Microbial Bioactives
Microbial Bioactives | Online ISSN 2209-2161
362
Citations
208.1k
Views
181
Articles
Volume 5 Number 1 2022
REVIEWS (Open Access)
Emerging Strategies in Antimicrobial Research: Targeting Pathogens, Biofilms, and Microbiome Dysbiosis
Rabiatul Basria S. M. N. Mydin 1*, Nor Hazliana Harun 1
Microbial Bioactives 5 (1) 1-8 https://doi.org/10.25163/microbbioacts.5110700
Submitted: 17 December 2021 Revised: 03 February 2022 Accepted: 12 February 2022 Published: 14 February 2022
Abstract
The rise of antibiotic-resistant pathogens poses a critical challenge to global health, demanding innovative strategies to combat microbial infections. Traditional antibiotics, once highly effective, are increasingly compromised due to widespread resistance mechanisms, biofilm formation, and the persistence of dormant bacterial populations. This systematic review and meta-analysis synthesize contemporary approaches to antimicrobial development, highlighting novel targets in bacterial metabolism, cell wall assembly, and quorum sensing pathways. Key metabolic enzymes, such as those in the L,L-diaminopimelate and shikimate pathways, offer promising avenues for selective inhibition, minimizing off-target effects in human hosts. Biofilm-associated resistance is addressed through quorum sensing inhibitors, enzymatic quorum quenching, and small-molecule modulators of cyclic-di-GMP, effectively disrupting bacterial communication and persistence. Advances in genomics, metagenomics, and culturomics have uncovered previously inaccessible microbial diversity, facilitating the discovery of natural products, bacteriophages, and engineered microbial therapeutics. High-throughput platforms and genome-mining tools, including antiSMASH and I-chip, have enabled identification of cryptic biosynthetic gene clusters and potent bioactive compounds. Moreover, next-generation probiotics demonstrate potential in restoring microbiome balance and mitigating pathogen overgrowth. Meta-analytic evidence reinforces the efficacy of these interventions in both reducing microbial virulence and enhancing conventional treatment outcomes. Collectively, this review underscores a multi-pronged, evidence-based approach integrating bioinformatics, synthetic biology, and microbiome modulation to address the escalating threat of antimicrobial resistance.
Keywords: Antibiotic resistance; Biofilms; Quorum sensing; Metabolic pathways; Natural products; Next-generation probiotics; Antimicrobial therapy
References
Abouelela, M. E., & Helmy, Y. A. (2024). Next-generation probiotics as novel therapeutics for improving human health: Current trends and future perspectives. Microorganisms, 12(3), 430. https://doi.org/10.3390/microorganisms12030430
Blin, K., Wolf, T., Chevrette, M. G., Lu, X., Schwalen, C. J., Kautsar, S. A., ... & Medema, M. H. (2017). antiSMASH 4.0—Improvements in chemistry prediction and gene cluster boundary identification. Nucleic Acids Research, 45(W1), W36–W41. https://doi.org/10.1093/nar/gkx407
Borsa, L., Dubois, M., Sacco, G., & Lupi, L. (2021). Analysis the link between periodontal diseases and Alzheimer’s disease. International Journal of Environmental Research and Public Health, 18(17), 9312. https://doi.org/10.3390/ijerph18179312
Brackman, G., & Coenye, T. (2015). Quorum sensing inhibitors as anti-biofilm agents. Current Pharmaceutical Design, 21(1), 5–11. https://doi.org/10.2174/1381612820666140905114251
Chan, A., Lam, G., Lee, G., Lowe, C., & Yip, V. (2004). Effects of antibody induced localized cell crowding on autoinducer-2 levels in Salmonella Typhimurium LT2. Journal of Experimental Microbiology and Immunology, 5, 29–36.
