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The evolution of during the modern antibiotic era has been delineated by distinct strain emergence events, many of which include acquisition of antibiotic resistance. The relative high burden of methicillin-resistant (MRSA) in healthcare and community settings is a major concern worldwide. Vancomycin, a glycopeptide antibiotic that inhibits cell wall biosynthesis, remains a drug of choice for treatment of severe MRSA infections. strains exhibiting increased resistance to vancomycin, known as vancomycin intermediate-resistant (VISA) (MIC = 4-8 µg/mL), were discovered in the 1990s. The molecular basis of resistance in VISA is polygenic and involves stepwise mutations in genes encoding molecules predominantly involved in cell envelope biosynthesis. isolates with complete resistance to vancomycin (MIC ≥ 16 µg/mL) are termed vancomycin-resistant (VRSA)-they were first reported in the U.S. in 2002. Resistance in VRSA is conferred by the gene and operon, which is present on a plasmid. Although treatment of VRSA infections is challenging, the total number of human VRSA infections to date is limited (14 in the U.S.). By comparison, the burden of VISA is relatively high and the molecular mechanisms of resistance are less well-defined. VISA are associated with persistent infections, vancomycin treatment failure, and poor clinical outcomes. Here, we review in brief progress made toward understanding the acquisition of antibiotic resistance in , with an emphasis on the molecular mechanisms underlying vancomycin resistance.

The emergence of drug-resistant Staphylococcus aureus is responsible for high morbidity and mortality worldwide. New therapeutic options are needed to fight the increasing antimicrobial resistance among S. aureus in the clinical setting. We, therefore, characterized the in silico absorption, distribution, metabolism, elimination, and toxicity (ADMET) and in vitro antimicrobial activity of 5-nitro-2-thiophenecarbaldehyde N-((E)-(5-nitrothienyl)methylidene)hydrazone (KTU-286) against drug-resistant S. aureus strains with genetically defined resistance mechanisms. The antimicrobial activity of KTU-286 was determined by CLSI recommendations. The ADMET properties were estimated by using in silico modeling. The activity on biofilm integrity was examined by crystal violet assay. KTU-286 demonstrated low estimated toxicity and low skin permeability. The highest antimicrobial activity was observed among pan-susceptible (Pan-S) S. aureus (minimal inhibitory concentration (MIC) 0.5–2.0 µg/mL, IC50 = 0.460 µg/mL), followed by vancomycin resistant S. aureus (VRSA) (MIC 4.0 µg/mL, IC50 = 1.697 µg/mL) and methicillin-resistant S. aureus (MRSA) (MIC 1.0–16.0 µg/mL, IC50 = 2.282 µg/mL). KTU-286 resulted in significant (p < 0.05) loss of S. aureus biofilm integrity in vitro. Further studies are needed for a better understanding of safety, synergistic relationship, and therapeutic potency of KTU-286.

