furthermore, in a murine model of GAS skin infection, topical RA treatment showed therapeutic potential by reducing both skin lesion size and bacterial burden. These findings suggest that RA may hold promise as a therapeutic agent against GAS and perhaps other clinically significant human pathogens.

UNLABELLED: Infections caused by Staphylococcus aureus are a leading cause of mortality worldwide. S. aureus infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are particularly difficult to treat due to their resistance to next-generation β-lactams (NGBs) such as methicillin, nafcillin, and oxacillin. Resistance to NGBs, which is alternatively known as broad-spectrum β-lactam resistance, is classically mediated by PBP2a, a penicillin-binding protein encoded by mecA (or mecC) in MRSA. Thus, presence of mec genes among S. aureus spp. serves as the predictor of resistance to NGBs and facilitates determination of the proper therapeutic strategy for a staphylococcal infection. Although far less appreciated, mecA-deficient S. aureus strains can also exhibit NGB resistance. These strains, which are collectively termed as methicillin-resistant lacking mec (MRLM), are currently being identified in increasing numbers among natural resistant isolates of S. aureus. The mechanism/s through which MRLMs produce resistance to NGBs remains unknown. In this study, we demonstrate that mutations that alter PBP4 and GdpP functions, which are often present among MRLMs, can synergistically mediate resistance to NGBs. Furthermore, our results unravel that this novel mechanism potentially enables MRLMs to produce resistance toward NGBs at levels comparable to those of MRSAs. Our study provides a fresh new perspective about alternative mechanisms of NGB resistance, challenging our current overall understanding of high-level, broad-spectrum β-lactam resistance in S. aureus. It thus suggests reconsideration of the current approach toward diagnosis and treatment of β-lactam-resistant S. aureus infections. IMPORTANCE: In Staphylococcus aureus, high-level, broad-spectrum resistance to β-lactams such as methicillin, also referred to as methicillin resistance, is largely attributed to mecA. This study demonstrates that S. aureus strains that lack mecA but contain mutations that functionally alter PBP4 and GdpP can also mediate high-level, broad-spectrum resistance to β-lactams. Resistance brought about by the synergistic action of functionally altered PBP4 and GdpP was phenotypically comparable to that displayed by mecA, as seen by increased bacterial survival in the presence of β-lactams. An analysis of mutations detected in naturally isolated strains of S. aureus revealed that a significant proportion of them had similar pbp4 and GGDEF domain protein containing phosphodiesterase (gdpP) mutations, making this study clinically significant. This study not only identifies important players of non-classical mechanisms of β-lactam resistance but also indicates reconsideration of current clinical diagnosis and treatment protocols of S. aureus infections.

The skin provides an essential barrier for host defense through rapid action of multiple resident and recruited cell types, but the complex communication network governing these processes is incompletely understood. To define these cell-cell interactions more clearly, we performed an unbiased network analysis of mouse skin during invasive S. aureus infection and revealed a dominant role for CXCL12+ fibroblast subsets in neutrophil communication. These subsets predominantly reside in the reticular dermis, express adipocyte lineage markers, detect IL-17 and TNFα, and promote robust neutrophil recruitment through NFKBIZ-dependent release of CXCR2 ligands and CXCL12. Targeted deletion of Il17ra in mouse fibroblasts resulted in greatly reduced neutrophil recruitment and increased infection by S. aureus. Analogous human CXCL12+ fibroblast subsets abundantly express neutrophil chemotactic factors in psoriatic skin that are subsequently decreased upon therapeutic targeting of IL-17. These findings show that CXCL12+ dermal immune acting fibroblast subsets play a critical role in cutaneous neutrophil recruitment and host defense.

Host-directed therapy (HDT) is an emerging approach to overcome antimicrobial resistance in pathogenic microorganisms. Specifically, HDT targets host-encoded factors required for pathogen replication and survival without interfering with microbial growth or metabolism, thereby eliminating the risk of resistance development. By applying HDT and a drug repurposing approach, we demonstrate that (R)-DI-87, a clinical-stage anticancer drug and potent inhibitor of mammalian deoxycytidine kinase (dCK), mitigates Staphylococcus aureus abscess formation in organ tissues upon invasive bloodstream infection. Mechanistically, (R)-DI-87 shields phagocytes from staphylococcal death-effector deoxyribonucleosides that target dCK and the mammalian purine salvage pathway-apoptosis axis. In this manner, (R)-DI-87-mediated protection of immune cells amplifies macrophage infiltration into deep-seated abscesses, a phenomenon coupled with enhanced pathogen control, ameliorated immunopathology, and reduced disease severity. Thus, pharmaceutical blockade of dCK represents an advanced anti-infective intervention strategy against which staphylococci cannot develop resistance and may help to fight fatal infectious diseases in hospitalized patients.

Skin microbiome can be altered in patients with atopic dermatitis (AD). An understanding of the changes from healthy to atopic skin can help develop new targets for treatment by identifying microbial and molecular biomarkers. This study investigates the skin microbiome and metabolome of healthy adult subjects and lesion (ADL) and non-lesion (ADNL) of AD patients by 16S rRNA gene sequencing and mass spectrometry, respectively. Samples from AD patients showed alterations in the diversity and composition of the skin microbiome, with ADL skin having the greatest divergence. Staphylococcus species, especially S. aureus, were significantly increased in AD patients. Metabolomic profiles were also different between the groups. Dipeptide derivatives are more abundant in ADL, which may be related to skin inflammation. Co-occurrence network analysis of the microbiome and metabolomics data revealed higher co-occurrence of metabolites and bacteria in healthy ADNL compared to ADL. S. aureus co-occurred with dipeptide derivatives in ADL, while phytosphingosine-derived compounds showed co-occurrences with commensal bacteria, for example, Paracoccus sp., Pseudomonas sp., Prevotella bivia, Lactobacillus iners, Anaerococcus sp., Micrococcus sp., Corynebacterium ureicelerivorans, Corynebacterium massiliense, Streptococcus thermophilus, and Roseomonas mucosa, in healthy and ADNL groups. Therefore, these findings provide valuable insights into how AD affects the human skin metabolome and microbiome.IMPORTANCEThis study provides valuable insight into changes in the skin microbiome and associated metabolomic profiles in an adult population with mild to moderate atopic dermatitis. It also identifies new therapeutic targets that may be useful for developing personalized treatments for individuals with atopic dermatitis based on their unique skin microbiome and metabolic profiles.

The failure of the Staphylococcus aureus (SA) IsdB vaccine trial can be explained by the recall of non-protective immune imprints from prior SA exposure. Here, we investigate natural human SA humoral imprints to understand their broader impact on SA immunizations. We show that antibody responses against SA cell-wall-associated antigens (CWAs) are non-opsonic, while antibodies against SA toxins are neutralizing. Importantly, the protective characteristics of the antibody imprints accurately predict the failure of corresponding vaccines against CWAs and support vaccination against toxins. In passive immunization platforms, natural anti-SA human antibodies reduce the efficacy of the human monoclonal antibodies suvratoxumab and tefibazumab, consistent with the results of their respective clinical trials. Strikingly, in the absence of specific humoral memory responses, active immunizations are efficacious in both naive and SA-experienced mice. Overall, our study points to a practical and predictive approach to evaluate and develop SA vaccines based on pre-existing humoral imprint characteristics.

