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Staphylococcus aureus or methicillin-resistant Staphylococcus aureus (MRSA) is an important issue associated with significant morbidity and mortality and well known as a predominant pathogen causing bloodstream infection (BSIs) globally. To estimate the antibiotic resistance and molecular characteristics of S. aureus causing BSIs in Shanghai, 120  S. aureus isolates (20 isolates each year) from the patients with S. aureus BSIs from 2013 to 2018 were randomly selected and enrolled in this study. Fifty-three (44.2%) MRSA isolates were determined, and no isolate was found resistant to vancomycin, daptomycin, synercid, linezolid and ceftaroline. The toxin genes tst , sec , seg and sei were found more frequently among MRSA isolates compared with MSSA isolates (all P  < 0.0001). Twenty-nine sequence types (STs) were identified, and ST5 (23.3%) was the most common ST, followed by ST398 (11.7%) and ST764 (10.0%). SCC mec II (73.6%) was the most frequent SCC mec type among MRSA isolates. The dominant clonal complexes (CCs) were CC5 (ST5, ST764, ST965 and ST3066; 36.7%) and the livestock-associated clone CC398 (ST398, 11.7%). MRSA-CC5 was the predominant CC among MRSA isolates (37/53, 69.8%), and CC5-II MRSA was found in 34 isolates accounting for 91.9% (34/37) among CC5 MRSA isolates. In addition, all 29 tst -positive MRSA isolates were CC5-MRSA as well. Our study provided the properties and genotypes of S. aureus causing BSIs at Ruijin Hospital in Shanghai from 2013 to 2018, and might suggest of value clues for the further study insights into pathogenic mechanisms intrinsically referring to the development of human-adapted S. aureus clones and their diffusions.

Methicillin-Resistant Staphylococcus aureus (MRSA) is a significant threat to human health. Additionally, biofilm forming bacteria becomes more tolerant to antibiotics and act as bacterial reservoir leading to chronic infection. In this study, we characterised the antibiotic susceptibility, biofilm production and sequence types (ST) of 74 randomly selected clinical isolates of S. aureus causing ocular infections. Antibiotic susceptibility revealed 74% of the isolates as resistant against one or two antibiotics, followed by 16% multidrug-resistant isolates (MDR), and 10% sensitive. The isolates were characterized as MRSA (n = 15), Methicillin-sensitive S. aureus (MSSA, n = 48) and oxacillin susceptible mecA positive S. aureus (OS-MRSA, n = 11) based on oxacillin susceptibility, mecA gene PCR and PBP2a agglutination test. All OS-MRSA would have been misclassified as MSSA on the basis of susceptibility test. Therefore, both phenotypic and genotypic tests should be included to prevent strain misrepresentation. In addition, in-depth studies for understanding the emerging OS-MRSA phenotype is required. The role of fem XAB gene family has been earlier reported in OS-MRSA phenotype. Sequence analysis of the fem XAB genes revealed mutations in fem  × (K3R, H11N, N18H and I51V) and fem B (L410F) genes. The fem XAB genes were also found down-regulated in OS-MRSA isolates in comparison to MRSA. In OS-MRSA isolates, biofilm formation is regulated by fibronectin binding proteins A & B. Molecular typing of the isolates revealed genetic diversity. All the isolates produced biofilm, however, MRSA isolates with strong biofilm phenotype represent a worrisome situation and may even result in treatment failure.

