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1. 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 pathophysiologymore »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.« less
2. 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)

   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.
3. Environmental Surveillance and Characterization of Antibiotic Resistant Staphylococcus aureus at Coastal Beaches and Rivers on the Island of Hawaiʻi

   https://doi.org/10.3390/antibiotics10080980  

   Gerken, Tyler J. ; Roberts, Marilyn C. ; Dykema, Philip ; Melly, Geoff ; Lucas, Darren ; De Los Santos, Vanessa ; Gonzalez, Joenice ; Butaye, Patrick ; Wiegner, Tracy N. ( August 2021 , Antibiotics)

   Staphylococcus aureus are human facultative pathogenic bacteria and can be found as contaminants in the environment. The aim of our study was to determine whether methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) isolated from coastal beach and river waters, anchialine pools, sand, and wastewater on the island of Hawaiʻi, Hawaiʻi, are a potential health risk. Samples were collected from three regions on Hawaiʻi Island from July to December 2020 during the COVID-19 pandemic and were characterized using whole-genome sequencing (WGS). From WGS data, multilocus sequence typing (MLST), SCCmec type, antimicrobial resistance genes, virulence factors, and plasmids were identified. Of the 361 samples, 98.1% were positive for Staphylococcus spp. and 7.2% were S. aureus positive (n = 26); nine MRSA and 27 MSSA strains were characterized; multiple isolates were chosen from the same sample in two sand and seven coastal beach water samples. The nine MRSA isolates were multi-drug resistant (6–9 genes) sequence type (ST) 8, clonal complex (CC) 8, SCCmec type IVa (USA300 clone), and were clonally related (0–16 SNP differences), and carried 16–19 virulence factors. The 27 MSSA isolates were grouped into eight CCs and 12 STs. Seventy-eight percent of the MSSA isolates carried 1–5 different antibioticmore »resistance genes and carried 5–19 virulence factors. We found S. aureus in coastal beach and river waters, anchialine pools, and sand at locations with limited human activity on the island of Hawaiʻi. This may be a public health hazard.« less
4. TAL Effectors with Avirulence Activity in African Strains of Xanthomonas oryzae pv. oryzae

   https://doi.org/10.1186/s12284-022-00553-9  

   Lachaux, Marlène ; Thomas, Emilie ; Bogdanove, Adam J. ; Szurek, Boris ; Hutin, Mathilde ( February 2022 , Rice)

   Xanthomonas oryzaepv.oryzae(Xoo) causes bacterial leaf blight, a devastating disease of rice. Among the type-3 effectors secreted byXooto support pathogen virulence, the Transcription Activator-Like Effector (TALE) family plays a critical role. Some TALEs are major virulence factors that activate susceptibility (S) genes, overexpression of which contributes to disease development. Host incompatibility can result from TALE-induced expression of so-called executor (E) genes leading to a strong and rapid resistance response that blocks disease development. In that context, the TALE functions as an avirulence (Avr) factor. To date no such avirulence factors have been identified in African strains ofXoo.

   With respect to the importance of TALEs in the Rice-Xoopathosystem, we aimed at identifying those that may act as Avr factor within AfricanXoo. We screened 86 rice accessions, and identified 12 that were resistant to two African strains while being susceptible to a well-studied Asian strain. In a gain of function approach based on the introduction of each of the ninetalgenes of the avirulent African strain MAI1 into the virulent Asian strain PXO99^A, four were found to trigger resistance on specific rice accessions. Loss-of-function mutational analysis further demonstrated theavractivity of two of them,talDandtalI,on the rice varieties IR64 and CT13432 respectively. Further analysis ofmore »TalI demonstrated the requirement of its activation domain for triggering resistance in CT13432. Resistance in 9 of the 12 rice accessions that were resistant against AfricanXoospecifically, including CT13432, could be suppressed or largely suppressed by trans-expression of the truncTALEtal2h, similarly to resistance conferred by theXa1gene which recognizes TALEs generally independently of their activation domain.

   We identified and characterized TalD and TalI as two AfricanXooTALEs with avirulence activity on IR64 and CT13432 respectively. Resistance of CT13432 against AfricanXooresults from the combination of two mechanisms, one relying on the TalI-mediated induction of an unknown executor gene and the other on anXa1-like gene or allele.

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5. Fusogenic porous silicon nanoparticles as a broad-spectrum immunotherapy against bacterial infections

   https://doi.org/10.1039/D0NH00624F  

   Kim, Byungji ; Yang, Qinglin ; Chan, Leslie W. ; Bhatia, Sangeeta N. ; Ruoslahti, Erkki ; Sailor, Michael J. ( April 2021 , Nanoscale Horizons)

   Bacterial infections are re-emerging as substantial threats to global health due to the limited selection of antibiotics that are capable of overcoming antibiotic-resistant strains. By deterring such mutations whilst minimizing the need to develop new pathogen-specific antibiotics, immunotherapy offers a broad-spectrum therapeutic solution against bacterial infections. In particular, pathology resulting from excessive immune response ( i.e. fibrosis, necrosis, exudation, breath impediment) contributes significantly to negative disease outcome. Herein, we present a nanoparticle that is targeted to activated macrophages and loaded with siRNA against the Irf5 gene. This formulation is able to induce >80% gene silencing in activated macrophages in vivo , and it inhibits the excessive inflammatory response, generating a significantly improved therapeutic outcome in mouse models of bacterial infection. The versatility of the approach is demonstrated using mice with antibiotic-resistant Gram-positive (methicillin-resistant Staphylococcus aureus ) and Gram-negative ( Pseudomonas aeruginosa ) muscle and lung infections, respectively. Effective depletion of the Irf5 gene in macrophages is found to significantly improve the therapeutic outcome of infected mice, regardless of the bacteria strain and type.