BACKGROUND: Community-acquired Staphylococcus aureus (CA-Sa) skin and soft tissue infections (SSTIs) are historically associated with densely populated urban areas experiencing high poverty rates, intravenous drug use, and homelessness. However, the epidemiology of CA-Sa SSTIs in the United States has been poorly understood since the plateau of the Community-acquired Methicillin-resistant Staphylococcus aureus epidemic in 2010. This study examines the spatial variation of CA-Sa SSTIs in a large, geographically heterogeneous population and identifies neighborhood characteristics associated with increased infection risk. METHODS: Using a unique neighborhood boundary, California Medical Service Study Areas, a hotspot analysis, and estimates of neighborhood infection risk ratios were conducted for all CA-Sa SSTIs presented in non-Federal California emergency departments between 2016 and 2019. A Bayesian Poisson regression model evaluated the association between neighborhood-level infection risk and population structure, neighborhood poverty rates, and being a healthcare shortage area. RESULTS: Emergency departments in more rural and mountainous parts of California experienced a higher burden of CA-Sa SSTIs between 2016 and 2019. Neighborhoods with high infection rates were more likely to have a high percentage of adults living below the federal poverty level and be a designated healthcare shortage area. Measures of population structure were not associated with infection risk in California neighborhoods. CONCLUSIONS: Our results highlight a potential change in the epidemiology of CA-Sa SSTIs in California emergency departments. Future studies should investigate the CA-Sa burden in other geographies to identify whether this shift in epidemiology holds across other states and populations. Further, a more thorough evaluation of potential mechanisms for the clustering of infections seen across California neighborhoods is needed.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important zoonotic pathogen associated with a wide range of infections in humans and animals. Thus, the emergence of MRSA clones poses an important threat to human and animal health. This study is aimed at elucidating the genomics insights of a strong biofilm-producing and multidrug-resistant (MDR) S. aureus MTR_BAU_H1 strain through whole-genome sequencing (WGS). The S. aureus MTR_BAU_H1 strain was isolated from food handlers hand swabs in Bangladesh and phenotypically assessed for antimicrobial susceptibility and biofilm production assays. The isolate was further undergone to high throughput WGS and analysed using different bioinformatics tools to elucidate the genetic diversity, molecular epidemiology, sequence type (ST), antimicrobial resistance, and virulence gene distribution. Phenotypic analyses revealed that the S. aureus MTR_BAU_H1 strain is a strong biofilm-former and carries both antimicrobial resistance (e.g., methicillin resistance; mecA, beta-lactam resistance; blaZ and tetracycline resistance; tetC) and virulence (e.g., sea, tsst, and PVL) genes. The genome of the S. aureus MTR_BAU_H1 belonged to ST1930 that possessed three plasmid replicons (e.g., rep16, rep7c, and rep19), seven prophages, and two clustered regularly interspaced short palindromic repeat (CRISPR) arrays of varying sizes. Phylogenetic analysis showed a close evolutionary relationship between the MTR_BAU_H1 genome and other MRSA clones of diverse hosts and demographics. The MTR_BAU_H1 genome harbours 42 antimicrobial resistance genes (ARGs), 128 virulence genes, and 273 SEED subsystems coding for the metabolism of amino acids, carbohydrates, proteins, cofactors, vitamins, minerals, and lipids. This is the first-ever WGS-based study of a strong biofilm-producing and MDR S. aureus strain isolated from human hand swabs in Bangladesh that unveils new information on the resistomes (ARGs and correlated mechanisms) and virulence potentials that might be linked to staphylococcal pathogenesis in both humans and animals.

INTRODUCTION: Staphylococcus aureus bacteremia (SAB) is a life-threatening infection particularly involving methicillin-resistant S. aureus (MRSA). In contrast to resolving MRSA bacteremia (RB), persistent MRSA bacteremia (PB) blood cultures remain positive despite appropriate antibiotic treatment. Host immune responses distinguishing PB vs. RB outcomes are poorly understood. Here, integrated transcriptomic, IL-10 cytokine levels, and genomic analyses sought to identify signatures differentiating PB vs. RB outcomes. METHODS: Whole-blood transcriptomes of propensity-matched PB (n=28) versus RB (n=30) patients treated with vancomycin were compared in one independent training patient cohort. Gene expression (GE) modules were analyzed and prioritized relative to host IL-10 cytokine levels and DNA methyltransferase-3A (DNMT3A) genotype. RESULTS: Differential expression of T and B lymphocyte gene expression early in MRSA bacteremia discriminated RB from PB outcomes. Significant increases in effector T and B cell signaling pathways correlated with RB, lower IL-10 cytokine levels and DNMT3A heterozygous A/C genotype. Importantly, a second PB and RB patient cohort analyzed in a masked manner demonstrated high predictive accuracy of differential signatures. DISCUSSION: Collectively, the present findings indicate that human PB involves dysregulated immunity characterized by impaired T and B cell responses associated with excessive IL-10 expression in context of the DNMT3A A/A genotype. These findings reveal distinct immunologic programs in PB vs. RB outcomes, enable future studies to define mechanisms by which host and/or pathogen drive differential signatures and may accelerate prediction of PB outcomes. Such prognostic assessment of host risk could significantly enhance early anti-infective interventions to avert PB and improve patient outcomes.

Brodies abscess is a manifestation of subacute to chronic osteomyelitis, characterized as intraosseous abscess formation, usually on the metaphysis of the long tubular bones in the lower extremities of male pediatric patients. Clinically, Brodies abscess presents with atraumatic bone pain of an insidious onset, with absence of systemic findings. Delay in diagnosis is common, as diagnostic imaging, followed by biopsy for culture and histologic examination are generally required to secure a diagnosis of Brodies abscess. Treatment of Brodies abscess is non-standardized, and usually consists of surgical debridement and antibacterial therapy. Despite the variability in therapeutic approaches, outcomes of Brodies abscess treated with surgery and antibiotics are favourable. Herein we report a case of a delayed diagnosis of Brodies abscess in the upper extremity of an adult female. While she improved with treatment of Brodies abscess, the case serves to remind clinicians to consider this entity in adult individuals who present with atraumatic bone pain.

