A5067535501- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Conservation, Biodiversity, and Resource Management
- Antibiotic Resistance in Bacteria
- HIV Research and Treatment
- Forest Management and Policy
- Immune Cell Function and Interaction
- Computational Drug Discovery Methods
- Cytokine Signaling Pathways and Interactions
- Trauma and Emergency Care Studies
- Quinazolinone synthesis and applications
- Innovation and Socioeconomic Development
- Agricultural risk and resilience
- Drug Transport and Resistance Mechanisms
- ICT Impact and Policies
- Agriculture and Rural Development Research
- Mining and Resource Management
- Pneumonia and Respiratory Infections
- Diabetes and associated disorders
- Energy and Environment Impacts
- Pharmacological Effects of Natural Compounds
- Actinomycetales infections and treatment
- Infectious Diseases and Tuberculosis
- Phenothiazines and Benzothiazines Synthesis and Activities
- Synthesis of β-Lactam Compounds
Case Western Reserve University
2023-2025
Makerere University
2020-2024
Louis Stokes Cleveland VA Medical Center
2024
University School
2023-2024
Norwegian University of Life Sciences
2017-2018
ABSTRACT Mycobacterium abscessus ( Mab ) affects patients with immunosuppression or underlying structural lung diseases such as cystic fibrosis (CF). Additionally, poses clinical challenges due to its resistance multiple antibiotics. Herein, we investigated the synergistic effect of dual β-lactams [sulopenem and cefuroxime (CXM)] combination sulopenem CXM β-lactamase inhibitors [BLIs—avibactam (AVI) durlobactam (DUR)]. The sulopenem-CXM yielded low minimum inhibitory concentration (MIC)...
Abstract Background Mtb is a global health problem. DacB1, D, D-carboxypeptidase, involved in peptidoglycan biosynthesis, promising target for β-lactam antibiotics (BLs) underutilized treatment. Dual BL therapy may inactivate multiple targets the synthesis pathway (“target redundancy”). Modeling studies with meropenem (MEM), showed that active site of DacB1 encompasses three penicillin-binding protein motifs: S121XXK124, S176XN178, and K282TG284 (PDB 4PPR). We explored structure-activity...
Abstract Background Mycobacterium abscessus (Mab) poses significant clinical challenges, leading to chronic pulmonary disease in immunocompromised patients. Current treatment involve amikacin (AMK), which is toxic, highlighting the imperative for safer options. This study continues our evaluation of synergistic effects a β-lactam and β-lactamase inhibitor (BL/BLI) against Mab elucidate underlying mechanism. The inhibition constant (Ki,app) Methods binding affinities chemical interactions...
Direct recognition of
Kenya is one of several Sub-Saharan African countries vulnerable to climate change, which severely impacts their small-holder farming (SHF) sectors. To build resilience and reduce SHFs’ vulnerability the impact there has been ongoing advocacy for an increase in adaptation funds disbursed these countries. However, effectiveness relies heavily on quality metrics used tracking assessing needs actions developed by SHFs. This study, set out evaluate existing locally led (LLA) relevant Kenya’s...
Background Neonatal mortality due to tetanus persists in Uganda despite the mandatory vaccination of pregnant mothers. Maternal antibodies wane within a year. Uganda’s maternal guidelines do not specify timing or frequency shots, contributing suboptimal transfer neonates. We aimed determine prevalence and factors associated with protective among newborns at Kawempe National Referral Hospital. Methods conducted cross-sectional study 293 mother-newborn pairs. At delivery, neonatal cord venous...
Peptidoglycan synthesis is an underutilized drug target in Mycobacterium tuberculosis (Mtb). Diazabicyclooctanes (DBOs) are a class of broad-spectrum β-lactamase inhibitors that also inhibit certain peptidoglycan transpeptidases important mycobacterial cell wall synthesis. We evaluated the DBO durlobactam as inhibitor BlaC, Mtb β-lactamase, and multiple (PonA1, LdtMt1, LdtMt2, LdtMt3, LdtMt5). Timed electrospray ionization mass spectrometry (ESI-MS) captured acyl-enzyme complexes with BlaC...