Difficult-to-treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are of concern in people living with HIV infection as they are more vulnerable to infection. We aimed to identify molecular characteristics of MRSA colonizing newly diagnosed HIV-infected adults in Tanzania. Individuals newly diagnosed with HIV infection were recruited in Dar es Salaam, Tanzania, from April 2017 to May 2018, as part of the randomized clinical trial CoTrimResist (ClinicalTrials.gov identifier: NCT03087890). Nasal/nasopharyngeal isolates of Staphylococcus aureus were susceptibility tested by disk diffusion method, and cefoxitin-resistant isolates were characterized by short-reads whole genome sequencing. Four percent (22/537) of patients carried MRSA in the nose/nasopharynx. MRSA isolates were frequently resistant towards gentamicin (95%), ciprofloxacin (91%), and erythromycin (82%) but less often towards trimethoprim-sulfamethoxazole (9%). Seventy-three percent had inducible clindamycin resistance. Erythromycin-resistant isolates harbored ermC (15/18) and LmrS (3/18) resistance genes. Ciprofloxacin resistance was mediated by mutations of the quinolone resistance-determining region (QRDR) sequence in the gyrA (S84L) and parC (S80Y) genes. All isolates belonged to the CC8 and ST8-SCCmecIV MRSA clone. Ninety-five percent of the MRSA isolates were spa-type t1476, and one exhibited spa-type t064. All isolates were negative for Panton-Valentine leucocidin (PVL) and arginine catabolic mobile element (ACME) type 1. All ST8-SCCmecIV-spa-t1476 MRSA clones from Tanzania were unrelated to the globally successful USA300 clone. Carriage of ST8 MRSA (non-USA300) was common among newly diagnosed HIV-infected adults in Tanzania. Frequent co-resistance to non-beta lactam antibiotics limits therapeutic options when infection occurs.

Synthetic retinoid compounds can kill both growing and persister MRSA cells by disrupting the membrane lipid bilayer, and are effective in a mouse model of chronic MRSA infection. Drugs to beat persistence Bacterial persisters are a subpopulation of cells that can survive lethal antibiotics and other stresses. They are a major challenge for antimicrobial therapy as they cannot be killed by traditional therapeutic agents. Eleftherios Mylonakis and colleagues have developed retinoid compounds that can kill both growing and persister MRSA cells by disrupting the membrane. They develop one of these compounds with an improved cytotoxicity profile, and show that it is effective in treating a mouse model of chronic MRSA infection. Further development of these antibiotics is required to improve safety margins to move the antibiotics closer to being viable clinical candidates. A challenge in the treatment of Staphylococcus aureus infections is the high prevalence of methicillin-resistant S. aureus (MRSA) strains and the formation of non-growing, dormant ‘persister’ subpopulations that exhibit high levels of tolerance to antibiotics 1 , 2 , 3 and have a role in chronic or recurrent infections 4 , 5 . As conventional antibiotics are not effective in the treatment of infections caused by such bacteria, novel antibacterial therapeutics are urgently required. Here we used a Caenorhabditis elegans –MRSA infection screen 6 to identify two synthetic retinoids, CD437 and CD1530, which kill both growing and persister MRSA cells by disrupting lipid bilayers. CD437 and CD1530 exhibit high killing rates, synergism with gentamicin, and a low probability of resistance selection. All-atom molecular dynamics simulations demonstrated that the ability of retinoids to penetrate and embed in lipid bilayers correlates with their bactericidal ability. An analogue of CD437 was found to retain anti-persister activity and show an improved cytotoxicity profile. Both CD437 and this analogue, alone or in combination with gentamicin, exhibit considerable efficacy in a mouse model of chronic MRSA infection. With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure.

Secretion of extracellular vesicles (EVs), a process common to eukaryotes, archae, and bacteria, represents a secretory pathway that allows cell-free intercellular communication. Microbial EVs package diverse proteins and influence the host-pathogen interaction, but the mechanisms underlying EV production in Gram-positive bacteria are poorly understood. Here we show that EVs purified from community-associated methicillin-resistant Staphylococcus aureus package cytosolic, surface, and secreted proteins, including cytolysins. Staphylococcal alpha-type phenol-soluble modulins promote EV biogenesis by disrupting the cytoplasmic membrane; whereas, peptidoglycan cross-linking and autolysin activity modulate EV production by altering the permeability of the cell wall. We demonstrate that EVs purified from a S. aureus mutant that is genetically engineered to express detoxified cytolysins are immunogenic in mice, elicit cytolysin-neutralizing antibodies, and protect the animals in a lethal sepsis model. Our study reveals mechanisms underlying S. aureus EV production and highlights the usefulness of EVs as a S. aureus vaccine platform. Extracellular vesicles (EVs) influence host-pathogen interactions, but EV biogenesis in gram-positive bacteria remains elusive. Here authors characterize EVs from Staphylococcus aureus and show that phenol-soluble modulins and autolysins promote EV biogenesis by disrupting the membrane and cell wall.

