Skip to content
2000
Volume 25, Issue 17
  • ISSN: 1568-0266
  • E-ISSN: 1873-4294

Abstract

Introduction/Objective

The increasing resistance of pathogens to antibiotics poses a major public health challenge. This study aims to develop an innovative approach to combat this resistance by exploring synergies between standard antibiotics and marine metabolites.

Methods

The methodology combines disk diffusion testing and mixture design to assess the antimicrobial efficacy of the combinations.

Results

The results demonstrate promising synergies between carotenoids, polyphenols, and alkaloids with standard antibiotics, offering potential targeted use in the fight against clinical multidrug-resistant bacteria. Specifically, Gram-negative bacteria (BGN) showed increased resistance to antibiotics such as amoxicillin-clavulanic acid (AMC), ceftazidime, cefotaxime, tetracycline, and cefazolin. These antibiotics, when combined with marine compounds, exhibited substantial inhibitory effects against specific isolates, circumventing antibiotic resistance mechanisms. Similarly, substantial synergies were observed in Gram-positive bacteria. Leveraging advanced algorithms such as multi-objective optimization, notably the NSGA-II algorithm, we accurately predicted minimum inhibitory concentrations (MICs) against clinically resistant bacterial isolates. Optimal conditions against , characterized by carotenoids = 0.6335, total polyphenols = 0, indole alkaloids = 0.1723, and AMC = 0.1941, yielded a predicted MIC of 41.1126 mg/L, closely mirroring the experimental MIC of 41.66 ± 0.18 mg/L. Similarly, for , optimal conditions produced a predicted MIC of 30.8304 mg/L, closely aligning with the experimental MIC of 30.69 ± 1.80 mg/L.

Conclusion

The consistent and reliable predictions for bacterial strains affirmed the robustness of the applied methodology. These results not only pave the way for further exploration but also offer valuable insights for optimizing pharmaceutical and medical interventions, presenting innovative avenues for combating antibiotic-resistant bacterial infections.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ctmc/10.2174/0115680266333406250126033304
2025-02-06
2026-02-02