The purpose of this study was to establish a porcine model of urinary tract infection (UTI) with gram‐positive uropathogens. Ten female domestic pigs were experimentally inoculated with human UTI isolates of Enterococcus faecalis (n = 3), Staphylococcus saprophyticus (n = 3), or Staphylococcus aureus (n = 4) and followed with regular urine samples. Bladders and kidneys were aseptically removed at termination (5–7 days post infection) and assessed by gross pathology and bacterial enumeration. Enterococcus faecalis (n = 3 of 3) and S. aureus (n = 2 of 4) successfully colonized the pig bladders. Inoculation with S. saprophyticus never resulted in detectable bacteriuria. All infected pigs had cleared the infection spontaneously before termination. Surprisingly, three (of four) pigs inoculated with S. aureus led to spontaneous infection with opportunistic pathogens. Also, one pig colonized with E. faecalis resulted in spontaneous infection with E. coli. In conlusion, the pig supports experimental UTI with E. faecalis for up to 24 h but not prolonged infection. S. aureus and S. saprophyticus fails to cause UTI in pigs and other animals should be considered for studying these pathogens. [ABSTRACT FROM AUTHOR]

Introduction: Orthodontic clear aligners and retainers have numerous advantages that is making them ever increasingly popular. However, they might, similar to any other oral appliance, contribute to biofilm formation and finally dental caries or white spot lesions or gingival inflammations. The literature on biofilm formation on orthodontic clear appliances is very scarce and limited to a few microorganisms and materials. Therefore, this experimental study evaluated the biofilm formation on 5 thermoformed and 3D printed CAD/CAM orthodontic retainers in 3 intervals. Methods: In this in vitro study, 345 specimens (270 test discs and 45 negative controls) were created from fabricated retainers. Retainers included a 3D printed CAD/CAM material (Detax) and four thermoformed retainers [Erkodent (polyethylene terephthalate glycol [PETG]); EasyVac (polyethylene); DB (polyester based on terephthalic acid); and Clear Tech]. They were all 1 mm thick, and all completely fabricated, i.e., heated or printed. The discs were placed in 96-well plates. Microorganisms were cultured on 270 discs for 24 h (90 discs), 72 h (90 other discs), and 5 days or 120 h (90 other discs). Biofilm formation of the strains and negative controls was measured using the microtiter plate assay by ELISA reading. The microbes' ability to produce biofilm was categorized based on the comparison of average optical density (OD) of tests versus a cut-off point OD (ODc) calculated as the average of the OD of corresponding negative controls plus 3× its standard deviation: non-biofilm former [OD ≤ ODc], weak biofilm former [ODc < OD ≤ (2 × ODc)], moderate biofilm former [(2 × ODc) < OD ≤ (4 × ODc)], and strong biofilm former [(4 × ODc) < OD]. These were also converted to ranked scores between zero (no biofilm) and 3. The difference between ODs with control ODs were calculated. These were analyzed using 3-way ANOVA, 2-way ANOVA, and Tukey tests (α = 0.05, α = 0.008). Results: The 3-way ANOVA showed that the overall difference among the ΔODs of 5 retainers (all microorganisms and all intervals combined, n = 270) was not significant (F = 1.860, P = 0.119). Nevertheless, the difference among 3 intervals (F = 31.607, P = 0.0000) and the difference among the 6 microorganisms (F = 24.044, P = 0.0000) were significant. According to the Tukey test, the differences between the 1st interval with either of the other two intervals was significant (both P values = 0.000). There were significant differences between Candida albicans with all other organisms (all 5 P values = 0.0000). All other pairwise comparisons were insignificant (all 10 P values ≥ 0.1). After taking the averages of the 3 intervals, the order of the biofilm generation for different materials were as follows: Detax (average score: 1.56), Easyvac (1.67), Erkodent (1.78), Clear Tech (1.83), BD (2.28). Conclusions: As far as these 6 microorganisms are of concern, there might not be a significant overall difference among the clear retainer materials tested in this study. A significant overall increase was observed between the first and third days, which later did not significantly increase more until day 5. The Candida albicans biofilm was more intense than the tested 5 bacteria, which themselves showed rather similar growth patterns to each other. [ABSTRACT FROM AUTHOR]

Biofilm formation by Staphylococcus aureus is a major challenge in clinical settings due to its role in persistent infections. The AgrA protein, a key regulator in biofilm development, is a promising target for therapeutic intervention. This study investigates the antibiofilm potential of halogenated phenazine compounds by targeting AgrA and explores their molecular interactions to provide insights for drug development. We employed molecular docking, molecular dynamics simulations, and computational mutagenesis to evaluate the binding of halogenated phenazine compounds (C1 to C7, HP, and HP‐14) to AgrA. Binding free energy analysis was performed to assess the affinity of these compounds for the AgrA‐DNA complex. Additionally, the impact of these compounds on AgrA's structural conformation and salt bridge interactions was examined. The binding‐free energy analysis revealed that all compounds enhance binding affinity compared to the Apo form of AgrA, which has a ΔGbind of −80.75 kcal/mol. The strongest binding affinities were observed with compounds C7 (−113.84 kcal/mol), HP‐14 (−115.23 kcal/mol), and HP (−112.28 kcal/mol), highlighting their effectiveness. Molecular dynamics simulations demonstrated that these compounds bind at the hydrophobic cleft of AgrA, disrupting essential salt bridge interactions between His174‐Glu163 and His174‐Glu226. This disruption led to structural conformational changes and reduced DNA binding affinity, aligning with experimental findings on biofilm inhibition. The halogenated phenazine compounds effectively inhibit biofilm formation by targeting AgrA, disrupting its DNA‐binding function. The study supports the potential of these compounds as antibiofilm agents and provides a foundation for rational drug design targeting the AgrA‐DNA interaction. Future research should focus on further optimizing these lead compounds and exploring additional active sites on AgrA to develop novel treatments for biofilm‐associated infections. [ABSTRACT FROM AUTHOR]