This review assessed the molecular characterization of the methicillin-resistant Staphylococcus aureus (MRSA)-ST80 clone with an emphasis on its proportion of total MRSA strains isolated, PVL production, spa-typing, antibiotic resistance, and virulence. A systematic review of the literature was conducted on MRSA-ST80 clone published between 1 January 2000 and 31 August 2019. Citations were chosen for a review of the full text if we found evidence that MRSA-ST80 clone was reported in the study. For each isolate, the country of isolation, the sampling period, the source of isolation (the type of infection, nasal swabs, or extra-human), the total number of MRSA strains isolated, number of MRSA-ST80 strains, antibiotic resistance patterns, PVL production, virulence genes, and spa type were recorded. The data from 103 articles were abstracted into an Excel database. Analysis of the data showed that the overall proportion of MRSA-ST80 has been decreasing in many countries in recent years. The majority of MRSA-ST80 were PVL positive with spa-type t044. Only six reports of MRSA-ST80 in extra-human niches were found. This review summarizes the rise of MRSA-ST80 and the evidence that suggests that it could be in decline in many countries.

Background: The incidence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections is increasing in the United States, and it is possible that municipal wastewater could be a reservoir of this microorganism. To date, no U.S. studies have evaluated the occurrence of MRSA in wastewater. Objective: We examined the occurrence of MRSA and methicillin-susceptible S. aureus (MSSA) at U.S. wastewater treatment plants. Methods: We collected wastewater samples from two Mid-Atlantic and two Midwest wastewater treatment plants between October 2009 and October 2010. Samples were analyzed for MRSA and MSSA using membrane filtration. Isolates were confirmed using biochemical tests and PCR (polymerase chain reaction). Antimicrobial susceptibility testing was performed by Sensititre® microbroth dilution. Staphylococcal cassette chromosome mec (SCCmec) typing, Panton-Valentine leucocidin (PVL) screening, and pulsed field gel electrophoresis (PFGE) were performed to further characterize the strains. Data were analyzed by two-sample proportion tests and analysis of variance. Results: We detected MRSA (n = 240) and MSSA (n = 119) in 22 of 44 (50%) and 24 of 44 (55%) wastewater samples, respectively. The odds of samples being MRSA-positive decreased as treatment progressed: 10 of 12 (83%) influent samples were MRSA-positive, while only one of 12 (8%) effluent samples was MRSA-positive. Ninety-three percent and 29% of unique MRSA and MSSA isolates, respectively, were multidrug resistant. SCCmec types II and IV, the pvl gene, and USA types 100, 300, and 700 (PFGE strain types commonly found in the United States) were identified among the MRSA isolates. Conclusions: Our findings raise potential public health concerns for wastewater treatment plant workers and individuals exposed to reclaimed wastewater. Because of increasing use of reclaimed wastewater, further study is needed to evaluate the risk of exposure to antibiotic-resistant bacteria in treated wastewater.

The horizontal transmission of methicillin resistance to Staphylococcus aureus (MRSA) in hospital and community settings, and growing prevalence of these strains, presents a significant clinical challenge to the management of serious infections worldwide. While infection control initiatives have stemmed the rising prevalence, MRSA remains a significant pathogen. More recently, evidence that MRSA is becoming resistant to glycopeptides and newer therapies raises concern about the use of these therapies in clinical practice. Vancomycin resistance has become evident in select clinical settings through rising MICs, growing awareness of heteroresistance, and emergence of intermediate-resistant and fully resistant strains. While resistance to linezolid and daptomycin remains low overall, point mutations leading to resistance have been described for linezolid, and horizontal transmission of cfr-mediated resistance to linezolid has been reported in clinical isolates. These resistance trends for newer therapies highlight the ongoing need for new and more potent antimicrobial therapies.

