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Fulltext Antibacterial Activity of Ikarugamycin against Intracellular Staphylococcus aureus in Bovine Mammary Epithelial Cells In Vitro Infection Model

Saeed SI, Aklilu E, Mohammedsalih KM, Adekola AA, Mergani AE, Mohamad M, et al.

Biology (Basel), 2021 Sep 25;10(10).
PMID: 34681057 DOI: 10.3390/biology10100958

Staphylococcus aureus is an ubiquitous and versatile pathogen associated with a wide range of diseases. In animals, this bacterium is one of the causative agents of bovine mastitis, responsible for huge economic losses in the dairy industry. Besides the development of antibiotic resistance, the intracellular survival of S. aureus within udder cells has rendered many antibiotics ineffective, leading to therapeutic failure. Our study therefore aims to investigate the in vitro bactericidal activity of ikarugamycin (IKA) against intracellular S. aureus using a bovine mammary epithelial cells (Mac-T cells) infection model and determine the cytotoxic effect. Minimum inhibitory concentration (MIC) was used to determine the antibacterial activity of IKA, and Mac-T cells were infected with S. aureus using gentamicin protection assay. IKA intracellular antibacterial activity assays were used to determine the bactericidal activity of IKA against intracellular S. aureus. The cytotoxicity of IKA against Mac-T cells was evaluated using the resazurin assay. We showed that, S. aureus is susceptible to IKA with a MIC value of 0.6 μg/mL. IKA at 4 × MIC and 8 × MIC have bactericidal activity by reducing 3 and 5 logs10 CFU/mL of S. aureus in the first six-hour of treatment respectively. In addition, IKA demonstrated intracellular killing activity by killing 90% of intracellular S. aureus at 5 μg/mL. This level is comparatively lower than 9.2 μg/mL determined as the half-maximal inhibitory concentration (IC50) of IKA required to kill 50% of Mac-T cells, highlighting a lower concentration required for bactericidal effect compared to the cytotoxic effect. The study highlighted that importance of IKA as a potential antibiotic candidate to be explored for the in vivo efficacy in treating S. aureus mastitis.
Confronting the complexities of antimicrobial management for Staphyloccous aureus causing bovine mastitis: an innovative paradigm

Saeed SI, Kamaruzzaman NF, Gahamanyi N, Nguyen TTH, Hossain D, Kahwa I

Ir Vet J, 2024 Feb 28;77(1):4.
PMID: 38418988 DOI: 10.1186/s13620-024-00264-1

Globally, Mastitis is a disease commonly affecting dairy cattle which leads to the use of antimicrobials. The majority of mastitis etiological agents are bacterial pathogens and Staphylococcus aureus is the predominant causative agent. Antimicrobial treatment is administered mainly via intramammary and intramuscular routes. Due to increasing antimicrobial resistance (AMR) often associated with antimicrobial misuse, the treatment of mastitis is becoming challenging with less alternative treatment options. Besides, biofilms formation and ability of mastitis-causing bacteria to enter and adhere within the cells of the mammary epithelium complicate the treatment of bovine mastitis. In this review article, we address the challenges in treating mastitis through conventional antibiotic treatment because of the rising AMR, biofilms formation, and the intracellular survival of bacteria. This review article describes different alternative treatments including phytochemical compounds, antimicrobial peptides (AMPs), phage therapy, and Graphene Nanomaterial-Based Therapy that can potentially be further developed to complement existing antimicrobial therapy and overcome the growing threat of AMR in etiologies of mastitis.
Correction: Confronting the complexities of antimicrobial management for Staphylococcus aureus causing bovine mastitis: an innovative paradigm

Saeed SI, Kamaruzzaman NF, Gahamanyi N, Nguyen TTH, Hossain D, Kahwa I

Ir Vet J, 2024 Mar 09;77(1):5.
PMID: 38461351 DOI: 10.1186/s13620-024-00266-z
Antimicrobial activities of graphene oxide against biofilm and intracellular Staphylococcus aureus isolated from bovine mastitis

Saeed SI, Vivian L, Zalati CWSCW, Sani NIM, Aklilu E, Mohamad M, et al.