Macrophages and osteocytes are important regulators of inflammation, osteogenesis and osteoclastogenesis. However, their interactions under adverse conditions, such as biomaterial-associated infection (BAI) are not fully understood. We aimed to elucidate how factors released from macrophages modulate osteocyte responses in an in vitro indirect 3D co-culture model. Human monocyte-derived macrophages were cultured on etched titanium disks and activated with either IL-4 cytokine (anti-inflammatory M2 phenotype) or Staphylococcus aureus secreted virulence factors to simulate BAI (pro-inflammatory M1 phenotype). Primary osteocytes in collagen gels were then stimulated with conditioned media (CM) from these macrophages. The osteocyte response was analyzed by gene expression, protein secretion, and immunostaining. M1 phenotype macrophages were confirmed by IL-1β and TNF-α secretion, and M2 macrophages by ARG-1 and MRC-1. Osteocytes receiving M1 CM revealed bone inhibitory effects, denoted by reduced secretion of bone formation osteocalcin (BGLAP) and increased secretion of the bone inhibitory sclerostin (SOST). These osteocytes also downregulated the pro-mineralization gene PHEX and upregulated the anti-mineralization gene MEPE. Additionally, exhibited pro-osteoclastic potential by upregulating pro-osteoclastic gene RANKL expression. Nonetheless, M1-stimulated osteocytes expressed a higher level of the potent pro-osteogenic factor BMP-2 in parallel with the downregulation of the bone inhibitor genes DKK1 and SOST , suggesting a compensatory feedback mechanisms. Conversely, M2-stimulated osteocytes mainly upregulated anti-osteoclastic gene OPG expression, suggesting an anti-catabolic effect. Altogether, our findings demonstrate a strong communication between M1 macrophages and osteocytes under M1 (BAI)-simulated conditions, suggesting that the BAI adverse effects on osteoblastic and osteoclastic processes in vitro are partly mediated via this communication. Biomaterial-associated infections are major challenges and the underlying mechanisms in the cellular interactions are missing, especially among the major cells from the inflammatory side (macrophages as the key cell in bacterial clearance) and the regenerative side (osteocyte as main regulator of bone). We evaluated the effect of macrophage polarization driven by the stimulation with bacterial virulence factors on the osteocyte function using an indirect co-culture model, hence mimicking the scenario of a biomaterial-associated infection. The results suggest that at least part of the adverse effects of biomaterial associated infection on osteoblastic and osteoclastic processes in vitro are mediated via macrophage-to-osteocyte communication. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: One effective method to combat bacterial infections is by using bacteria itself as a weapon. Lactobacillus is a type of fermenting bacterium that has probiotic properties and has demonstrated antimicrobial benefits against other bacteria. Cyclodipeptides (CDPs), present in the supernatant of Lactobacillus, possess several antimicrobial properties. Methods: In this study, the CDP fraction was isolated from the supernatant of Lactobacillus plantarum (L. plantarum). This fraction was then loaded onto graphene oxide nanosheets (GO NSs). The study assessed the substance’s ability to inhibit bacterial growth by using the minimum inhibitory concentration (MIC) method on A. baumannii and S. aureus strains that were obtained from clinical samples. To determine the substance’s impact on biofilm formation, the microtiter plate method was used. Moreover, the checkerboard technique was employed to explore the potential synergistic effects of these two substances. Results and discussion: According to the study, the minimum inhibitory concentration (MIC) of the desired compound was found to be 1.25  mg/ mL against S. aureus and 2.5  mg/mL against A. baumannii. Furthermore, at a concentration of 10  mg/mL, the compound prevented 81.6% (p  <  0.01) of biofilm production in A. baumannii, while at a concentration of 1.25  mg/mL, it prevented 47.5% (p  <  0.05) of biofilm production in S. aureus. The study also explored the synergistic properties of two compounds using the checkerboard method. Conclusion: In general, we found that GO NSs possess antimicrobial properties and enhance cyclodipeptides’ activity against S. aureus and A. baumannii. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (S. aureus) infection is a primary cause of otitis media (OM), the most common disease for which children are prescribed antibiotics. However, the abuse of antibiotics has led to a global increase in antimicrobial resistance (AMR). Nanozymes, as promising alternatives to traditional antibiotics, are being extensively utilized to combat AMR. Here, we synthesize a series of single-atom nanozymes (metal-C3N4 SANzymes) by loading four metals (Ag, Fe, Cu, Ru) with antibacterial properties onto a crystalline g-C3N4. These metal-C3N4 display a rob-like morphology and well-dispersed metal atoms. Among them, Ru-C3N4 demonstrates the optimal peroxidase-like activity (285.3 U mg-1), comparable to that of horseradish peroxidase (267.7 U mg-1). In vitro antibacterial assays reveal that Ru-C3N4 significantly inhibits S. aureus growth compared with other metal-C3N4 even at a low concentration (0.06 mg mL-1). Notably, Ru-C3N4 acts as a narrow-spectrum nanoantibiotic with relative specificity against Gram-positive bacteria. Biofilms formed by S. aureus are easily degraded by Ru-C3N4 due to its high peroxidase-like activity. In vivo, Ru-C3N4 effectively eliminates S. aureus and relieves ear inflammation in OM mouse models. However, untreated OM mice eventually develop hearing impairment. Due to its low metal load, Ru-C3N4 does not exhibit significant toxicity to blood, liver, or kidney. In conclusion, this study presents a novel SANzyme-based antibiotic that can effectively eliminate S. aureus and treat S. aureus-induced OM. [ABSTRACT FROM AUTHOR]

Antibacterial resistance requires an advanced strategy to increase the efficacy of current therapeutics in addition to the synthesis of new generations of antibiotics. In this study, copper oxide nanoparticles (CuO-NPs) were green synthesized using Moringa oleifera root extract. CuO-NPs fabricated into a form of aspartic acid-ciprofloxacin-polyethylene glycol coated copper oxide-nanotherapeutics (CIP-PEG-CuO) to improve the antibacterial activity of NPs and the efficacy of the drug with controlled cytotoxicity. These NPs were charachterized by Fourier transform infrared spectroscopy (FTIR), x-rays diffraction spectroscopy (XRD), scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS). Antibacterial screening and bacterial chemotaxis investigations demonstrated that CIP-PEG-CuO NPs show enhanced antibacterial potential against Gram-positive and Gram-negative clinically isolated pathogenic bacterial strains as compared to CuO-NPs. In ex-vivo cytotoxicity CIP-PEG-CuO-nano-formulates revealed 88% viability of Baby Hamster Kidney 21 cell lines and 90% RBCs remained intact with nano-formulations during hemolysis assay. An in-vivo studies on animal models show that Staphylococcus aureus were eradicated by this newly developed formulate from the infected skin and showed wound-healing properties. By using specially designed nanoparticles that are engineered to precisely transport antimicrobial agents, these efficient nano-drug delivery systems can target localized infections, ensure targeted delivery, enhance efficacy through increased drug penetration through physical barriers, and reduce systemic side effects for more effective treatment. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus is an infectious bacterium that is frequently found in healthcare settings and the community. This study aimed to prepare rutin-loaded chitosan nanoparticles (Rut-CS NPs) and assess their antibacterial activity against pathogenic strains of S. aureus. Results: The synthesized Rut-CS NPs exhibited an amorphous morphology with a size ranging from 160 to 240 nm and a zeta potential of 37.3 mV. Rut-CS NPs demonstrated significant antibacterial activity against S. aureus strains. Following exposure to Rut-CS NPs, the production of staphyloxanthin pigment decreased by 43.31–89.63%, leading to increased susceptibility of S. aureus to hydrogen peroxide. Additionally, visual inspection of cell morphology indicated changes in membrane integrity and permeability upon Rut-CS NPs exposure, leading to a substantial increase (107.07–191.08%) in cytoplasmic DNA leakage in the strains. Furthermore, ½ MIC of Rut-CS NPs effectively inhibited the biofilm formation (22.5–37.5%) and hemolytic activity (69–82.59%) in the S. aureus strains. Conclusions: Our study showcases that Rut-CS NPs can serve as a novel treatment agent to combat S. aureus infections by altering cell morphology and inhibiting virulence factors of S. aureus. [ABSTRACT FROM AUTHOR]

The emerging field of green synthesis within nanobiotechnology presents significant environmental and economic advantages compared to conventional methodologies. This study investigates the synthesis and application of chitosan nanoparticles (ChNPs) using Cassia fistula (CF) leaf extract as a sustainable, and bio-based approach. Characterization of CF-ChNPs confirmed effective bioconversion and also demonstrated significant antimicrobial activity. Notably, CF-ChNPs demonstrated a remarkable antimicrobial effect against Pseudomonas aeruginosa, with a zone of inhibition of 17 ± 0.2 mm surpassing the impact on other organisms tested. The CF-ChNPs exhibited an initial burst release of 28 ± 0.28% after 2 h, gradually achieving a controlled release of 76.3 ± 0.43% within 24 h. In addition, CF-ChNPs exhibited an antioxidant activity of 43.1 ± 0.48% and showed excellent antibiofilm activity against Staphylococcus aureus in comparison to other organisms. The cell viability assay results have confirmed that CF-ChNPs do not have any negative impact on the viability of L929 fibroblasts, further highlighting their potential as versatile nanomaterials for treating microbial infections and other therapeutic applications. [ABSTRACT FROM AUTHOR]