The emergence of pandrug-resistant (PDR) and extensive drug-resistant (XDR) methicillin-resistant and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA) isolates from bovine milk samples along with biofilm formation ability and harboring various virulence genes complicates the treatment of bovine mastitis and highlights the serious threat to public health. This study investigated for the first time the frequency, antimicrobial resistance profiles, biofilm-forming ability, virulence factors, spa and staphylococcal cassette chromosome mec (SCC mec ) types of MRSA and VRSA isolated from clinical and subclinical bovine mastitis in Egypt. A total of 808 milk samples were collected from each quarter of 202 dairy animals, including 31 buffaloes and 171 cattle. The frequency of mastitis in the collected milk samples was 48.4% (60/124) in buffaloes and 29.2% (200/684) in cattle. A total of 65 Staphylococcus species isolates were recovered, including 27 coagulase-positive S. aureus (CoPS) isolates and 38 coagulase-negative staphylococci (CoNS). The CoNS included 27 mammaliicocci (20 Mammaliicoccus lentus and 7 M. sciuri ) and 11 Non-aureus staphylococci ( S. lugdunensis ) isolates. All the CoPS isolates were mec A positive and resistant to 20–33 tested antimicrobials with multiple antibiotic resistance index ranging from 0.61 to 1. Three isolates were PDR, four were XDR, and 20 were multidrug resistant isolates. VRSA was detected in 85.2% of CoPS isolates with minimal inhibitory concentration (MIC) ranging from 64 to 1024 µg/mL. The van A gene was found in 60.8%, van B in 73.9%, and both genes in 43.5% of VRSA isolates. All the CoPS isolates exhibited biofilm formation ability, with 55.6% being strong, and 44.4% moderate biofilm producers, and harbored ica A (74.1%) and ica D (74.1%) biofilm-forming genes. All S. aureus isolates harbored both beta-haemolysin ( hlb ) and leucotoxin ( luk MF) genes, while 44.4% were positive for toxic shock syndrome toxin ( tsst ) gene. Enterotoxin genes sea , seb , sec , sed , and see were found in 59.3%, 40.7%, 18.5%, 33.3%, and 14.8% of isolates, respectively. Additionally, 70.4% of the isolates had  spa X-region gene, and exhibited eight different MRSA spa types (t127, t267, t037, t011, t843, t1081, t2663, and t1575), with spa t127 being the most common. Three SCC mec types (I, II and III) were identified, with SCC mec I being predominant, and were further classified into subtypes 1.1.1, 1.1.2, 1.n.1, and 4.1.1. The ability of MRSA and VRSA isolates to produce biofilms and resist antimicrobials highlights the serious threat these pathogens pose to bovine milk safety, animal welfare, and public health. Therefore, strict hygiene practices and antimicrobial surveillance are crucial to reduce the risk of MRSA and VRSA colonization and dissemination.

Vancomycin-resistant Staphylococcus aureus (VRSA) is a rare but serious public health concern. We describe a VRSA case in North Carolina, USA. The isolate from the case belonged to the USA600 lineage and clonal complex 45. No transmission was identified. Confirmed VRSA cases should include a thorough investigation and public health response.

The rise of biocide- and antibiotic-resistant microbes in hospital settings demands urgent and innovative strategies to curb the spread of antimicrobial resistance (AMR). This study presents an innovative disinfectant strategy that leverages antimicrobial peptides (APep) extracted from antimicrobial-producing (AMP) strains isolated from hospital environments under intense antibiotic pressure. Unlike traditional probiotic disinfectants that rely on live bacterial strains prone to AMR, this approach directly utilizes APep from non-resistant strains with a high antioxidant potential to combat AMR and oxidative stress. Candidate strains were selected based on antimicrobial susceptibility profiling, oxidative stress assays, and screening for antimicrobial activity against hospital-acquired pathogens. The active compounds were characterized using fourier-transform infrared (FTIR) spectroscopy, high-performance liquid chromatography (HPLC), liquid chromatography–tandem mass spectrometry (LC-MS/MS), and whole-genome sequencing. Biosynthetic pathways were explored using in silico analyses, including biosynthetic gene clusters (BGCs) mapping, APep prediction, and gene interaction network analyses. Bacillus paralicheniformis UAB33 was identified as a potent producer of bacitracin B1 (UB1), exhibiting strong activity against biocides and vancomycin-resistant Staphylococcus aureus (VRSA). Genomic analysis revealed 14 BGCs, including key non-ribosomal peptides (NRPs) such as bacitracin, lichenysin, and bacillibactin. A unique pathway involving bacA , bacB , and bacC genes, along with adjacent post-translationally modified peptides (RiPP) clusters, was elucidated to enhance bacitracin synthesis. UB1-infused disinfectant wipes significantly reduce microbial loads on hospital surfaces in vitro, demonstrating a promising strategy for mitigating resistant pathogens. This strategy presents a promising approach for curbing the spread of antibiotic resistance in healthcare settings and offers a scalable and innovative solution for infection control.

