Integrative Biomedical Research
Integrative Biomedical Research (Journal of Angiotherapy) | Online ISSN 3068-6326
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Volume 10 Number 2 2026
REVIEWS (Open Access)
Phenotypic screening for antibiotic discovery against multidrug-resistant Neisseria gonorrhoeae
Zahraa Redha Shamsee 1*, Aida Hussain Ibrahim 1, Muntaha R. Ibraheem 2, Abla Hannachi-Hecini 3, Aya Mekimah 4, Soundous Gharbi 4
Integrative Biomedical Research 10 (2) 1-8 https://doi.org/10.25163/biomedical.10210957
Submitted: 11 July 2026 Revised: 05 September 2026 Accepted: 12 September 2026 Published: 14 September 2026
Abstract
Neisseria gonorrhoeae has outlived every antimicrobial class deployed against it since the 1930s, and the margin left to clinicians is now uncomfortably thin. Between 80 and 106 million infections occur each year, no licensed vaccine exists, and control therefore rests almost entirely on chemotherapy that the organism keeps dismantling. This review asks why the discovery pipeline has failed to keep pace, and argues that a substantial part of the answer lies in how candidate molecules are selected in the first place. For roughly three decades the field favoured target-based screening: purified enzymes, crystallographic structures, docking scores. That approach yielded elegant biochemistry and remarkably few usable antibiotics, largely because it evaluates binding in conditions that bear little resemblance to the gonococcal cell. Restricted porin influx through PorB1b, constitutive MtrCDE efflux, mosaic penA and QRDR alterations, and host-conditioned physiology are all invisible to an assay containing one protein in buffer. We synthesise evidence from resistance genetics, comparative assay design, and recent whole-cell screening campaigns to make the case for phenotype-first discovery. Zoliflodacin, gepotidacin, MBX-4132, synthetic nitroquinolines, and repurposed gold thiols such as auranofin all emerged from, or were validated by, assays performed on intact bacteria, and each carries a resistance profile that single-target chemistry has struggled to match. We also examine where phenotypic screening is weakest, particularly target deconvolution and throughput, and propose an integrated framework in which whole-cell activity is the entry criterion and proteomics, metabolic modelling, and surveillance data supply the mechanistic interpretation that follows. Keywords: Neisseria gonorrhoeae; phenotypic screening; antimicrobial resistance; whole-cell assay; drug repurposing; zoliflodacin; auranofin; efflux pumps
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