Granulocytic myeloid-derived suppressor cell activity during biofilm infection is regulated by a glycolysis/HIF1a axis DOI Creative Commons
Christopher M. Horn,

Prabhakar Arumugam,

Zachary Van Roy

и другие.

Journal of Clinical Investigation, Год журнала: 2024, Номер 134(8)

Опубликована: Фев. 29, 2024

Staphylococcus aureus is a leading cause of biofilm-associated prosthetic joint infection (PJI). A primary contributor to chronicity an expansion granulocytic myeloid-derived suppressor cells (G-MDSCs) that are critical for orchestrating the anti-inflammatory biofilm milieu. Single-cell sequencing and bioinformatic metabolic algorithms were used explore link between G-MDSC metabolism S. PJI outcome. Glycolysis hypoxia response through hypoxia-inducible factor-1 alpha (HIF-1a) significantly enriched in G-MDSCs. Interfering with both pathways vivo, using 2-deoxyglucose nanopreparation granulocyte-targeted HIF-1a conditional knockout mice, respectively, attenuated G-MDSC-mediated immunosuppression reduced bacterial burden mouse model PJI. In addition, scRNA-seq analysis granulocytes from patients also showed enrichment glycolysis genes. These findings support importance glycolysis/HIF-1a axis promoting activity persistence during

Язык: Английский

Progress of stimulus responsive nanosystems for targeting treatment of bacterial infectious diseases DOI
Niuniu Yang,

Mengyuan Sun,

Huixin Wang

и другие.

Advances in Colloid and Interface Science, Год журнала: 2024, Номер 324, С. 103078 - 103078

Опубликована: Янв. 5, 2024

Язык: Английский

Процитировано

19

Staphylococcus aureus Proteins Implicated in the Reduced Virulence of sarA and sarA/agr Mutants in Osteomyelitis DOI Creative Commons
Karen E. Beenken, Mara J. Campbell, Stephanie D. Byrum

и другие.

Microorganisms, Год журнала: 2025, Номер 13(1), С. 181 - 181

Опубликована: Янв. 16, 2025

Using a murine osteomyelitis model, we recently demonstrated that Staphylococcus aureus sarA and sarA/agr mutants generated in the USA300 strain LAC are attenuated to greater extent than an isogenic agr mutant this can be attributed significant increased production of extracellular proteases both mutants. Based on this, used mass-based proteomics approach compare proteomes LAC, its agr, sarA, mutants, derivatives all four these strains unable produce aureolysin, SspA, SspB, ScpA, or SplA-F. This allowed us identify proteins were present reduced amounts owing proteases. A total 1039 detected conditioned media (CM) from overnight cultures protease-mediated degradation was shown contribute abundance 224 (21.6%) CM Among specific previously implicated pathogenesis therapeutic recalcitrance S. osteomyelitis. demonstrates ability limit protease plays key role post-translational remodeling proteome degree correlated with virulence our it does so irrespective functional status agr. also suggests at least some may viable targets for prophylactic intervention.

Язык: Английский

Процитировано

2

Molecular reprogramming and phenotype switching in Staphylococcus aureus lead to high antibiotic persistence and affect therapy success DOI Open Access
Markus Huemer, Srikanth Mairpady Shambat, Judith Bergadà-Pijuan

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2021, Номер 118(7)

Опубликована: Фев. 11, 2021

Staphylococcus aureus causes invasive infections and easily acquires antibiotic resistance. Even antibiotic-susceptible S. can survive therapy persist, requiring prolonged treatment surgical interventions. These so-called persisters display an arrested-growth phenotype, tolerate high concentrations, are associated with chronic recurrent infections. To characterize these persisters, we assessed recovered directly from a patient suffering persistent infection. We show that host-mediated stress, including acidic pH, abscess environment, exposure promoted persister formation in vitro vivo. Multiomics analysis identified molecular changes response to acid stress leading overall virulent population. However, further of persister-enriched population revealed major reprogramming down-regulation virulence cell division up-regulation ribosomal proteins, nucleotide-, amino acid-metabolic pathways, suggesting their requirement fuel maintain the phenotype highlighting not completely metabolically inactive. Additionally, decreased aconitase activity ATP levels accumulation insoluble proteins involved transcription, translation, energy production correlated persistence aureus, underpinning mechanisms drive phenotype. Upon regrowth, regained potential active reduction exhibiting reversible state, crucial for targeted antipersister combination using retinoid derivatives antibiotics significantly reduced lag-phase heterogeneity murine infection model. Our results provide insights into help explain why so difficult treat.

Язык: Английский

Процитировано

84

Galleria mellonella as an infection model: an in-depth look at why it works and practical considerations for successful application DOI Open Access
Monalessa Fábia Pereira, Ciro César Rossi, Giarlã Cunha da Silva

и другие.

Pathogens and Disease, Год журнала: 2020, Номер 78(8)

Опубликована: Сен. 18, 2020

ABSTRACT The larva of the greater wax moth Galleria mellonella is an increasingly popular model for assessing virulence bacterial pathogens and effectiveness antimicrobial agents. In this review, we discuss details components G. larval immune system that underpin its use as alternative infection model, provide updated overview state art research with models to study virulence, in evaluation efficacy. Emphasis given studies relevant human veterinary pathogens, especially Escherichia coli bacteria ESKAPE group. addition, make practical recommendations rearing testing, overcoming potential limitations which facilitate intra- interlaboratory reproducibility.