  • From This Site

    /content/journals/ctmc/10.2174/0115680266333406250126033304
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. BrandtA.M. GardnerM. The golden age of medicine?Medicine in the twentieth century.Taylor & Francis2020213710.4324/9781003078456‑2
     [Google Scholar]
  2. HuemerM. Mairpady ShambatS. BruggerS.D. ZinkernagelA.S. Antibiotic resistance and persistence—Implications for human health and treatment perspectives.EMBO Rep.20202112e5103410.15252/embr.202051034 33400359
     [Google Scholar]
  3. MurugaiyanJ. KumarP.A. RaoG.S. IskandarK. HawserS. HaysJ.P. MohsenY. AdukkadukkamS. AwuahW.A. JoseR.A.M. SylviaN. NansubugaE.P. TiloccaB. RoncadaP. Roson-CaleroN. Moreno-MoralesJ. AminR. KumarB.K. KumarA. ToufikA.R. ZawT.N. AkinwotuO.O. SatyaseelaM.P. van DongenM.B.M. Progress in alternative strategies to combat antimicrobial resistance: Focus on antibiotics.Antibiotics202211220010.3390/antibiotics11020200 35203804
     [Google Scholar]
  4. Talebi Bezmin AbadiA. RizvanovA.A. HaertléT. BlattN.L. World health organization report: Current crisis of antibiotic resistance.Bionanoscience20199477878810.1007/s12668‑019‑00658‑4
     [Google Scholar]
  5. Al MeslamaniA.Z. Antibiotic resistance in low- and middle-income countries: Current practices and its global implications.Expert Rev. Anti Infect. Ther.202321121281128610.1080/14787210.2023.2268835 37804134
     [Google Scholar]
  6. SalamM.A. Al-AminM.Y. SalamM.T. PawarJ.S. AkhterN. RabaanA.A. AlqumberM.A.A. Antimicrobial resistance: A growing serious threat for global public health.Health care20231113194610.3390/healthcare11131946 37444780
     [Google Scholar]
  7. Lemiech-MirowskaE. KiersnowskaZ. MichałkiewiczM. DeptaA. MarczakM. Nosocomial infections as one of the most important problems of healthcare system.Ann. Agric. Environ. Med.202128336136610.26444/aaem/122629 34558254
     [Google Scholar]
  8. StefaniniI. BoniM. SilvaplanaP. LoveraP. PelassaS. De RenziG. MognettiB. Antimicrobial resistance, an update from the ward: Increased incidence of new potential pathogens and site of infection-specific antibacterial resistances.Antibiotics20209963110.3390/antibiotics9090631 32971788
     [Google Scholar]
  9. Van DuinD. PatersonD.L. Multidrug-resistant bacteria in the community: Trends and lessons learned.Infect. Dis. Clin. North Am.201630377390
     [Google Scholar]
  10. GucluE. HalisF. KoseE. OgutluA. KarabayO. Risk factors of multidrug-resistant bacteria in community-acquired urinary tract infections.Afr. Health Sci.202121121421910.4314/ahs.v21i1.28 34394300
     [Google Scholar]
  11. AdouaneM. KadriN. BenzitouneN. LakhdariC. DjellalS. OusmerL. TahraouiH. AmraneA. ReminiH. DahmouneF. MadaniK. Understanding bacterial diversity, infection dynamics, prevention of antibiotic resistance: An integrated study in an Algerian hospital context.Eur. J. Clin. Microbiol. Infect. Dis.202443112093210510.1007/s10096‑024‑04919‑3 39136832
     [Google Scholar]
  12. Urban-ChmielR. MarekA. Stępień-PyśniakD. WieczorekK. DecM. NowaczekA. OsekJ. Antibiotic resistance in bacteria—a review.Antibiotics2022118107910.3390/antibiotics11081079 36009947
     [Google Scholar]
  13. HemaiswaryaS. KruthiventiA.K. DobleM. Synergism between natural products and antibiotics against infectious diseases.Phytomedicine200815863965210.1016/j.phymed.2008.06.008 18599280
     [Google Scholar]
  14. MannanM.A. KumarG. Current Trends in the Identification and Development of Antimicrobial Agents.Bentham Science Publishers202310.2174/97898150800561230201
     [Google Scholar]
  15. QadriH. Haseeb ShahA. Mudasir AhmadS. AlshehriB. AlmilaibaryA. Ahmad MirM. Natural products and their semi-synthetic derivatives against antimicrobial-resistant human pathogenic bacteria and fungi.Saudi J. Biol. Sci.202229910337610.1016/j.sjbs.2022.103376 35874656
     [Google Scholar]
  16. RashidS. MajeedL.R. NisarB. NisarH. BhatA.A. GanaiB.A. Phytomedicines: Diversity, extraction, and conservation strategies.Phytomedicine.Elsevier202113310.1016/B978‑0‑12‑824109‑7.00009‑1
     [Google Scholar]
  17. GiddingsL-A. NewmanD.J. GiddingsL-A. NewmanD.J. Bioactive Compounds from Terrestrial Extremophiles.Springer2015
     [Google Scholar]