Coates, A., Hu, Y., Bax, R., & Page, C. (2002). The future challenges facing the development of new antimicrobial drugs. Nature Reviews Drug Discovery, 1(11), 895–910. https://doi.org/10.1038/nrd944
Conlon, B. P., Nakayasu, E. S., Fleck, L. E., Lafleur, M. D., Isabella, V. M., Coleman, K., ... & Lewis, K. (2013). Activated ClpP kills persisters and eradicates a chronic biofilm infection. Nature, 503(7476), 365–370. https://doi.org/10.1038/nature12634
Freires, I. A., Denny, C., Benso, B., de Alencar, S. M., & Rosalen, P. L. (2015). Antibacterial activity of essential oils and their isolated constituents against cariogenic bacteria. Molecules, 20(4), 7329–7358. https://doi.org/10.3390/molecules20047329
Gavrish, E., Sit, C. S., Cao, S., Kandror, O., Spoering, A., Peoples, A., ... & Lewis, K. (2014). Lassomycin, a ribosomally synthesized cyclic peptide, kills Mycobacterium tuberculosis by targeting the ATP-dependent protease ClpP1P2C1. Chemistry & Biology, 21(4), 509–518. https://doi.org/10.1016/j.chembiol.2014.02.018
Giordano-Kelhoffer, B., Lorca, C., March Llanes, J., Rábano, A., del Ser, T., Serra, A., & Gallart-Palau, X. (2022). Oral microbiota, its equilibrium and implications in the pathophysiology of human diseases: A systematic review. Biomedicines, 10(8), 1803. https://doi.org/10.3390/biomedicines10081803
Gonzalez-Bello, C. (2016). Inhibition of shikimate kinase and type II dehydroquinase for antibiotic discovery: Structure-based design and simulation studies. Current Topics in Medicinal Chemistry, 16(9), 960–977. https://doi.org/10.2174/1568026615666150825142141
Gutierrez, J. A., Crowder, T., Rinaldo-Matthis, A., Ho, M. C., Almo, S. C., & Schramm, V. L. (2009). Transition state analogs of 5’-methylthioadenosine nucleosidase disrupt quorum sensing. Nature Chemical Biology, 5(4), 251–257. https://doi.org/10.1038/nchembio.145
Han, X., & Lu, C. (2009). Biological activity and identification of a peptide inhibitor of LuxS from Streptococcus suis serotype 2. FEMS Microbiology Letters, 294(1), 16–23. https://doi.org/10.1111/j.1574-6968.2009.01524.x
Hoffmann, N., Lee, B., Hentzer, M., Rasmussen, T. B., Song, Z., Johansen, H. K., ... & Høiby, N. (2007). Azithromycin blocks quorum sensing and alginate polymer formation in stationary-growth-phase Pseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy, 51(10), 3677–3687. https://doi.org/10.1128/AAC.00543-07
Hudson, A. O., Gilvarg, C., & Leustek, T. (2008). Biochemical and phylogenetic characterization of a novel diaminopimelate biosynthesis pathway in prokaryotes identifies a diverged form of L,L-diaminopimelate aminotransferase. Journal of Bacteriology, 190(9), 3256–3263. https://doi.org/10.1128/JB.01973-07
Jubeh, B., Breijyeh, Z., & Karaman, R. (2020). Resistance of Gram-positive bacteria to current antibacterial agents and overcoming approaches. Molecules, 25(12), 2888. https://doi.org/10.3390/molecules25122888
Kim, H. S., Cha, E., Kim, Y., Jeon, Y. H., Olson, B. H., Byun, Y., & Park, H. D. (2016). Raffinose, a plant galactoside, inhibits Pseudomonas aeruginosa biofilm formation via decreasing cellular cyclic diguanylate levels. Scientific Reports, 6, 25318. https://doi.org/10.1038/srep25318
Lagier, J. C., Dubourg, G., Million, M., Cadoret, F., Bilen, M., Fenollar, F., ... & Raoult, D. (2018). Culturing the human microbiota and culturomics. Nature Reviews Microbiology, 16(9), 540–550. https://doi.org/10.1038/s41579-018-0041-0
Lee, J. E., Singh, V., Evans, G. B., Tyler, P. C., Furneaux, R. H., Cornell, K. A., ... & Howell, P. L. (2005). Structural rationale for the affinity of pico- and femtomolar transition state analogues of Escherichia coli 5’-methylthioadenosine nucleosidase. Journal of Biological Chemistry, 280(18), 18274–18282. https://doi.org/10.1074/jbc.M500472200
Ling, L. L., Schneider, T., Peoples, A. J., Spoering, A. L., Engels, I., Conlon, B. P., ... & Lewis, K. (2015). A new antibiotic kills pathogens without detectable resistance. Nature, 517(7535), 455–459. https://doi.org/10.1038/nature14098
Mantravadi, P. K., Kalesh, K. A., Dobson, R. C. J., Hudson, A. O., & Parthasarathy, A. (2019). The quest for novel antimicrobial compounds: Emerging trends in research, development, and technologies. Antibiotics, 8(1), 8.
Recommended articles
Illuminating Biological Dark Matter: Integrating Metagenomics, Synthetic Biology, and AI to Unlock Microbial and Genomic Potential for Therapeutics and Biotechnology
Marine Microbial Natural Products as a Frontier in Drug Discovery: A Systematic Review
Article metrics
View details
0
Downloads
0
Citations
18
Views
0
Save
Save
0
Citation
Citation
18
View
View
0
Share
Share