Язык: Английский

Процитировано

81

Staphylococcus aureus in Agriculture: Lessons in Evolution from a Multispecies Pathogen DOI
So-Youn Park, Jennifer Ronholm

Clinical Microbiology Reviews, Год журнала: 2021, Номер 34(2)

Опубликована: Фев. 2, 2021

Staphylococcus aureus is a formidable bacterial pathogen that responsible for infections in humans and various species of wild, companion, agricultural animals. The ability S. to move between livestock due specific characteristics this bacterium as well modern practices.

Язык: Английский

Процитировано

63

B and T cell epitope-based peptides predicted from clumping factor protein of Staphylococcus aureus as vaccine targets DOI
Jyotirmayee Dey, Soumya Ranjan Mahapatra, Pratima Singh

и другие.

Microbial Pathogenesis, Год журнала: 2021, Номер 160, С. 105171 - 105171

Опубликована: Сен. 2, 2021

Язык: Английский

Процитировано

62

Cytokine-Mediated Crosstalk Between Keratinocytes and T Cells in Atopic Dermatitis DOI Creative Commons

Mélanie Humeau,

Katia Boniface, Charles Bodet

и другие.

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Апрель 7, 2022

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by barrier dysfunction, dysregulated immune response, and dysbiosis with increased Staphylococcus aureus colonization. Infiltration of various T helper cell subsets into lesional subsequent cytokine release are hallmark AD. Release cytokines both cells keratinocytes plays key role in inflammation drives many AD features. This review aims to discuss cytokine-mediated crosstalk between pathogenesis the potential impact virulence factors produced on these interactions.

Язык: Английский

Процитировано

42

Prevalence and Characterization of PVL-Positive Staphylococcus aureus Isolated from Raw Cow’s Milk DOI Creative Commons
Asmaa Sadat,

Radwa Reda Shata,

Alshimaa Farag

и другие.

Toxins, Год журнала: 2022, Номер 14(2), С. 97 - 97

Опубликована: Янв. 25, 2022

The present study aimed to investigate the prevalence, antibiotic susceptibility profiles, and some toxin genes of Panton-Valentine leukocidin (PVL)-positive Staphylococcus aureus (S. aureus) in unpasteurized raw cow's milk collected from retail outlets located at Mansoura, Dakahliya governorate, Egypt. In that context, a total 700 samples were investigated for presence S. aureus, which was identified 41.1% (288/700) samples. Among isolates, 113 PVL-positive subjected further analysis. existence toxin-related genes, including hemolysin (hla), toxic shock syndrome toxin-1 (tst), enterotoxins (sea, seb, sec, see, seg, sei, selj). Genotypic resistance strains performed detection blaZ mecA genes. sea, sec detected 44.2, 6.2%, 0.9%, respectively, while hla tst 54.9% respectively. successfully 84.9 (96/113) 32.7% (37/113) evaluated displayed high level penicillin, ampicillin, trimethoprim-sulfamethoxazole. Multidrug (resistant ≥3 antimicrobial classes) by all methicillin-resistant (MRSA) 38.2% methicillin-sensitive (MSSA) isolates. obtained findings are raising alarm virulent MRSA clones Egypt, suggesting requirement limiting use β-lactam drugs food-producing animals importance implementing strong hygiene procedures dairy farms processing plants.

Язык: Английский

Процитировано

41

Molecular Characteristics and Pathogenicity of Staphylococcus aureus Exotoxins DOI Open Access
Zhihao Zhu,

Hu Zuo,

Shaowen Li

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 25(1), С. 395 - 395

Опубликована: Дек. 28, 2023

Staphylococcus aureus stands as one of the most pervasive pathogens given its morbidity and mortality worldwide due to roles an infectious agent that causes a wide variety diseases ranging from moderately severe skin infections fatal pneumonia sepsis. S. produces exotoxins serve important virulence factors in aureus-related food poisoning both humans animals. For example, staphylococcal enterotoxins (SEs) produced by induce foodborne poisoning; toxic shock syndrome toxin-1 (TSST-1), typical superantigen, induces syndrome; hemolysins cell damage erythrocytes leukocytes; exfoliative toxin scalded syndrome. Recently, Panton–Valentine leucocidin, cytotoxin community-associated methicillin-resistant (CA-MRSA), has been reported, new types SEs enterotoxin-like toxins (SEls) were discovered reported successively. This review addresses progress novel insights into molecular structure, biological activities, pathogenicity classic newly identified aureus.

Язык: Английский

Процитировано

31

Performance of clinical metagenomics in France: a prospective observational study DOI Creative Commons
Jacques Fourgeaud, Béatrice Regnault, Vichita Ok

и другие.

The Lancet Microbe, Год журнала: 2023, Номер 5(1), С. e52 - e61

Опубликована: Дек. 1, 2023

Metagenomic next-generation sequencing (mNGS) allows untargeted identification of a broad range pathogens, including rare or novel microorganisms. Despite the recognition mNGS as valuable diagnostic tool for infections, most relevant indications this innovative strategy remain poorly defined. We aimed to assess determinants positivity and clinical utility mNGS.

Язык: Английский

Процитировано

25