Background The emergence of vancomycin-resistant Staphylococcus aureus (VRSA) represents a challenge for the treatment of staphylococcal infections in both human and animals worldwide. Although VRSA has been detected in several animal species worldwide, data on the bacterial prevalence in dromedary camels and workers in camel slaughterhouses are scarce. Methods We investigated meat samples from 200 dromedary camel carcasses from three different abattoirs that were being prepared to be sent to the markets. Twenty hand swabs were voluntarily collected from the workers in the same abattoirs. Isolation and identification of the bacterial specimens from the samples were performed using conventional cultural techniques and biochemical identification and were confirmed by PCR amplification of the nuc gene. Antimicrobial susceptibility against nine antimicrobial agents commonly used in human and camels was tested using the disc diffusion method, and genetic analysis was performed by evaluating the mecA gene in phenotypically oxacillin (OXA)- and cefoxitin (FOX)-resistant isolates. The resistance of S. aureus to vancomycin (VAN) was tested by broth microdilution and confirmed by PCR targeting the vanA and vanB genes. The vanA and vanB genes were sequenced. Result S. aureus was detected in both camel meat (29/200, 14.5%) and in abattoir workers (11/20, 55%). Of the collected samples, 27% (8/29, camel) and 54% (6/11, human) were identified as VRSA. All VRSA isolates carried both the vanA and vanB genes. Additionally, all VRSA isolates were also classified as methicillin-resistant S. aureus (MRSA). The vanA amplicons of the isolates from human and camel meat were homologous and clustered with a Chinese reference isolate sequence. Conclusion This study demonstrated that VRSA is present in camel abattoirs in Egypt. Zoonotic transmission between animals and human is probable and reflects both a public health threat and a food safety concern.

Making use of a Diels–Alder approach based on various α,β-unsaturated 2-carbomethoxy-4,4-dimethyl-1-tetralones as novel dienophiles, the corresponding polycyclic adducts could be efficiently synthesized in good to high yields (74~99%) in the presence of Lewis acid (e.g., SnCl4). Accordingly, a synthetically useful platform is established to provide a focused aromatic polyketide-like library for screening of potential natural and non-natural antimicrobial agents.

Background Staphylococcus aureus strains are highly virulent and associated with an eclectic range of severe nosocomial and community-acquired infections. Objectives This study assessed methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA/VRSA) from clinical and ready-to-eat (RTE) food sources, screened for antibiotic resistance; and molecular determinants of antibiotic and virulence genes. Methods Altogether, 465 clinical and RTE food samples were analyzed via conventional microbiological techniques and S. aureus identification was confirmed by nuc gene detection. Phenotypic screening for methicillin and vancomycin-resistance was by agar-screen cum micro-broth dilution respectively, while antibiotic susceptibility testing was done by the disc-diffusion technique. VanA/vanB/VanC1 , femA , mecA/mecC; pvl/hlg and spa gene detection was via Polymerase chain reaction. Results Phenotypically, 211 Staphylococcal isolates were recovered, 138 (65.4%) of them carrying the nuc gene – all 138 (100.0%) were VRSA, while 59/138 (42.8%) were MRSA phenotypically. Overall, 114/138 (82.6%), 7/138 (5.1%), and 6/138 (4.3%) of isolates had the femA , mecA , and mecC genes, while van genes were detected in only 3 (2.2%) isolates, with virulence determinants pvl , hlg , and spa gene carriage in 8 (5.8%), 10 (7.2%), and 77 (55.8%) isolates respectively. In all, 11.6% carried resistance-associated genes, 55.8% carried virulence genes, and co-detection of resistance and virulence genes was observed in 12.3%. Overall, 96/138 (69.6%) were multidrug-resistant (MDR), while one strain was extremely drug-resistant (XDR). MAR Indices ≥ 0.2 was observed in 83.3% of isolates. Conclusion This study highlights virulence levels of MRSA and VRSA circulating strains in Osogbo, contributing to their sustained surveillance, and improving available data for successive epidemiology investigations. This study also reports the occurrence of the mecC gene in S. aureus isolates from RTE foods and human samples in Southwestern Nigeria.