In March 2023, our pediatric intensive care unit (PICU) retrospectively examined six cases of pediatric necrotizing tracheobronchitis (NTB), focusing on co-infections with influenza A virus (IAV) and Staphylococcus aureus (S. aureus). This study aimed to elucidate NTB's clinical characteristics, diagnostics, and therapeutic approaches. Diagnostics included symptom assessment, microbiological testing that confirmed all patients were positive for IAV H1N1 with a predominant S. aureus co-infection, and bronchoscopy. The patients predominantly exhibited fever, cough, and dyspnea. Laboratory analysis revealed decreased lymphocyte counts and elevated infection markers like C-reactive protein and procalcitonin. Chest computed tomography (CT) scans detected tracheobronchial obstructions in half of the cases, while bronchoscopy showed severe mucosal congestion, edema, necrosis, and purulent-hemorrhagic exudates. Treatments encompassed comprehensive strategies like oxygen therapy, intubation, bronchoscopic interventions, thoracentesis, oseltamivir, and a regimen of antibiotics. Our findings suggested potential correlations between clinical markers, notably lymphocyte count and procalcitonin, and clinical interventions such as the number of rescues and intensive care unit (ICU) duration. This research highlights the importance of early detection and the role of bronchoscopy and specific markers in assessing NTB, advocating for continued research in larger cohorts to better understand its clinical trajectory and refine treatment approaches for this challenging pediatric disease. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusion Intubated patients with methicillin‐resistant Staphylococcus aureus pneumonia, fail optimized treatment with intravenous (IV) vancomycin (serum trough 15–20 μg/mL) in 38–79% of cases. Airway blood flow is diminished compared to alveoli and we hypothesized that vancomycin concentrations achieved in airway secretions are suboptimal and nonbactericidal. Targeted therapy by inhalation may overcome this deficit.Airway pharmacokinetics of optimized IV and inhaled vancomycin in infected clinically stable prolonged mechanically ventilated patients were measured. First, IV vancomycin was given until optimized concentrations were achieved (15–20 μg/mL), and, at the same time point, sputum vancomycin concentrations were measured. Then, sputum concentrations were re‐assessed after 4 treatments of inhaled vancomycin (120 mg/2 mL) via a previously characterized nebulizing system that deposited 18 ± 2 mg in the lungs. Vancomycin post‐distribution phase serum peak and trough concentrations were also obtained. Serum albumin was measured to assess binding to vancomycin.Mean serum trough concentration was 18.4 ± 6.5 μg/mL. Sputum concentrations were affected by serum albumin. Only patients with severe hypoalbuminaemia had penetration of drug leading to therapeutic (15.7–17 μg/mL) sputum concentrations. Following inhaled vancomycin, sputum concentrations increased significantly to 199 ± 37.0 μg/mL (P = .002) exceeding minimum inhibitory concentration by 2 orders of magnitude.Despite optimized serum concentrations, patients with albumin near normal had suboptimal concentrations of vancomycin in their sputum. Inhaled therapy may be clinically important for successful treatment of ventilator‐associated methicillin‐resistant Staphylococcus aureus infection. Further studies of inhaled therapy are needed to define their role as adjunctive therapy in ventilator‐associated pneumonia and as single therapy in tracheobronchitis. [ABSTRACT FROM AUTHOR]

Introduction: Antimicrobial-resistant pathogens present an ongoing threat to human and animal health, with deaths linked to antimicrobial resistance (AMR) predicted to increase annually. While the misuse and overuse of antibiotics in humans undoubtedly contribute to this escalation, antibiotic use in the veterinary field, including companion animals, also plays a contributing role. Pet owners' desire to improve the quality of life of their pets is likely to support antibiotic use in this field. Consequently, there is a need for antibiotic alternatives to treat bacterial infections. This study set out to screen for antimicrobial peptides known as bacteriocins from bacterial isolates of aerobic/ microaerophilic environments of canine sources and determine their potential as antibiotic alternatives against clinically relevant pathogens. Methods: Following a laboratory-based protocol, 22 bacterial isolates were subjected to whole-genome sequencing (WGS), and a total of 14 putative novel bacteriocins were identified from both class I and II bacteriocin classes. One particular bacteriocin, herein named caledonicin, was identified via in silico analysis from a Staphylococcus caledonicus strain and partially purified for further in vitro evaluation. Results: Caledonicin is a 64-amino acid (IAANLGVSSGTAYS MANALNNISNVATA LTIIGTFTGVGTIGSGIA ATILAILKKKGVAAAAAF) novel circular bacteriocin most closely related to enterocin_NKR-5-3B based on core peptide alignment (39.1%), with a molecular weight of 6077.1 Da. Caledonicin exhibits a broad-spectrum of activity against a range of pathogenic bacteria, including methicillinresistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus pseudintermedius (MRSP), and Listeria monocytogenes; and the gut-related bacterium associated with Crohn's disease, Mediterraneibacter gnavus ATCC 29149 (previously Ruminococcus gnavus ATCC 29149). Discussion: This represents the first bacteriocin screening study involving bacteria from canine sources and confirms this is a rich environment for bacteriocin-producing strains. This study also identifies and characterises the first novel bacteriocin from the staphylococcal species, Staphylococcus caledonicus. [ABSTRACT FROM AUTHOR]

Introduction: Despite years of efforts to develop new antibiotics for eradicating multidrug-resistant (MDR) and multi-virulent Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Staphylococcus aureus (VRSA) infections, treatment failures and poor prognoses in most cases have been common. Therefore, there is an urgent need for new therapeutic approaches targeting virulence arrays. Our aim is to discover new anti-virulence therapies targeting MRSA and VRSA virulence arrays. Methodology: We employed phenotypic, molecular docking, and genetic studies to screen for anti-virulence activities among selected promising compounds: Coumarin, Simvastatin, and Ibuprofen. Results: We found that nearly all detected MRSA and VRSA strains exhibited MDR and multi-virulent profiles. The molecular docking results aligned with the phenotypic and genetic assessments of virulence production. Biofilm and hemolysin productions were inhibited, and all virulence genes were downregulated upon treatment with sub-minimum inhibitory concentration (sub-MIC) of these promising compounds. Ibuprofen was the most active compound, exhibiting the highest inhibition and downregulation of virulence gene products. Moreover, in vivo and histopathological studies confirmed these results. Interestingly, we observed a significant decrease in wound area and improvements in re-epithelialization and tissue organization in the Ibuprofen and antimicrobial treated group compared with the group treated with antimicrobial alone. These findings support the idea that a combination of Ibuprofen and antimicrobial drugs may offer a promising new therapy for MRSA and VRSA infections. Conclusion: We hope that our findings can be implemented in clinical practice to assist physicians in making the most suitable treatment decisions. [ABSTRACT FROM AUTHOR]