Since its initial description in the 1960s, methicillin-resistant Staphylococcus aureus (MRSA) has developed multiple mechanisms for antimicrobial resistance and evading the immune system, including biofilm production. MRSA is now a widespread pathogen, causing a spectrum of infections ranging from superficial skin issues to severe conditions like osteoarticular infections and endocarditis, leading to high morbidity and mortality. Biofilm production is a key aspect of MRSA’s ability to invade, spread, and resist antimicrobial treatments. Environmental factors, such as suboptimal antibiotics, pH, temperature, and tissue oxygen levels, enhance biofilm formation. Biofilms are intricate bacterial structures with dense organisms embedded in polysaccharides, promoting their resilience. The process involves stages of attachment, expansion, maturation, and eventually disassembly or dispersion. MRSA’s biofilm formation has a complex molecular foundation, involving genes like icaADBC, fnbA, fnbB, clfA, clfB, atl, agr, sarA, sarZ, sigB, sarX, psm, icaR, and srtA. Recognizing pivotal genes for biofilm formation has led to potential therapeutic strategies targeting elemental and enzymatic properties to combat MRSA biofilms. This review provides a practical approach for healthcare practitioners, addressing biofilm pathogenesis, disease spectrum, and management guidelines, including advances in treatment. Effective management involves appropriate antimicrobial therapy, surgical interventions, foreign body removal, and robust infection control practices to curtail spread within healthcare environments.

Background This multicentre study investigated the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates across Xinjiang, China. We aimed to characterise resistance phenotypes, genotype distributions, virulence gene profiles, and regional variations to inform precise prevention strategies and clinical treatment of MRSA infections in Xinjiang. Methods MRSA clinical isolates (122) were collected from hospitals in Urumqi, Alaer, Tumxuk, and Yining cities. Following identification by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and mecA gene PCR confirmation, isolates underwent molecular characterisation using multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCC mec ) typing, and staphylococcal protein A ( spa ) typing. Antimicrobial susceptibility testing was conducted to evaluate resistance phenotypes according to the 2023 guidelines of the Clinical and Laboratory Standards Institute (CLSI). PCR was used to detect 16 resistance genes and 13 virulence genes. Results Among 122 MRSA isolates, significant regional variations were observed in the prevalence of resistance ( ermC , tetK , tetM , aac(6’)-aph(2’’) , and aph(3’)-III ) and virulence ( seb , sdrC , cap5H , and cap8H ) genes ( P  < 0.05). Molecular typing revealed that CC59-ST59 (52.46%) and CC22-ST22 (18.03%) were the predominant clonal groups in Xinjiang. ST59 was dominant in Urumqi (63.27%) and Alaer (61.29%), whereas ST22 prevailed in Yining (37.50%) and Tumxuk (34.62%). All isolates were resistant to penicillin and oxacillin. Fluoroquinolone resistance (22.45%–34.62%) was higher in Urumqi and Tumxuk, whereas tetracycline resistance (45.16%) was elevated in Alaer. Notably, ST22 clones from Xinjiang displayed unique spa types (t223 and t005), which were distinct from those in other Chinese regions. A Tumxuk-specific ST22-t005-IV clone exhibited multidrug resistance (ten antibiotic classes) and high virulence (100% carrying pvl , tsst-1 , and four other virulence genes). Conclusion MRSA epidemic strains in Xinjiang exhibit significant regional heterogeneity in molecular typing, resistance, and virulence profiles. Attention should be paid to the drug resistance of MRSA in different regions, while enhanced clinical surveillance is warranted for the unique spa type evolution within the ST22 lineage, particularly the highly virulent and multidrug-resistant ST22-t005-IV clone.