Background Staphylococcus aureus clinical isolates with vancomycin MICs of 2 µg/ml have been associated with vancomycin therapeutic failure and the heterogenous vancomycin-intermediate S. aureus (hVISA) phenotype. While carriage of van genes has usually been associated with higher level of MIC and frank vancomycin resistance, the unrecognized risk of hetero-resistance is frequently underestimated. Methods used for assessing vancomycin susceptibility have also shown different concordance and variable performance and accessibility in routine clinical diagnostics posing a challenge to inform treatment selection in hospital settings. Methods A total of 195 clinical samples were obtained among which 100 S. aureus isolates were identified. Ninety-six MRSA isolates have been identified using cefoxitin disc and mec A gene detection. The van A and van B genes have been screened for in the studied isolates using conventional PCR amplification. Examination of reduced vancomycin susceptibility has been performed using vancomycin screen agar, Broth Micro Dilution method (BMD), and VITEK2. Blood isolates were screened for hVISA using PAP-AUC method. Results Vancomycin screening agar applied to 96 MRSA isolates revealed 16 isolates with reduced vancomycin susceptibility. Further MIC testing revealed that 7 isolates were VISA and only 1 isolate was identified as VRSA using both BMD MIC method and VITEK2. Among 24 tested blood isolates, 4 isolates (16.7%) revealed the hVISA phenotype as identified using PAP-AUC method. Using PCR, van A gene was identified in 5 S. aureus isolates (5%). Three of them were VSSA while the other two isolates were VISA. Conclusion In this study, we report the very low prevalence of VRSA among the tested S. aureus clinical isolates (1%) and the existence of hVISA phenotype among studied S. aureus blood isolates at the rate of 16.7% in our setting. Fifty percent (8/16) of isolates that demonstrated reduced vancomycin susceptibility using vancomycin agar screen tested susceptible using both broth dilution method and VITEK2. These finding together with the concerning silent carriage of van A gene among VSSA and VISA (5%) may underly hidden and uninvestigated factors contributing to vancomycin treatment failure that warrant cautious vancomycin prescription.

As a growing direction, nano-based therapy has become a successful paradigm used to address the phytogenic delivery-related problems in overcoming multivirulent vancomycin-resistant (VRSA) infection. Hence, our aim was to develop and assess a novel nanocarrier system (mesoporous silica nanoparticles, MPS-NPs) for free berberine (Free-BR) as an antimicrobial alkaloid against strong biofilm-producing and multi-virulent VRSA strains using and mouse model. Our outcomes demonstrated vancomycin resistance in 13.7% of ( ) strains categorized as VRSA. Notably, strong biofilm formation was observed in 69.2% of VRSA strains that were all positive for gene. All strong biofilm-producing VRSA strains harbored a minimum of two virulence genes comprising and with 44.4% of them possessing all five virulence genes ( , , , , and ), and 88.9% being multi-virulent. The study findings affirmed excellent antimicrobial and antibiofilm properties of BR-loaded MPS-NPs. Real-time quantitative reverse transcription PCR (qRT-PCR) assay displayed the downregulating role of BR-loaded MPS-NPs on strong biofilm-producing and multi-virulent VRSA strains virulence and genes in both and mice models. Additionally, BR-loaded MPS-NPs supplementation has a promising role in attenuating the upregulated expression of pro-inflammatory cytokines' genes in VRSA-infected mice with attenuation in pro-apoptotic genes expression resulting in reduced VRSA-induced apoptosis. In essence, the current study recommends the future scope of using BR-loaded MPS-NPs as auspicious alternatives for antimicrobials with tremendous antimicrobial, antibiofilm, anti-quorum sensing (QS), and anti-virulence effectiveness against problematic strong biofilm-producing and multi-virulent VRSA-associated infections.