BMC Vet Res, 2023 Jan 14;19(1):10.
PMID: 36641476 DOI: 10.1186/s12917-022-03560-6

BACKGROUND: S. aureus is one of the causative agents of bovine mastitis. The treatment using conventional antimicrobials has been hampered due to the development of antimicrobial resistance and the ability of the bacteria to form biofilms and localize inside the host cells.
OBJECTIVES: Here, the efficacy of graphene oxide (GO), a carbon-based nanomaterial, was tested against the biofilms and intracellular S. aureus invitro. Following that, the mechanism for the intracellular antimicrobial activities and GO toxicities was elucidated.
METHODS: GO antibiofilm properties were evaluated based on the disruption of biofilm structure, and the intracellular antimicrobial activities were determined by the survival of S. aureus in infected bovine mammary cells following GO exposure. The mechanism for GO intracellular antimicrobial activities was investigated using endocytosis inhibitors. GO toxicity towards the host cells was assessed using a resazurin assay.
RESULTS: At 100 ug/mL, GO reduced between 30 and 70% of S. aureus biofilm mass, suggesting GO's ability to disrupt the biofilm structure. At 200 ug/mL, GO killed almost 80% of intracellular S. aureus, and the antimicrobial activities were inhibited when cells were pre-treated with cytochalasin D, suggesting GO intracellular antimicrobial activities were dependent on the actin-polymerization of the cell membrane. At
Fulltext Targeting the Bacterial Protective Armour; Challenges and Novel Strategies in the Treatment of Microbial Biofilm

Kamaruzzaman NF, Tan LP, Mat Yazid KA, Saeed SI, Hamdan RH, Choong SS, et al.

Materials (Basel), 2018 Sep 13;11(9).
PMID: 30217006 DOI: 10.3390/ma11091705

Infectious disease caused by pathogenic bacteria continues to be the primary challenge to humanity. Antimicrobial resistance and microbial biofilm formation in part, lead to treatment failures. The formation of biofilms by nosocomial pathogens such as Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), and Klebsiella pneumoniae (K. pneumoniae) on medical devices and on the surfaces of infected sites bring additional hurdles to existing therapies. In this review, we discuss the challenges encountered by conventional treatment strategies in the clinic. We also provide updates on current on-going research related to the development of novel anti-biofilm technologies. We intend for this review to provide understanding to readers on the current problem in health-care settings and propose new ideas for new intervention strategies to reduce the burden related to microbial infections.
Current status of the small molecule anti-HIV drugs in the pipeline or recently approved

Umumararungu T, Nyandwi JB, Katandula J, Twizeyimana E, Claude Tomani J, Gahamanyi N, et al.

Bioorg Med Chem, 2024 Sep 01;111:117860.
PMID: 39094527 DOI: 10.1016/j.bmc.2024.117860

Human Immunodeficiency Virus (HIV) is the causative agent of Acquired Immunodeficiency Syndrome (AIDS) with high morbidity and mortality rates. Treatment of AIDS/HIV is being complicated by increasing resistance to currently used antiretroviral (ARV) drugs, mainly in low- and middle-income countries (LMICs) due to drug misuse, poor drug supply and poor treatment monitoring. However, progress has been made in the development of new ARV drugs, targeting different HIV components (Fig. 1). This review aims at presenting and discussing the progress made towards the discovery of new ARVs that are at different stages of clinical trials as of July 2024. For each compound, the mechanism of action, target biomolecule, genes associated with resistance, efficacy and safety, class, and phase of clinical trial are discussed. These compounds include analogues of nucleoside reverse transcriptase inhibitors (NRTIs) - islatravir and censavudine; non-nucleoside reverse transcriptase inhibitors (NNRTIs) - Rilpivirine, elsulfavirine and doravirine; integrase inhibitors namely cabotegravir and dolutegravir and chemokine coreceptors 5 and 2 (CC5/CCR2) antagonists for example cenicriviroc. Also, fostemsavir is being developed as an attachment inhibitor while lenacapavir, VH4004280 and VH4011499 are capsid inhibitors. Others are maturation inhibitors such as GSK-254, GSK3532795, GSK3739937, GSK2838232, and other compounds labelled as miscellaneous (do not belong to the classical groups of anti-HIV drugs or to the newer classes) such as obefazimod and BIT225. There is a considerable progress in the development of new anti-HIV drugs and the effort will continue since HIV infections has no cure or vaccine till now. Efforts are needed to reduce the toxicity of available drugs or discover new drugs with new classes which can delay the development of resistance.