Wonsik Lee

Recent data indicate that the nutrients available to Mycobacterium tuberculosis (Mtb) inside its host cell are restricted in their diversity. Fatty acids and cholesterol appear more favored; however, their degradation can result in certain metabolic stresses. Their breakdown can generate propionyl-CoA, which gives rise to potentially toxic intermediates. Detoxification of propionyl-CoA relies on the activity of the methylcitrate cycle, the methylmalonyl pathway, or incorporation of the propionyl

Antibiotic-resistant Staphylococcus aureus remains a leading cause of antibiotic resistance-associated mortality in the United States. Given the reality of multi-drug resistant infections, it is imperative that we establish and maintain a pipeline of new compounds to replace or supplement our current antibiotics. A first step towards this goal is to prioritize targets by identifying the genes most consistently required for survival across the S. aureus phylogeny. Here we report the first direct

Lysobactin, also known as katanosin B, is a potent antibiotic with in vivo efficacy against Staphylococcus aureus and Streptococcus pneumoniae. It was previously shown to inhibit peptidoglycan (PG) biosynthesis, but its molecular mechanism of action has not been established. Using enzyme inhibition assays, we show that lysobactin forms 1:1 complexes with Lipid I, Lipid II, and Lipid II(A)(WTA), substrates in the PG and wall teichoic acid (WTA) biosynthetic pathways. Therefore, lysobactin, like r

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry is mediated by the interaction of the viral spike (S) protein with angiotensin-converting enzyme 2 (ACE2) on the host cell surface. Although a clinical trial testing soluble ACE2 (sACE2) for COVID-19 is currently ongoing, our understanding of the delivery of sACE2 via small extracellular vesicles (sEVs) is still rudimentary. With excellent biocompatibility allowing for the effective delivery of molecular cargos, sEVs are broadly

Targeted modification of bacterial chromosomes is necessary to understand new drug targets, investigate virulence factors, elucidate cell physiology, and validate results of -omics-based approaches. For some bacteria, reverse genetics remains a major bottleneck to progress in research. Here, we describe a compound-centric strategy that combines new negative selection markers with known positive selection markers to achieve simple, efficient one-step genome engineering of bacterial chromosomes. T

Synthetic biology approaches offer potential for large-scale and sustainable production of natural products with bioactive potency, including ginsenosides, providing a means to produce novel compounds with enhanced therapeutic properties. Ginseng, known for its non-toxic and potent qualities in traditional medicine, has been used for various medical needs. Ginseng has shown promise for its antioxidant and neuroprotective properties, and it has been used as a potential agent to boost immunity aga

Small molecule can be utilized to restore the effectiveness of existing major classes of antibiotics against antibiotic-resistant bacteria. In this study, it is demonstrated that celastrol, a natural compound, can modify the bacterial cell wall and subsequently render bacteria more suceptible to β-lactam antibiotics. It is shown that celastrol leads to incomplete cell wall crosslinking by modulating levels of c-di-AMP, a secondary messenger, in methicillin-resistant Staphylococcus aureus (MRSA).

The ability of Staphylococcus aureus to adapt and thrive in diverse host niches adds to the challenge in combating this ubiquitous pathogen. While extensive research has been pursued on the adaptive mechanisms of methicillin-resistant S. aureus (MRSA) in various infection models, a comprehensive analysis of its fitness across different host niches is lacking. In this study, we employ transposon sequencing to analyze the adaptive strategies of MRSA in various infection niches. Our analysis encomp

Bacterial persisters are dormant phenotypic variants that are tolerant to antibiotics, contributing to treatment failure and the emergence of antimicrobial resistance. Although the formation of persisters has been extensively studied in regards to bacterial infections and treatment, such as antibiotic exposure or intracellular survival within macrophages, the role of environmental stressors in persister formation remains largely unexplored. In this study, we investigate the role of environmental

Antibiotic-resistant infections are a growing problem; to combat multi-drug resistant bacterial infections, antibiotics with novel mechanisms of action are needed. Identification of potent bioactive natural products is an attractive avenue for developing novel therapeutic strategies against bacterial infections. As part of our ongoing research to explore bioactive natural products from diverse resources, we investigated the antimicrobial compounds from Woodfordia uniflora , a flowering shrub uni

BACKGROUND: Pathogenic bacteria can invade and survive inside phagocytic and non-phagocytic cells and use them as a sanctuary against antibiotics. Induction of various host protective mechanisms, including autophagy, can be a novel and effective method to combat intracellular bacteria. Recent studies report that raloxifene, a selective oestrogen receptor modulator, can induce cellular autophagy. OBJECTIVES: To demonstrate the effect of raloxifene on intracellular invasion and proliferation of pa

The papain-like protease (PLpro) of coronaviruses is an attractive antiviral target to inhibit both viral replication and interference of the host immune response. We have identified and characterized three novel classes of small molecules, thiophene, cyanofuran, and triazoloquinazoline, as PLpro inhibitors. Thiophene inhibited the PLpro of two major coronaviruses, Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) including SARS-

The study of complex diseases has traditionally relied on reductionist methods, which, although informative, tend to overlook the dynamic interactions and systemic interconnectivity inherent in biological systems. Allostasis, a framework that focuses on physiological adaptations to stress and the maintenance of stability through change, provides a valuable perspective for understanding these diseases. This review summarizes how the allostasis framework defines the cumulative physiological burden