Implant-associated Staphylococcus aureus (S. aureus) osteomyelitis is a severe challenge in orthopedics. While antibiotic-loaded bone cement is a standardized therapeutic approach for S. aureus osteomyelitis, it falls short in eradicating Staphylococcus abscess communities (SACs) and bacteria within osteocyte-lacuna canalicular network (OLCN) and repairing bone defects. To address limitations, we developed a borosilicate bioactive glass (BSG) combined with ferroferric oxide (Fe3O4) magnetic scaffold to enhance antibacterial efficacy and bone repair capabilities. We conducted comprehensive assessments of the osteoinductive, immunomodulatory, antibacterial properties, and thermal response of this scaffold, with or without an alternating magnetic field (AMF). Utilizing a well-established implant-related S. aureus tibial infection rabbit model, we evaluated its antibacterial performance in vivo. RNA transcriptome sequencing demonstrated that BSG + 5%Fe3O4 enhanced the immune response to bacteria and promoted osteogenic differentiation and mineralization of MSCs. Notably, BSG + 5%Fe3O4 upregulated gene expression of NOD-like receptor and TNF pathway in MSCs, alongside increased the expression of osteogenic factors (RUNX2, ALP and OCN) in vitro. Flow cytometry on macrophage exhibited a polarization effect towards M2, accompanied by upregulation of anti-inflammatory genes (TGF-β1 and IL-1Ra) and downregulation of pro-inflammatory genes (IL-6 and IL-1β) among macrophages. In vivo CT imaging revealed the absence of osteolysis and periosteal response in rabbits treated with BSG + 5%Fe3O4 + AMF at 42 days. Histological analysis indicated complete controls of SACs and bacteria within OLCN by day 42, along with new bone formation, signifying effective control of S. aureus osteomyelitis. Further investigations will focus on the in vivo biosafety and biological mechanism of this scaffold within infectious microenvironment.

Staphylococcus aureus (Sa) and Acinetobacter baumannii (Ab) are frequently co-isolated from polymicrobial infections that are severe and refractory to therapy. Here, we apply a combination of wet-lab experiments and in silico modeling to unveil the intricate nature of the Ab/Sa interaction using both, representative laboratory strains and strains co-isolated from clinical samples. This comprehensive methodology allowed uncovering Sa\'s capability to exert a partial interference on Ab by the expression of phenol-soluble modulins. In addition, we observed a cross-feeding mechanism by which Sa supports the growth of Ab by providing acetoin as an alternative carbon source. This study is the first to dissect the Ab/Sa interaction dynamics wherein competitive and cooperative strategies can intertwine. Through our findings, we illuminate the ecological mechanisms supporting their coexistence in the context of polymicrobial infections. Our research not only enriches our understanding but also opens doors to potential therapeutic avenues in managing these challenging infections.

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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.

UNASSIGNED: Implants are widely used in the field of orthopedics and dental sciences. Titanium (TI) and its alloys have become the most widely used implant materials, but implant-associated infection remains a common and serious complication after implant surgery. In addition, titanium exhibits biological inertness, which prevents implants and bone tissue from binding strongly and may cause implants to loosen and fall out. Therefore, preventing implant infection and improving their bone induction ability are important goals.
UNASSIGNED: To study the antibacterial activity and bone induction ability of titanium-copper alloy implants coated with nanosilver/poly (lactic-co-glycolic acid) (NSPTICU) and provide a new approach for inhibiting implant-associated infection and promoting bone integration.
UNASSIGNED: We first examined the in vitro osteogenic ability of NSPTICU implants by studying the proliferation and differentiation of MC3T3-E1 cells. Furthermore, the ability of NSPTICU implants to induce osteogenic activity in SD rats was studied by micro-computed tomography (micro-CT), hematoxylin-eosin (HE) staining, masson staining, immunohistochemistry and van gieson (VG) staining. The antibacterial activity of NSPTICU in vitro was studied with gram-positive Staphylococcus aureus (Sa) and gram-negative Escherichia coli (E. coli) bacteria. Sa was used as the test bacterium, and the antibacterial ability of NSPTICU implanted in rats was studied by gross view specimen collection, bacterial colony counting, HE staining and Giemsa staining.
UNASSIGNED: Alizarin red staining, alkaline phosphatase (ALP) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis showed that NSPTICU promoted the osteogenic differentiation of MC3T3-E1 cells. The in vitro antimicrobial results showed that the NSPTICU implants exhibited better antibacterial properties. Animal experiments showed that NSPTICU can inhibit inflammation and promote the repair of bone defects.
UNASSIGNED: NSPTICU has excellent antibacterial and bone induction ability, and has broad application prospects in the treatment of bone defects related to orthopedics and dental sciences.

