https://scholarworks.unist.ac.kr/handle/201301/2 2026-05-11T02:48:29Z 2026-05-11T02:48:29Z Crispim, Natalia Ribeiro Nunes, Gustavo Dantas Soares, Gabriela Guerrera Shilling, Rebecca Elizabeth Ferreira, Roumayne Lopes Campos, Leslie Camelo Alcobaca, Olinda Soares Athaide da Silva, Joao Pedro Maia de Oliveira Rodrigues, Saulo Henrique Pitondo-Silva, Andre Fuentes, Andrea Soares da Costa da Cunha, Anderson Ferreira Mitchell, Robert J. Pranchevicius, Maria-Cristina da Silva https://scholarworks.unist.ac.kr/handle/201301/91648 2026-05-08T07:00:43Z 2026-01-31T15:00:00Z

Title: Heteroresistance to amikacin in Klebsiella aerogenes isolates from patients in an intensive care unit in Brazil Author(s): Crispim, Natalia Ribeiro; Nunes, Gustavo Dantas; Soares, Gabriela Guerrera; Shilling, Rebecca Elizabeth; Ferreira, Roumayne Lopes; Campos, Leslie Camelo; Alcobaca, Olinda Soares Athaide; da Silva, Joao Pedro Maia de Oliveira; Rodrigues, Saulo Henrique; Pitondo-Silva, Andre; Fuentes, Andrea Soares da Costa; da Cunha, Anderson Ferreira; Mitchell, Robert J.; Pranchevicius, Maria-Cristina da Silva Abstract: Heteroresistance is defined by the presence of subpopulations within a bacterial isolate that exhibit greater antibiotic resistance than the dominant population. In this study, we investigated amikacin heteroresistance in the opportunistic, nosocomial pathogen Klebsiella aerogenes (AHR-KA). Eight carbapenemase-resistant, but amikacin-susceptible, isolates from intensive care units of a Brazilian hospital were analyzed. Population analysis profiling identified five amikacin heteroresistant isolates (AHR-KA-1 to 5), with subpopulation frequencies ranging from 1.83 & times; 10-7 to 6.01 & times; 10-6. Among these, only AHR-KA-1 exhibited stable heteroresistance following serial passaging in antibiotic-free media. AHR-KA-1 demonstrated only slightly reduced growth rates when compared with those of the unstable AHR-KAs, parental, and control strains, suggesting no significant fitness cost associated with drug resistance. Time-kill assays for AHR-KA-1 showed an initial decline in cell viability, followed by regrowth at both 4 & times; and 8 & times; MIC. The draft genome of the stable isolate had a total length and G+C content similar to most of the sequenced genomes from K. aerogenes. Notably, AHR-KA-1 ' s aac(6 ')-Ib-cr variant contained D179Y and R102W mutations, conferring amikacin resistance. Moreover, quantitative reverse transcription PCR revealed significantly elevated expression of the aac(6 ')-Ib-cr gene in AHR-KA-1 before amikacin-free passage, compared to both the parental strain and the AHR-KA-1 strain after drug-free passage. Therefore, this study identified amikacin heteroresistance in carbapenemase-producing K. aerogenes, including a stable, mutation-driven phenotype with low fitness cost and rapid regrowth under high amikacin concentrations, underscoring its clinical relevance. These findings reinforce the importance of detecting heteroresistant subpopulations and strengthening surveillance to prevent treatment failure and the spread of undetected resistance.IMPORTANCEKlebsiella aerogenes, an opportunistic human pathogen, is frequently implicated in severe and invasive infections, particularly in immunocompromised individuals. The growing prevalence of antibiotic resistance among these strains poses a significant therapeutic challenge. The phenomenon of heteroresistance further complicates management, potentially leading to diagnostic difficulties due to the lack of standardized detection methods and subsequent treatment failures. Our studies identified and characterized K. aerogenes strains heteroresistant to amikacin, isolated from patients in an intensive care unit. Such data can serve as a foundational reference for understanding the clinical relevance, genomic variability, and pathogenic potential of K. aerogenes heteroresistance to antibiotics used in clinical settings.