  18. DjellalS. DahmouneF. AounO. ReminiH. BelbahiA. DairiS. MoussaH. LakehalM. KassouarS. LakhdariC. AdouaneM. KadriN. Optimization of ultrasound-assisted extraction of galactomannan from carob seeds “ ceratonia siliqua L” and evaluation of their functional properties and in vitro anti-inflammatory activity.Sep. Sci. Technol.2024591415810.1080/01496395.2024.2315608
     [Google Scholar]
  19. LakhdariC. ReminiH. BenzitouneN. DjellalS. HentabliM. AdouaneM. DahmouneF. KadriN. Meta-heuristic optimization for drying kinetics and quality assessment of Capparis spinosa buds.Chem. Eng. Commun.2024211121864188310.1080/00986445.2024.2389154
     [Google Scholar]
  20. AbassS. ParveenR. IrfanM. MalikZ. HusainS.A. AhmadS. Mechanism of antibacterial phytoconstituents: An updated review.Arch. Microbiol.2024206732510.1007/s00203‑024‑04035‑y 38913205
     [Google Scholar]
  21. DivekarP.A. NarayanaS. DivekarB.A. KumarR. GadratagiB.G. RayA. SinghA.K. RaniV. SinghV. SinghA.K. KumarA. SinghR.P. MeenaR.S. BeheraT.K. Plant secondary metabolites as defense tools against herbivores for sustainable crop protection.Int. J. Mol. Sci.2022235269010.3390/ijms23052690 35269836
     [Google Scholar]
  22. BalkrishnaA. SharmaN. SrivastavaD. KukretiA. SrivastavaS. AryaV. Exploring the safety, efficacy, and bioactivity of herbal medicines: Bridging traditional wisdom and modern science in healthcare.Future Integrative Medicine202431354910.14218/FIM.2023.00086
     [Google Scholar]
  23. CappielloF. LoffredoM.R. Del PlatoC. CammaroneS. CasciaroB. QuaglioD. MangoniM.L. BottaB. GhirgaF. The revaluation of plant-derived terpenes to fight antibiotic-resistant infections.Antibiotics20209632510.3390/antibiotics9060325 32545761
     [Google Scholar]
  24. MoussaH. HamidS. MameriA. LekmineS. TahraouiH. KebirM. TouzoutN. DahmouneF. OlaM.S. ZhangJ. AmraneA. From green chemistry to healthy environments: Silver nanoparticles as a dual antioxidant and antibacterial agents for advancing biomedicine and sustainable wastewater treatment.Bioengineering20241112120510.3390/bioengineering11121205
     [Google Scholar]
  25. JiaW. WangJ. XuH. LiG. Resistance of Stenotrophomonas maltophilia to fluoroquinolones: Prevalence in a university hospital and possible mechanisms.Int. J. Environ. Res. Public Health20151255177519510.3390/ijerph120505177 25985315
     [Google Scholar]
  26. SunN. DuR.L. ZhengY.Y. HuangB.H. GuoQ. ZhangR.F. WongK.Y. LuY.J. Antibacterial activity of N -methylbenzofuro[3,2- b]quinoline and N -methylbenzoindolo[3,2- b]-quinoline derivatives and study of their mode of action.Eur. J. Med. Chem.201713511110.1016/j.ejmech.2017.04.018 28426995
     [Google Scholar]
  27. SharmaD. RaniR. ChaturvediM. RohillaP. YadavJ.P. In silico and in vitro approach of Allium cepa and isolated quercetin against MDR bacterial strains and Mycobacterium smegmatis.S. Afr. J. Bot.2019124293510.1016/j.sajb.2019.04.019
     [Google Scholar]
  28. DasS. BatraS. GuptaP.P. KumarM. SrivastavaV.K. JyotiA. SinghN. KaushikS. Identification and evaluation of quercetin as a potential inhibitor of naphthoate synthase fromENTEROCOCCUS FAECALIS.J. Mol. Recognit.20193211e280210.1002/jmr.2802 31353747
     [Google Scholar]
  29. LinS. LiH. TaoY. LiuJ. YuanW. ChenY. LiuY. LiuS. In vitro and in vivo evaluation of membrane-active flavone amphiphiles: Semisynthetic kaempferol-derived antimicrobials against drug-resistant gram-positive bacteria.J. Med. Chem.202063115797581510.1021/acs.jmedchem.0c00053 32400157
     [Google Scholar]
  30. DeviK.P. NishaS.A. SakthivelR. PandianS.K. Eugenol (an essential oil of clove) acts as an antibacterial agent against Salmonella typhi by disrupting the cellular membrane.J. Ethnopharmacol.2010130110711510.1016/j.jep.2010.04.025 20435121
     [Google Scholar]
  31. CuiH. ZhangC. LiC. LinL. Antimicrobial mechanism of clove oil on Listeria monocytogenes.Food Control20189414014610.1016/j.foodcont.2018.07.007
     [Google Scholar]
  32. RahmanM.H. BajgaiJ. FadriquelaA. SharmaS. TrinhT.T. AkterR. JeongY.J. GohS.H. KimC.S. LeeK.J. Therapeutic potential of natural products in treating neurodegenerative disorders and their future prospects and challenges.Molecules20212617532710.3390/molecules26175327 34500759
     [Google Scholar]
  33. PatelM. PatelP. PithawalaE. Antioxidant and antibacterial properties of bio-pigment from Beta vulgaris.Biotech Res. Asia2023204
     [Google Scholar]