ABSTRACT Mycobacterium abscessus ( Mab ) presents significant clinical challenges. This study evaluated the synergistic effects of a β-lactam and β-lactamase inhibitor combination against explored underlying mechanisms. Synergy was assessed through MIC tests time-kill studies, binding affinities nine β-lactams BLIs to eight target receptors (L,D-transpeptidases [LDT] 1–5, D,D-carboxypeptidase, penicillin-binding protein [PBP] B, PBP-lipo) were using mass spectrometry kinetic studies. Thermal...
Direct recognition of Mycobacterium tuberculosis (Mtb) infected cells is required for protection by CD4+ T cells. While impaired cell Mtb-infected macrophages was demonstrated in mice, data are lacking humans. Using and monocyte-derived (MDMs) from individuals with latent Mtb infection (LTBI), we quantified the frequency memory activation response to autologous MDMs virulent Mtb. We observed robust Mtb-infection differentiated using GM-CSF, while those M-CSF were poorly recognized. However,...
A significant overlap exists in the burden of Alcohol Use Disorders (AUDs) and HIV epidemic Sub-Saharan Africa. Over 60% infections occur women, mostly through cervical mucosa. Absorption systemic circulation alcohol induces global physiological immune effects, including at genital alters expression cell surface receptors, mucosal barrier permeability, inflammatory responses, lymphocyte trafficking homing. However, a substantial knowledge gap on whether these cellular or immunological...
Abstract Background M. abscessus (Mab) is among the most clinically challenging pathogens. There are significant gaps remaining in mechanism of β-lactams action Mab. β-Lactams preferentially inactivate one or multiple different L,D-Transpeptidases (LDTs) and penicillin-binding proteins (PBPs). Founded on our LDT binding data vitro synergistic efficacy imipenem (IPM), ceftaroline (CFT), amoxicillin (AMX) Mab, this study aimed to identify affinities, conformational changes thermal stability...
Abstract Background Mycobacterium abscessus (Mab) represents a significant clinical challenge, with rising incidence in recent times. The current therapeutic approach, which involves prolonged IV administration of amikacin, is associated notable toxicities. Consequently, there pressing need to explore safe alternatives antibiotic therapy. This study aimed evaluate the in-vitro synergistic effect double β-lactam (DBL) combination for all ages. Methods We conducted static concentration...
ABSTRACT Mycobacterium abscessus ( Mab ) affects patients with immunosuppression, Cystic Fibrosis (CF), or underlying structural lung diseases. Additionally, poses clinical challenges due to its resistance multiple antibiotics. Herein, we investigated the synergistic effect of dual β-lactams [sulopenem and cefuroxime (CXM)] combination sulopenem CXM a β-lactamase inhibitors [BLI; avibactam (AVI) durlobactam (DUR)]. The sulopenem-CXM yielded low minimum inhibitory concentration MIC values for...
Abstract Background : World over, there are antiretroviral therapy naïve individuals infected with HIV who maintain their CD4+T cell count above 500 cells/µl over 7-10 years and viral loads well controlled below undetectable levels (termed elite controllers, ECs) or at least 2,000 copies/mL viremic VCs) for 12 months. Mechanisms responsible control in these have not been fully elucidated. We hypothesized that cells from controllers naturally resistant to HIV-1 infection by blocking R5-tropic...
Abstract Road crashes continue to persist on Ugandan roads even with the commendable efforts that government has been implementing for so many years. This study sought explore persistent causes of road crashes, suggest recommendations and evaluate cost treating accident victims by government. Methods: A rapid cross-sectional involving both quantitative qualitative approaches was used. Desk reviews 6 key informant interviews were conducted Traffic Police Officers; Hospital...