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1. Investigation of Plasmids Among Clinical Staphylococcus aureus and Staphylococcus haemolyticus Isolates From Egypt

   https://doi.org/10.3389/fmicb.2021.659116  

   Mores, Carine R.; Montelongo, Cesar; Putonti, Catherine; Wolfe, Alan J.; Abouelfetouh, Alaa (June 2021, Frontiers in Microbiology)

   null (Ed.)

   Staphylococci can cause a wide array of infections that can be life threatening. These infections become more deadly when the isolates are antibiotic resistant and thus harder to treat. Many resistance determinants are plasmid-mediated; however, staphylococcal plasmids have not yet been fully characterized. In particular, plasmids and their contributions to antibiotic resistance have not been investigated within the Arab states, where antibiotic use is not universally regulated. Here, we characterized the putative plasmid content among 56 Staphylococcus aureus and 10 Staphylococcus haemolyticus clinical isolates from Alexandria, Egypt. Putative plasmid sequences were detected in over half of our collection. In total, we identified 72 putative plasmid sequences in 27 S. aureus and 1 S. haemolyticus isolates. While these isolates typically carried one or two plasmids, we identified one isolate— S. aureus AA53—with 11 putative plasmids. The plasmid sequences most frequently encoded a Rep_1, RepL, or PriCT_1 type replication protein. As expected, antibiotic resistance genes were widespread among the identified plasmid sequences. Related plasmids were identified amongst our clinical isolates; homologous plasmids present in multiple isolates clustered into 11 groups based upon sequence similarity. Plasmids from the same cluster often shared antibiotic resistance genes, including blaZ , which is associated with β-lactam resistance. Our analyses suggest that plasmids are a key factor in the pathology and epidemiology of S. aureus in Egypt. A better characterization of plasmids and the role they contribute to the success of Staphylococci as pathogens will guide the design of effective control strategies to limit their spread. 

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2. Human Urine Alters Methicillin-Resistant Staphylococcus aureus Virulence and Transcriptome

   https://doi.org/10.1128/AEM.00744-21  

   Paudel, Santosh; Bagale, Kamal; Patel, Swapnil; Kooyers, Nicholas J.; Kulkarni, Ritwij (July 2021, Applied and Environmental Microbiology)

   Dozois, Charles M. (Ed.)

   ABSTRACT Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) is an emerging cause of hospital-associated urinary tract infections (UTI), especially in catheterized individuals. Despite being rare, MRSA UTI are prone to potentially life-threatening exacerbations such as bacteremia that can be refractory to routine antibiotic therapy. To delineate the molecular mechanisms governing MRSA urinary pathogenesis, we exposed three S. aureus clinical isolates, including two MRSA strains, to human urine for 2 h and analyzed virulence characteristics and changes in gene expression. The in vitro virulence assays showed that human urine rapidly alters adherence to human bladder epithelial cells and fibronectin, hemolysis of sheep red blood cells (RBCs), and surface hydrophobicity in a staphylococcal strain-specific manner. In addition, transcriptome sequencing (RNA-Seq) analysis of uropathogenic strain MRSA-1369 revealed that 2-h-long exposure to human urine alters MRSA transcriptome by modifying expression of genes encoding enzymes catalyzing metabolic pathways, virulence factors, and transcriptional regulators. In summary, our results provide important insights into how human urine specifically and rapidly alters MRSA physiology and facilitates MRSA survival in the nutrient-limiting and hostile urinary microenvironment. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is an uncommon cause of urinary tract infections (UTI) in the general population. However, it is important to understand MRSA pathophysiology in the urinary tract because isolation of MRSA in urine samples often precedes potentially life-threatening MRSA bacteremia. In this report, we describe how exposure to human urine alters MRSA global gene expression and virulence. We hypothesize that these alterations may aid MRSA in acclimating to the nutrient-limiting, immunologically hostile conditions within the urinary tract leading to MRSA UTI. 