Blending modification is used to improve the hemocompatibility of cellulose acetate (CA) dialysis membranes while endowing the CA membrane with endotoxin scavenging and antibacterial capabilities. First, polydopamine (PDA) and polyethylenimine (PEI) are used as negatively charged and positively charged moieties, respectively, together with cellulose nanocrystals (CNCs) to construct mixed charge CNCs (PEI‐PDA@CNCs). Then PEI‐PDA@CNCs is blended with the CA casting solution, and the modified CA dialysis membrane is prepared through a phase inversion process. Through biocompatibility, adsorption, antibacterial, and filtration experiments, various properties of PEI‐PDA@CNCs modified CA membrane (PDCA) are systematically tested. The results show that the PDCA membrane exhibited good blood compatibility and noncytotoxicity. At the same time, the PDCA membrane has antibacterial properties and excellent endotoxin adsorption capacity. Compared with the CA membrane, the clearance rates of PDCA membrane for Staphylococcus aureus and Escherichia coli reach 54.0% ± 1.5% and 52.9% ± 5.9% respectively. In the dynamic adsorption experiment, the adsorption capacity of PDCA membrane for endotoxin increases to 2322.1 ± 45.9 EU/g. The research results indicate that PEI‐PDA@CNC‐modified multifunctional CA membrane with endotoxin adsorption and antibacterial properties has potential application prospects in the fields of hemodialysis and blood purification. [ABSTRACT FROM AUTHOR]

Background: Aortic valve infective endocarditis (IE) is associated with significant morbidity and mortality. We aimed to describe the clinical profile, risk factors and predictors of short- and long-term mortality in patients with aortic valve IE treated with aortic valve replacement (AVR) compared with a control group undergoing AVR for non-infectious valvular heart disease. Methods: Between January 2008 and December 2013, a total of 170 cases with IE treated with AVR (exposed cohort) and 677 randomly selected non-infectious AVR-treated patients with degenerative aortic valve disease (controls) were recruited from three tertiary hospitals with cardiothoracic facilities across Scandinavia. Crude and adjusted hazard ratios (HR) were estimated using Cox regression models. Results: The mean age of the IE cohort was 58.5 ± 15.1 years (80.0% men). During a mean follow-up of 7.8 years (IQR 5.1-10.8 years), 373 (44.0%) deaths occurred: 81 (47.6%) in the IE group and 292 (43.1%) among controls. Independent risk factors associated with IE were male gender, previous heart surgery, underweight, positive hepatitis C serology, renal failure, previous wound infection and dental treatment (all p < 0.05). IE was associated with an increased risk of both short-term (≤ 30 days) (HR 2.86, [1.36–5.98], p = 0.005) and long-term mortality (HR 2.03, [1.43–2.88], p < 0.001). In patients with IE, chronic obstructive pulmonary disease (HR 2.13), underweight (HR 4.47), renal failure (HR 2.05), concomitant mitral valve involvement (HR 2.37) and mediastinitis (HR 3.98) were independent predictors of long-term mortality. Staphylococcus aureus was the most prevalent microbe (21.8%) and associated with a 5.2-fold increased risk of early mortality, while enterococci were associated with the risk of long-term mortality (HR 1.78). Conclusions: In this multicenter case-control study, IE was associated with an increased risk of both short- and long-term mortality compared to controls. Efforts should be made to identify, and timely treat modifiable risk factors associated with contracting IE, and mitigate the predictors of poor survival in IE. [ABSTRACT FROM AUTHOR]

Rapid and accurate bacterial identification is essential for timely treatment of infections like sepsis. While traditional methods are reliable, they lack speed, and advanced molecular techniques often suffer from cost and complexity. The bacterial detection technology based on optical scattering system offers a rapid, label-free alternative but traditionally relies on complex lasers and analysis. Our enhanced approach utilizes RGB light emitting diodes (LEDs) as the light source. Three diffraction images of bacterial colonies from different LED colors are separately captured by a USB camera and combined using an image registration algorithm to enhance image sharpness. Our approach utilizes an object detection model, i.e., YOLOv8, for analysis achieving high-accuracy differentiation between bacterial strains. We demonstrate the effectiveness of this approach, achieving an average accuracy of 97% (mAP50 of 0.97), including accurate discrimination of closely related strains and the significant pathogen Staphylococcus aureus MRSA 1320. Our enhancement offers advantages in affordability, usability, and seamless integration into existing workflows, providing an alternative for rapid bacterial identification. [ABSTRACT FROM AUTHOR]

Phenol soluble modulins (PSMs) are small amphipathic peptides involved in a series of biological functions governing staphylococcal pathogenesis, primarily by facilitating the formation of an extracellular fibril structure with amyloid-like properties. This fibrillar architecture stabilizes the staphylococcal biofilm making it resilient to antibiotic treatment. Our study aims to abrogate the amyloid fibrillation of PSM α1 with novel insights on the amyloid modulatory potential of a prenylated chalcone, Isobavachalcone (IBC). A combination of biophysical and computational assays to address the amyloid modulatory effect of IBC has been undertaken to arrive at a model for the inhibition of PSM α1 fibrillation. ThT kinetics studies indicated that IBC must be stably interacting with the amyloidogenic core of PSM α1 monomers or it may be inhibiting the pre-fibrillar aggregates populated at the early stages of amyloid transformation kinetics. This heteromolecular association further inhibits the amyloid transformation corroborated by a ∼ 94% and ∼ 91% reduction in the ThT maxima, even at sub-stoichiometric concentrations. Transmission electron microscopy (TEM) of end-stage aggregates (∼ 55 h) depict mature, inter-twined, laterally stacked amyloid fibrils in untreated PSM α1 samples while this fibrillar load is remarkably reduced in the presence of IBC. The inhibitory effect of IBC on the β-sheet transitions of PSM α1 were also validated using far-UV CD spectra. Molecular dynamics simulation studies with PSM aggregates (PSM-A) have also suggested that IBC disrupts the hydrogen bonding interactions and corroborates the inhibition of alpha to beta transitions of PSM-A. Collectively, our data proposes a novel structural motif for the rational discovery of non-toxic therapeutic agents targeting the functional amyloids which have slowly emerged as potent factors, consolidating the antibiotic resistant staphylococcal biofilm assembly. [ABSTRACT FROM AUTHOR]

Introduction: Both the incidence and mortality rates associated with methicillin-resistant Staphylococcus aureus (MRSA) have progressively increased worldwide. A nucleic acid testing system was developed in response, enabling swift and precise detection of Staphylococcus aureus (S. aureus) and its MRSA infection status. This facilitates improved prevention and control of MRSA infections. Methods: In this work, we introduce a novel assay platform developed by integrating Pyrococcus furiosus Argonaute (PfAgo) with recombinase polymerase amplification (RPA), which was designed for the simultaneous detection of the nuc and mecA genes in MRSA. Results: This innovative approach enables visual MRSA detection within 55 mins, boasting a detection limit of 10² copies/μL. Characterized by its high specificity, the platform accurately identifies MRSA infections without cross-reactivity to other clinical pathogens, highlighting its unique capability for S. aureus infection diagnostics amidst bacterial diversity. Validation of this method was performed on 40 clinical isolates, demonstrating a 95.0% accuracy rate in comparison to the established Vitek2-COMPACT system. Discussion: The RPA-PfAgo platform has emerged as a superior diagnostic tool, offering enhanced sensitivity, specificity, and identification efficacy for MRSA detection. Our findings underscore the potential of this platform to significantly improve the diagnosis and management of MRSA infection. [ABSTRACT FROM AUTHOR]