An international collection of Staphylococcus aureus of clonal complex (CC) 398 from diverse hosts spanning all continents and a 30 year-period is studied based on whole-genome sequencing (WGS) data. The collection consists of publicly available genomic data from 2994 strains and 134 recently sequenced Swiss methicillin-resistant S. aureus (MRSA) CC398 strains. A time-calibrated phylogeny reveals the presence of distinct phylogroups present in Asia, North and South America and Europe. European MRSA diverged from methicillin-susceptible S. aureus (MSSA) at the beginning of the 1950s. Two major European phylogroups (EP4 and EP5), which diverged approximately 1974, are the main drivers of MRSA CC398 spread in Europe. Within EP5, an emergent MRSA lineage spreading among the European horse population (EP5-Leq) diverged approximately 1996 from the pig lineage (EP5-Lpg), and also contains human-related strains. EP5-Leq is characterized by staphylococcal cassette chromosome mec (SCCmec) IVa and spa type t011 (CC398-IVa-t011), and EP5-Lpg by CC398-SCCmecVc-t011. The lineage-specific antibiotic resistance and virulence gene patterns are mostly mediated by the acquisition of mobile genetic elements like SCCmec, S. aureus Genomic Islands (SaGIs), prophages and transposons. Different combinations of virulence factors are present on S. aureus pathogenicity islands (SaPIs), and novel antimicrobial resistance gene containing elements are associated with certain lineages expanding in Europe. This WGS-based analysis reveals the actual evolutionary trajectory and epidemiological trend of the international MRSA CC398 population considering host, temporal, geographical and molecular factors. It provides a baseline for global WGS-based One-Health studies of adaptive evolution of MRSA CC398 as well as for local outbreak investigations.

Plants are valuable resources for drug discovery as they produce diverse bioactive compounds. However, the chemical diversity makes it difficult to predict the biological activity of plant extracts via conventional chemometric methods. In this research, we propose a new computational model that integrates chemical composition data with structure-based chemical ontology. For a model validation, two training datasets were prepared from literature on antibacterial essential oils to classify active/inactive oils. Random forest classifiers constructed from the data showed improved prediction performance in both test datasets. Prior feature selection using hierarchical information criterion further improved the performance. Furthermore, an antibacterial assay using a standard strain of Staphylococcus aureus revealed that the classifier correctly predicted the activity of commercially available oils with an accuracy of 83% (= 10/12). The results of this study indicate that machine learning of chemical composition data integrated with chemical ontology can be a highly efficient approach for exploring bioactive plant extracts.

Patients with chronic limb-threatening ischaemia (CLTI) are at risk of foot infections, which is associated with an increase in amputation rates. The use of antibiotics may lead to a higher incidence of antimicrobial resistance (AMR) in subsequent episodes of ischaemic foot infections (IFI). This retrospective single-centre cohort study included 130 patients with IFI undergoing endovascular revascularisation. Staphylococcus aureus and Pseudomonas aeruginosa were the two most common pathogens, accounting for 20.5% and 10.8% of cases, respectively. The prevalence of antimicrobial resistance (AMR) and multi-drug resistance did not significantly increase between episodes (10.2% vs. 13.4%, p = 0.42). In 59% of subsequent episodes, the identified pathogens were unrelated to the previous episode. However, the partial concordance of identified pathogens significantly increased to 66.7% when S. aureus was identified (p = 0.027). Subsequent episodes of IFI in the same patient are likely to differ in causative pathogens. However, in the case of S. aureus, the risk of reinfection, particularly with S. aureus, is increased. Multi-drug resistance does not appear to change between IFI episodes. Therefore, recommendations for empirical antimicrobial therapy should be based on local pathogen and resistance statistics without the need to broaden the spectrum of antibiotics in subsequent episodes.

Broad-spectrum antibacterial drugs often lack specificity, leading to indiscriminate bactericidal activity, which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during systemic administration. In this study, we constructed a specifically targeted antimicrobial peptide against Staphylococcus aureus by introducing a phage-displayed peptide onto a broad-spectrum antimicrobial peptide and explored its structure-function relationship through one-factor modification. SFK2 obtained by screening based on the selectivity index and the targeting index showed specific killing ability against S. aureus. Moreover, SFK2 showed excellent biocompatibility in mice and piglet, and demonstrated significant therapeutic efficacy against S. aureus infection. In conclusion, our screening of phage-derived heptapeptides effectively enhances the specific bactericidal ability of the antimicrobial peptides against S. aureus, providing a theoretical basis for developing targeted antimicrobial peptides.

UNASSIGNED: Accurate identification of the etiology of orthopedic infection is very important for correct and timely clinical management, but it has been poorly studied. In the current study we explored the association of multiple bacterial pathogens with orthopedic infection.
UNASSIGNED: Hospitalized orthopedic patients were enrolled in a rural hospital in Qingdao, China. Wound or exudate swab samples were collected and tested for twelve bacterial pathogens with both culture and multiplex real time PCR.
UNASSIGNED: A total of 349 hospitalized orthopedic patients were enrolled including 193 cases presenting infection manifestations upon admission and 156 with no sign of infection. Orthopedic infection patients were mainly male (72.5%) with more lengthy hospital stay (median 15 days). At least one pathogen was detected in 42.5% (82/193) of patients with infection while 7.1% (11/156) in the patients without infection (P < 0.001). S. aureus was the most prevalent causative pathogen (15.5%). Quantity dependent pathogen association with infection was observed, particularly for P. aeruginosa and K. pneumoniae, possibly indicating subclinical infection. Most of the patients with detected pathogens had a previous history of orthopedic surgery (odds ratio 2.8, P = 0.038). Pathogen specific clinical manifestations were characterized. Multiplex qPCR, because of its high sensitivity, superior specificity, and powerful quantification could be utilized in combination with culture to guide antimicrobial therapy and track the progression of orthopedic infection during treatment.