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3. Staphylococcus aureus secretes immunomodulatory RNA and DNA via membrane vesicles

   https://doi.org/10.1038/s41598-020-75108-3  

   Rodriguez, Blanca V.; Kuehn, Meta J. (October 2020, Scientific Reports)

   Abstract Bacterial-derived RNA and DNA can function as ligands for intracellular receptor activation and induce downstream signaling to modulate the host response to bacterial infection. The mechanisms underlying the secretion of immunomodulatory RNA and DNA by pathogens such asStaphylococcus aureusand their delivery to intracellular host cell receptors are not well understood. Recently, extracellular membrane vesicle (MV) production has been proposed as a general secretion mechanism that could facilitate the delivery of functional bacterial nucleic acids into host cells.S. aureusproduce membrane-bound, spherical, nano-sized, MVs packaged with a select array of bioactive macromolecules and they have been shown to play important roles in bacterial virulence and in immune modulation through the transmission of biologic signals to host cells. Here we show thatS. aureussecretes RNA and DNA molecules that are mostly protected from degradation by their association with MVs. Importantly, we demonstrate that MVs can be delivered into cultured macrophage cells and subsequently stimulate a potent IFN-β response in recipient cells via activation of endosomal Toll-like receptors. These findings advance our understanding of the mechanisms by which bacterial nucleic acids traffic extracellularly to trigger the modulation of host immune responses. 

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4. Methicillin-Resistant Staphylococcus aureus (MRSA): Antibiotic-Resistance and the Biofilm Phenotype

   https://doi.org/10.1039/C9MD00044E  

   Craft, Kelly M.; Nguyen, Johny; Berg, Lawrence; Townsend, Steven (January 2019, MedChemComm)

   Staphylococcus aureus (S. aureus) is an asymptomatic colonizer of 30% of all human beings. While generally benign, antibiotic resistance contributes to the success of S. aureus as a human pathogen. Resistance is rapidly evolved through a wide portfolio of mechanisms including horizontal gene transfer and chromosomal mutation. In addition to traditional resistance mechanisms, a special feature of S. aureus pathogenesis is its ability to survive on both biotic and abiotic surfaces in the biofilm state. Due to this characteristic, S. aureus is a leading cause of human infection. Methicillin-resistant S. aureus (MRSA) in particular has emerged as a widespread cause of both community- and hospital-acquired infections. Currently, MRSA is responsible for 10-fold more infections than all multi-drug resistant (MDR) Gram-negative pathogens combined. Recently, MRSA was classified by the World Health Organization (WHO) as one of twelve priority pathogens that threaten human health. In this targeted mini-review, we discuss MRSA biofilm production, the relationship of biofilm production to antibiotic resistance, and front-line techniques to defeat the biofilm-resistance system. 

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5. Examination of Staphylococcus aureus Prophages Circulating in Egypt

   https://doi.org/10.3390/v13020337  

   Ene, Adriana; Miller-Ensminger, Taylor; Mores, Carine R.; Giannattasio-Ferraz, Silvia; Wolfe, Alan J.; Abouelfetouh, Alaa; Putonti, Catherine (February 2021, Viruses)

   null (Ed.)

   Staphylococcus aureus infections are of growing concern given the increased incidence of antibiotic resistant strains. Egypt, like several other countries, has seen alarming increases in methicillin-resistant S. aureus (MRSA) infections. This species can rapidly acquire genes associated with resistance, as well as virulence factors, through mobile genetic elements, including phages. Recently, we sequenced 56 S. aureus genomes from Alexandria Main University Hospital in Alexandria, Egypt, complementing 17 S. aureus genomes publicly available from other sites in Egypt. In the current study, we found that the majority (73.6%) of these strains contain intact prophages, including Biseptimaviruses, Phietaviruses, and Triaviruses. Further investigation of these prophages revealed evidence of horizontal exchange of the integrase for two of the prophages. These Egyptian S. aureus prophages are predicted to encode numerous virulence factors, including genes associated with immune evasion and toxins, including the Panton–Valentine leukocidin (PVL)-associated genes lukF-PV/lukS-PV. Thus, prophages are likely to be a major contributor to the virulence of S. aureus strains in circulation in Egypt. 

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