Importance: Staphylococcus aureus frequently colonizes the skin and nose of patients with atopic dermatitis (AD), a disease associated with skin barrier dysfunction and chronic cutaneous inflammation. Published genomic studies on AD-associated S. aureus in pediatric populations in sub-Saharan Africa are limited. Objectives: To investigate the phenotypic and genomic diversity of S. aureus in children with and without AD during early childhood. Data, setting and participants: A cross-sectional study of 220 children (aged 9-38 months) with AD (cases) and without AD (controls) from Cape Town and Umtata, South Africa. Main outcomes and measures: S. aureus phenotypic and genomic diversity were investigated using whole-genome sequencing, antibiotic susceptibility testing and biofilm microtiter assay. Results: Of the 124 S. aureus isolates recovered from 220 children, 96 isolates (79 cases and 17 controls) with high-quality sequences were analyzed. Isolates from cases showed greater phenotypic resistance to gentamicin (10%), rifampicin (4%), chloramphenicol (4%), and exhibited multidrug resistance (9%) than in controls. Furthermore, the isolates from cases formed stronger biofilms than those from controls (76% vs. 35%, p = 0.001), but showed no dominance of any virulence factor gene or mobile genetic elements. There was no significant difference in the distribution of immune evasion cluster types between cases and controls. However, IEC type G was identified only among cases. Conclusion and relevance: AD-associated S. aureus has phenotypic and genetic features that are important for successful pathogenic colonization and survival. Further studies are needed to assess the pathological implications of colonization of various S. aureus lineages in vivo to elucidate their pathological contribution to AD pathogenesis and pathophysiology. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (S. aureus) is a common foodborne pathogen, posing a serious threat to public health. Consequently, it is crucial to establish a platform for sensitive and specific determination of S. aureus in food. Herein, phage SapYZUH5, isolated by our lab, was covalently immobilized on Co3O4 to synthesize SapYZUH5@Co3O4. Notably, SapYZUH5@Co3O4 exhibited remarkable oxidase-like activity, enabling the catalysis of dissolved oxygen to generate superoxide anion free radicals and accelerate the TMB chromogenic reaction. Upon introduction of S. aureus, specific capture by SapYZUH5@Co3O4 resulted in inhibiting its oxidase-like activity and decelerating the 3,3′,5,5′-tetramethylbenzidine (TMB) chromogenic reaction. Moreover, S. aureus can be lysed to release the reductive bacterial contents, which can further inhibit the TMB chromogenic reaction. Based on this principle, SapYZUH5@Co3O4 + TMB reaction system was employed for detection with enhanced sensitivity of S. aureus, yielding an equation: A = − 0.092 Log (CSA) + 0.79 (R2 = 0.987), with an ultralow limit of detection (LOD) of 28 CFU mL−1. This system exhibited remarkable specificity and anti-interfere towards S. aureus, owing to the excellent affinity of SapYZUH5 towards S. aureus. In addition, S. aureus in the actual food samples was detected using this system, yielding recoveries ranging from 96.34 to 109.43%, demonstrating its exceptional accuracy. Hence, our proposed covalent immobilization of phage on the nanozyme can realize sensitive and specific colorimetric determination of S. aureus in food samples. [ABSTRACT FROM AUTHOR]

Bicarbonate and CO2 are essential substrates for carboxylation reactions in bacterial central metabolism. In Staphylococcus aureus, the bicarbonate transporter, MpsABC (membrane potential-generating system) is the only carbon concentrating system. An mpsABC deletion mutant can hardly grow in ambient air. In this study, we investigated the changes that occur in S. aureus when it suffers from CO2/bicarbonate deficiency. Electron microscopy revealed that ΔmpsABC has a twofold thicker cell wall thickness compared to the parent strain. The mutant was also substantially inert to cell lysis induced by lysostaphin and the non-ionic surfactant Triton X-100. Mass spectrometry analysis of muropeptides revealed the incorporation of alanine into the pentaglycine interpeptide bridge, which explains the mutant's lysostaphin resistance. Flow cytometry analysis of wall teichoic acid (WTA) glycosylation patterns revealed a significantly lower α-glycosylated and higher ß-glycosylated WTA, explaining the mutant's increased resistance towards Triton X-100. Comparative transcriptome analysis showed altered gene expression profiles. Autolysin-encoding genes such as sceD, a lytic transglycosylase encoding gene, were upregulated, like in vancomycin-intermediate S. aureus mutants (VISA). Genes related to cell wall-anchored proteins, secreted proteins, transporters, and toxins were downregulated. Overall, we demonstrate that bicarbonate deficiency is a stress response that causes changes in cell wall composition and global gene expression resulting in increased resilience to cell wall lytic enzymes and detergents. [ABSTRACT FROM AUTHOR]

This study proposes an affordable plasma device that utilizes a parallel-plate dielectric barrier discharge geometry with a metallic mesh electrode, featuring a straightforward 3D-printed design. Powered by a high-voltage supply adapted from a cosmetic plasma device, it operates on atmospheric air, eliminating the need for gas flux. Surface modification of polyethylene treated with this device was characterized and showed that the elemental composition after 15 min of plasma treatment decreased the amount of C to ~80 at% due to the insertion of O (~15 at%). Tested against Candida albicans and Staphylococcus aureus, the device achieved a reduction of over 99% in microbial load with exposure times ranging from 1 to 10 min. Simultaneously, the Vero cell viability remained consistently high, namely between 91% and 96% across exposure times. These results highlight this device's potential for the surface modification of materials and various infection-related applications, boasting affordability and facilitating effective antimicrobial interventions. [ABSTRACT FROM AUTHOR]

The cell wall is an indispensable element of bacterial cells and a long-known target of many antibiotics. Penicillin, the first discovered beta-lactam antibiotic inhibiting the synthesis of cell walls, was successfully used to cure many bacterial infections. Unfortunately, pathogens eventually developed resistance to it. This started an arms race, and while novel beta-lactams, either natural or (semi)synthetic, were discovered, soon upon their application, bacteria were developing resistance. Currently, we are facing the threat of losing the race since more and more multidrug-resistant (MDR) pathogens are emerging. Therefore, there is an urgent need for developing novel approaches to combat MDR bacteria. The cell wall is a reasonable candidate for a target as it differentiates not only bacterial and human cells but also has a specific composition unique to various groups of bacteria. This ensures the safety and specificity of novel antibacterial agents that target this structure. Due to the shortage of low-molecular-weight candidates for novel antibiotics, attention was focused on peptides and proteins that possess antibacterial activity. Here, we describe proteinaceous agents of various origins that target bacterial cell wall, including bacteriocins and phage and bacterial lysins, as alternatives to classic antibiotic candidates for antimicrobial drugs. Moreover, advancements in protein chemistry and engineering currently allow for the production of stable, specific, and effective drugs. Finally, we introduce the concept of selective targeting of dangerous pathogens, exemplified by staphylococci, by agents specifically disrupting their cell walls. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus possesses sar family genes, including sarA, S, R, T, U, V, X, Y, Z, and rot, which are transcription factors involved in biofilm formation and quorum sensing. In contrast, Staphylococcus epidermidis has sarA, R, V, X, Y, Z, and rot genes; specifically, SarA, Z, and X are involved in biofilm formation. The expression of the sar family members in S. epidermidis isolated from clinical and non-clinical environments is unknown. This study aimed to establish if clinical and non-clinical isolates of S. epidermidis express the sar family members. We genotyped isolates from clinical ocular infections (n = 52), or non-clinical healthy conjunctiva (n = 40), and healthy skin (n = 50), using multilocus sequence typing (MLST) and the staphylococcal chromosomal cassette mec (SCCmec). We selected strains with different genotypes and representatives of each source of isolation, and the presence of the sar family genes was detected using PCR and RT-qPCR to determine their expression. The sar family genes were present in all selected strains, with no observed differences. The relative expression of the sar family showed that all selected strains expressed each gene weakly, with no significant differences observed between them or between different sources of isolation. In conclusion, the presence and relative expression of the sar family genes are very similar among strains, with no differences based on their origin of isolation and genotype. [ABSTRACT FROM AUTHOR]

