Repurposing Non-Antimicrobial Drugs and Clinical Molecules to Treat Bacterial Infections

Younis, Waleed; Thangamani, Shankar; Seleem, Mohamed N.

doi:10.2174/1381612821666150506154434

Cited by 81 publications

(74 citation statements)

References 13 publications

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“…Given the need for novel antimicrobials and many appeals of drug repurposing, we performed a whole-cell screening assay to identify Food and Drug Administration (FDA) approved non-antimicrobial drugs with antimicrobial activity toward the ESKAPE pathogens [10]. The screening of a library containing 727 FDA approved drugs and small molecules has produced promising results and has proven to be successful for the identification of novel antimicrobial drugs and new leads for drug development.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Screening of an FDA-Approved Library Against ESKAPE Pathogens

Younis

AbdelKhalek

Mayhoub

et al. 2017

CPD

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Bacterial resistance to conventional antibiotics is an increasingly serious threat to public health worldwide that requires immediate exploration and the development of novel antimicrobial compounds. Drug repurposing is an inexpensive and untapped source of new antimicrobial leads, and it holds many attractive features warranting further attention for antimicrobial drug discovery. In an effort to repurpose drugs and explore new leads in the field of antimicrobial drug discovery, we performed a whole-cell screening assay of 1,600 Food and Drug Administration (FDA) approved drugs against Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae (ESKAPE) pathogens. The in vitro screening identified 49 non-antimicrobial drugs that were active against at least one species of ESKAPE pathogen. Although some of these drugs were known to have antibacterial activity, many have never been reported before. In particular, sulfonamide-containing structures represent a novel drug scaffold that should be investigated further. The characteristics of these drugs as antimicrobial agents may offer a safe, effective, and quick supplement to current approaches to treating bacterial infections.

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Section: Introductionmentioning

confidence: 99%

In Vitro Screening of an FDA-Approved Library Against ESKAPE Pathogens

Younis

AbdelKhalek

Mayhoub

et al. 2017

CPD

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“…Recently, we assembled and screened one-half of all commercially available drugs (ca. 2200 drugs) and small molecules used in human clinical trials [2,12] and identified three drugs (auranofin, ebselen and 5-fluoro-2'-deoxyuridine) [2,13,14] that exhibited potent antibacterial activity against important clinical pathogens. One of these drugs, auranofin, was found to inhibit the growth of clinical isolates of MRSA at submicrogram/mL concentrations in vitro.…”

Section: Introductionmentioning

confidence: 99%

Repurposing auranofin for the treatment of cutaneous staphylococcal infections

Thangamani

Mohammad

Abushahba

et al. 2016

International Journal of Antimicrobial Agents

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The scourge of multidrug-resistant bacterial infections necessitates the urgent development of novel antimicrobials to address this public health challenge. Drug repurposing is a proven strategy to discover new antimicrobial agents; given that these agents have undergone extensive toxicological and pharmacological analysis, repurposing is an effective method to reduce the time, cost and risk associated with traditional antibiotic innovation. In this study, the in vitro and in vivo antibacterial activities of an antirheumatic drug, auranofin, was investigated against multidrug-resistant Staphylococcus aureus. The results indicated that auranofin possesses potent antibacterial activity against all tested strains of S. aureus, including meticillin-resistant S. aureus (MRSA), vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA), with minimum inhibitory concentrations (MICs) ranging from 0.0625 μg/mL to 0.125 μg/mL. In vivo, topical auranofin proved superior to conventional antimicrobials, including fusidic acid and mupirocin, in reducing the mean bacterial load in infected wounds in a murine model of MRSA skin infection. In addition to reducing the bacterial load, topical treatment of auranofin greatly reduced the production of inflammatory cytokines, including tumour necrosis factor-α (TNFα), interleukin-6 (IL-6), interleukin-1 beta (IL-1β) and monocyte chemoattractant protein-1 (MCP-1), in infected skin lesions. Moreover, auranofin significantly disrupted established in vitro biofilms of S. aureus and Staphylococcus epidermidis, more so than the traditional antimicrobials linezolid and vancomycin. Taken together, these results support that auranofin has potential to be repurposed as a topical antimicrobial agent for the treatment of staphylococcal skin and wound infections.

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“…A recent study showed 2 nonantibiotic drugs to have bactericidal activity in an animal model, a result that suggests potential clinical usefulness. 18 Another innovative technique is the adjunctive use of hyperbaric oxygen, which has been reported to be useful in a case of Pseudomonas keratitis. 19 A higher percentage of keratitis episodes in the drugsensitive group resolved with medical therapy alone compared with the MDR-PA group (55.22% vs. 34.78%), although the difference was not statistically significant.…”

Section: Discussionmentioning

confidence: 99%