2026-01-31T15:00:00Z Kim, Suhyun Park, Sehee Lee, SangJoon https://scholarworks.unist.ac.kr/handle/201301/91646 2026-05-08T04:30:10Z 2026-02-28T15:00:00Z

Title: Redefining nucleotide-binding oligomerization domain-like receptors: from immune sentinels to multifunctional regulators Author(s): Kim, Suhyun; Park, Sehee; Lee, SangJoon Abstract: Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are a large family of intracellular pattern recognition receptors primarily involved in innate immunity. Although canonical inflammasome-forming NLRs, such as NLRP3 and NLRC4, and microbial sensors, including NOD1 and NOD2, are well characterized, the functions of many other NLRs remain poorly understood. This review addresses this gap by highlighting the critical, context-dependent roles of these less-characterized NLRs beyond pathogen sensing. Here, we classify these NLRs as immune modulators, regulators of autophagy and mitophagy, tissue-specific effectors, and reproductive mediators, expanding the traditional view of NLR functions. Understanding the diverse, context-dependent roles of NLRs across biological systems is essential to fully understand their complex regulatory networks and therapeutic potential, which extends beyond classical inflammasome functions.

2026-02-28T15:00:00Z De Stefano, Alessia Marvi, Maria Vittoria Fazio, Antonietta McCubrey, James A. Suh, Pann-Ghill Ratti, Stefano Ramazzotti, Giulia Manzoli, Lucia Cocco, Lucio Follo, Matilde Y. https://scholarworks.unist.ac.kr/handle/201301/91490 2026-04-23T04:30:16Z 2022-12-31T15:00:00Z

Title: Advances in MDS/AML and inositide signalling Author(s): De Stefano, Alessia; Marvi, Maria Vittoria; Fazio, Antonietta; McCubrey, James A.; Suh, Pann-Ghill; Ratti, Stefano; Ramazzotti, Giulia; Manzoli, Lucia; Cocco, Lucio; Follo, Matilde Y. Abstract: Aberrant signaling pathways regulating proliferation and differentiation of hematopoietic stem cells (HSCs) can contribute to disease pathogenesis and neoplastic growth. Phosphoinositides (PIs) are inositol phospholipids that are implicated in the regulation of critical signaling pathways: aberrant regulation of Phospholipase C (PLC) beta1, PLCgamma1 and the PI3K/Akt/mTOR pathway play essential roles in the pathogenesis of Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML).

2022-12-31T15:00:00Z Ko, Kangeun Woo, Song Won Chae, Young Chan Lee, Minchul Moon, Hyo Youl https://scholarworks.unist.ac.kr/handle/201301/91486 2026-04-23T01:31:01Z 2023-11-30T15:00:00Z

Title: Potential involvement of neutrophils on exercise effects in breast cancer malignancy Author(s): Ko, Kangeun; Woo, Song Won; Chae, Young Chan; Lee, Minchul; Moon, Hyo Youl Abstract: [Purpose] This review aimed to comprehensively explore and elucidate multifaceted neutrophils in breast cancer, particularly in the context of physical activity. Neutrophils play a critical role in the tumor microenvironment and systemic immune response, despite their short half-life and terminal differentiation. Through a thorough review of research related to changes in immunity in breast cancer during exercise, this review aims to provide comprehensive insights into immunological changes, especially focusing on neutrophils. Recognizing that much of the existing research has predominantly focused on T cells and nature killer (NK) cells, our review seeks to shift the spotlight toward understanding how exercise affects neutrophils, a less-explored but critical immune response component in breast cancer. [Methods] This study involved an extensive review of the literature (from 2000 to 2023) using the PubMed, Science Direct, and Google Scholar databases. The keywords chosen for the searches were "immune cells and exercise,""exercise and breast cancer,""tumor microenvironment and neutrophils,"and "neutrophils and exercise and breast cancers."[Results] Neutrophils in the tumor microenvironment can exhibit distinct phenotypes and functions. These differences have yielded conflicting results regarding tumor progression. Exercise plays a positive role in breast cancer and alters the immune system. Physical activity can quantitatively and functionally regulate neutrophils under various conditions such as metabolic disruption or senescence. [Conclusion] This short communication outlines exercise- induced neutrophil diversification and its role in breast cancer progression, both within and systemically within the tumor microenvironment. Exercise may provide benefits through the potential neutrophil involvement in breast cancer. © 2023 The Korean Society for Exercise Nutrition.

2023-11-30T15:00:00Z