Asthma is a chronic respiratory disease that affects children worldwide. Increasing evidence suggests that Staphylococcus aureus contributes to the pathology of asthma. The aim of this study was to evaluate the nasal carriage, antimicrobial susceptibility profile, and presence of enterotoxin genes from S. aureus isolated from children with asthma. Nasal swab samples were collected from 158 children, including 98 children with asthma and 60 healthy controls. S. aureus isolates were identified using phenotypic methods and the presence of the nuc gene. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disc diffusion method. Polymerase chain reaction (PCR) confirmed the presence of the mecA gene and enterotoxin genes. The nuc gene was confirmed in 83 isolates, resulting in a nasal carriage of 52.5% (83/158). The nasal carriage of S. aureus was higher among asthma cases (72.4%), with a significant association of S. aureus nasal carriage observed among asthma cases (OR 0.201, 95% CI 0.063–0.645, p = 0.007). Methicillin-resistant S. aureus (MRSA) nasal carriage was 11.4%. The S. aureus isolates showed high resistance to cefoxitin (99%) and penicillin (92%) but were sensitive to gentamicin (25%). Furthermore, 67.5% of the isolates were multi-drug resistant. The staphylococcal enterotoxin c gene (sec) was the most prevalent enterotoxin (19.7%) among cases and controls. These findings highlight the need for improved antibiotic stewardship in paediatric medicine and implementation of infection control policies. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) is a highly infectious pathogen that poses a serious threat to human life and health. This study aimed to provide a scientific basis for the rational clinical use of antimicrobial drugs for treating MRSA infections and inform the development of preventive and control measures by analyzing the clinical distribution and resistance characteristics of MRSA in a hospital in Hebei China. To accomplish this, bacterial identification and drug sensitivity experiments were performed with 1858 Staphylococcus aureus (S. aureus) strains collected from a hospital from January 2018 to December 2022 using a phoenixTM-100 bacterial identification drug sensitivity analyzer. The experimental data were analyzed using WHONET 5.6 software, and the MRSA strains detected were analyzed for their clinical distribution and drug resistance. Of the 1858 S. aureus strains isolated, 429 were MRSA. Sputum samples had the highest MRSA detection rates (52.45%). Critical care medicine had the highest rate of MRSA (12.59%), followed by dermatology (9.79%). MRSA resistance to tetracycline increased by 13.9% over 5 years; resistance to quinupristin/dalfopristin also increased but remained low (1.9%). Resistance decreased to gentamicin, rifampicin, ciprofloxacin, and cotrimoxazole, though most significantly to erythromycin and clindamycin, exceeding 77% and 83%, respectively. No strains were resistant to vancomycin, teicoplanin, or linezolid, and drug resistance was most prevalent in patients ≥ 60 years old. This study will aid in improving the diagnosis and treatment of MRSA infections. [ABSTRACT FROM AUTHOR]

Simple Summary: This manuscript reports on an outbreak of joint infections in an organic broiler breeder flock in Austria, associated with two types of bacteria: Staphylococcus aureus and Staphylococcus lentus. The clinical picture of the affected chickens included weakness, lethargy, and difficulty walking, with some birds succumbing to the infection. Detailed examinations revealed severe joint inflammation and damage. Laboratory analyses confirmed the presence of both bacteria, with tests showing resistance to many antibiotics. This study underscores the importance of recognising and understanding less common bacteria like S. lentus, which are not frequently reported but can seriously impact poultry health. The findings highlight the need for thorough bacterial identification in outbreaks to improve disease management and prevention strategies. Staphylococcus species are widespread in poultry environments and can cause various infections, often when the host's defences are compromised. This manuscript reports on a co-infection of chickens with Staphylococcus lentus and Staphylococcus aureus associated with an outbreak of arthritis, synovitis, and osteomyelitis in an organic broiler breeder flock in Austria. Clinically, the affected flock showed weakness, lethargy, lameness, and increased mortality. Post-mortem examinations identified purulent arthritis and femoral head necrosis. Bacteriological analysis using MALDI-TOF MS identified both S. aureus and S. lentus in the affected joints. Antibiotic resistance testing revealed significant resistance, particularly in S. lentus. Histological analysis showed severe inflammation and bacterial colonies in the joints. While S. aureus is a common pathogen in poultry, S. lentus is less frequently reported. This study emphasises the need for detailed bacterial characterisation in outbreaks to better understand the role of less common pathogens like S. lentus. Further research is necessary to elucidate the impact of S. lentus on poultry health and its role in causing arthritis and synovitis, highlighting the importance of comprehensive investigation in such outbreaks. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus stands as a prominent cause for both nosocominal and community acquired infections across the globe. Clindamycin, a member of MLSB family, has emerged as the preferred choice for treating Staphylococcus aureus infections. However, one critical consideration in administering Clindamycin is the potential development of inducible Clindamycin resistance, posing a significant risk of clinical treatment failure. Aim: The study was aimed to determine the occurence of inducible Clindamycin resistance among Staphylococcus aureus isolates in our geographic region. Method: The hospital based cross sectional study was conducted over a period of one year from January 2023 to December 2023. A total of 672 Staphylococcus aureus isolates were identified by conventional methods and subjected to antimicrobial susceptibility test by Kirby Bauer disk diffusion method and Erythromycin resistant isolates were tested for D test. Result: Out of 672 Staphylococcus aureus isolates, 517 were MRSA and 155 were MSSA. Erythromycin resistance was seen in 395 (58.77%) isolates. D test revealed inducible clindamycin resistance in 45 (6.69%) isolates, constitutive clindamycin resistance in 91 (13.54%) isolates and MS phenotype in 259 (38.54%) isolates. Inducible clindamycin resistance was more in MRSA (7.73%) isolates compared to MSSA (3.22%) isolates. Conclusion: D test is a simple and cost-effective test that should be performed as routine laboratory test and will help in guiding the clinicians regarding judicious use of Clindamycin. [ABSTRACT FROM AUTHOR]