Browsing by Author "Govender, Thavendran"

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    In Vitro and In Vivo Development of a β‑Lactam-Metallo-βLactamase Inhibitor: Targeting Carbapenem-Resistant Enterobacterales
    (ACS Publications, 2023-02-14) Peters, Byron. K; Reddy, Nakita; Shungube, Mbongeni; Girdhari, Letisha; Baijnath,Sooraj; Mdanda, Sipho; Chetty, Lloyd; Ntombela, Thandokuhle; Arumugum, Thilona; Bester, Linda, A; Singh, Sanil. D; Chuturgoon, Anil; Maguire, Glenn. E.M.; Arvidsson, Per. I.; Kruger, Hendrik. G.; Naicker, Tricia; Govender, Thavendran
    β-lactams are the most prescribed class of antibiotics due to their potent, broad-spectrum antimicrobial activities. However, alarming rates of antimicrobial resistance now threaten the clinical relevance of these drugs, especially for the carbapenemresistant Enterobacterales expressing metallo-β-lactamases (MBLs). Antimicrobial agents that specifically target these enzymes to restore the efficacy of last resort β-lactam drugs, that is, carbapenems, are therefore desperately needed. Herein, we present a cyclic zinc chelator covalently attached to a β-lactam scaffold (cephalosporin), that is, BP1. Observations from in vitro assays (with seven MBL expressing bacteria from different geographies) have indicated that BP1 restored the efficacy of meropenem to ≤ 0.5 mg/L, with sterilizing activity occurring from 8 h postinoculation. Furthermore, BP1 was nontoxic against human hepatocarcinoma cells (IC50 > 1000 mg/L) and exhibited a potency of (Kiapp) 24.8 and 97.4 μM against Verona integron-encoded MBL (VIM-2) and New Delhi metallo β-lactamase (NDM-1), respectively. There was no inhibition observed from BP1 with the human zinc-containing enzyme glyoxylase II up to 500 μM. Preliminary molecular docking of BP1 with NDM-1 and VIM-2 sheds light on BP1’s mode of action. In Klebsiella pneumoniae NDM infected mice, BP1 coadministered with meropenem was efficacious in reducing the bacterial load by >3 log10 units’ postinfection. The findings herein propose a favorable therapeutic combination strategy that restores the activity of the carbapenem antibiotic class and complements the few MBL inhibitors under development, with the ultimate goal of curbing antimicrobial resistance.
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    The analysis of alcohol content in hand sanitisers (in the Durban region) using gas chromatography-mass spectrometry during the COVID-19 pandemic
    (Sabinet, 2021-12-01) Govendera, Kamini.; Mdanda, Sipho; Baijnatha, Sooraj; Kruger, Hendrik Gerhardus; Govender, Thavendran; Naicker, Tricia
    The COVID-19 pandemic has resulted in an unprecedented surge in the demand for alcohol-based hand sanitisers (ABHS). The Centre for Disease Control (CDC) and World Health Organisation (WHO) recommend alcohol, i.e., isopropanol or ethanol, at a 60-95% concentration in ABHS for sufficient antiviral protection. Consumers need to be vigilant of substandard hand sanitisers being marketed to the public. The frequent exposure of microorganisms to alcohol concentrations below the recommended range for infection prevention may lead to resistant mutations, and above the range may be ineffective. Therefore, this study aimed to verify the stated alcohol content in hand sanitisers from their respective labels. We analysed 50 hand sanitiser samples available to our region in Durban, KwaZulu-Natal, South Africa, using a Shimadzu GC-MS-QP2010 Ultra equipped with a Zebron ZB-wax capillary column. The hand sanitisers analysed had a range of 44–93% alcohol content. The data from our study also revealed that 32% (16) of hand sanitisers did not adhere to the stated alcohol indicated on their labels. 16% (8) contained >80% and 12% (6) contained <60%, while 6% (3) of the ABHS contained 1-propanol and ethyl acetate as contaminants, respectively. This study clearly emphasises manufacturers’ exploitation of the pandemic and the need for stricter guidelines and regulations for consistency amongst ABHS manufacturers. The public should also be more alert to the % alcohol stated (ideal range 60-80%) on the sanitizer bottle and note one needs to rub their hands together until it feels dry.