  34. KhanM.A. ShahidM. CelikI. KhanH.M. ShahzadA. HusainF.M. AdilM. Attenuation of quorum sensing regulated virulence functions and biofilm of pathogenic bacteria by medicinal plant Artemisia annua and its phytoconstituent 1, 8‐cineole.Microsc. Res. Tech.202487113314810.1002/jemt.24418 37728140
     [Google Scholar]
  35. BerghØ. BØrsheim, K.Y.; Bratbak, G.; Heldal, M. High abundance of viruses found in aquatic environments.Nature1989340623346746810.1038/340467a0 2755508
     [Google Scholar]
  36. BoeufG. Marine biodiversity characteristics.C. R. Biol.20113345-643544010.1016/j.crvi.2011.02.009 21640952
     [Google Scholar]
  37. FalcoA. AdamekM. PereiroP. HooleD. EncinarJ. NovoaB. MallaviaR. The immune system of marine organisms as source for drugs against infectious diseases.Mar. Drugs202220636310.3390/md20060363 35736166
     [Google Scholar]
  38. PomponiS.A. The bioprocess-technological potential of the sea.Progress in industrial microbiologyElsevier199935513
     [Google Scholar]
  39. PetersenL-E. KellermannM.Y. SchuppP.J. Secondary Metabolites of Marine Microbes: From Natural Products Chemistry to Chemical Ecology.Springer International Publishing2020159180
     [Google Scholar]
  40. KarthikeyanA. JosephA. NairB.G. Promising bioactive compounds from the marine environment and their potential effects on various diseases.J. Genet. Eng. Biotechnol.20222011410.1186/s43141‑021‑00290‑4 35080679
     [Google Scholar]
  41. AdouaneM. KadriN. BenzitouneN. LakhdariC. DjellalS. OusmerL. KernouO.N. ReminiH. DahmouneF. MadaniK. The optimization of antioxidant and anti-inflammatory activities of carotenoids, total polyphenols, and indole alkaloids from coral Astroides calycularis and their interactions using simplex-centroid designs.Chem. Zvesti202478147905792510.1007/s11696‑024‑03643‑8
     [Google Scholar]
  42. KumarM.S. ButtarH.S. DalalY. SinghR.B. Cardioprotective and neuroprotective effects of nutraceuticals derived from marine origin.Functional Foods and Nutraceuticals in Metabolic and Non-Communicable Diseases.Elsevier202270772310.1016/B978‑0‑12‑819815‑5.00054‑9
     [Google Scholar]
  43. TaufaT. New sesterterpenes from marine sponges from the tropical waters of the Kingdom of Tonga.Open Access Te Herenga Waka-Victoria University of Wellington2010
     [Google Scholar]
  44. VarijakzhanD. LohJ.Y. YapW.S. YusoffK. SeboussiR. LimS.H.E. LaiK.S. ChongC.M. Bioactive compounds from marine sponges: Fundamentals and applications.Mar. Drugs202119524610.3390/md19050246 33925365
     [Google Scholar]
  45. IndraningratA. SmidtH. SipkemaD. Bioprospecting sponge-associated microbes for antimicrobial compounds.Mar. Drugs20161458710.3390/md14050087 27144573
     [Google Scholar]
  46. CousseauA. SianoR. ProbertI. BachS. MehiriM. Marine dinoflagellates as a source of new bioactive structures.Stud. Nat. Prod. Chem.20206512517110.1016/B978‑0‑12‑817905‑5.00004‑4
     [Google Scholar]
  47. AssunçãoJ. GuedesA. MalcataF. Biotechnological and pharmacological applications of biotoxins and other bioactive molecules from dinoflagellates.Mar. Drugs2017151239310.3390/md15120393 29261163
     [Google Scholar]
  48. ChanasB. PawlikJ.R. Defenses of Caribbean sponges against predatory reef fish. II. Spicules, tissue toughness, and nutritional quality.Mar. Ecol. Prog. Ser.199512719521110.3354/meps127195
     [Google Scholar]
  49. JangraM. KaurP. TambatR. RakaV. MaheyN. ChandalN. AtteryS. PathaniaV. SinghV. NandanwarH. Recent updates on bacterial secondary metabolites to overcome antibiotic resistance in gram-negative superbugs: Encouragement or discontinuation?Antimicrobial Resistance: Underlying Mechanisms and Therapeutic Approaches.SingaporeSpringer2022385418
     [Google Scholar]
  50. BesednovaN.N. AndryukovB.G. ZaporozhetsT.S. KryzhanovskyS.P. KuznetsovaT.A. FedyaninaL.N. MakarenkovaI.D. ZvyagintsevaT.N. Algae polyphenolic compounds and modern antibacterial strategies: Current achievements and immediate prospects.Biomedicines20208934210.3390/biomedicines8090342 32932759
     [Google Scholar]
  51. Genta-JouveG. ThomasO.P. We will detail herein the main results obtained for four groups of terpenoids produced in large quantity by marine sponges: The isocyanide terpenes, sesquiterpene quinones, furanoterpenes and finally, steroids. Adv. Sponge Sci.: Physiol., Chem. & Microb. Divers.Biotechnol.201262193
     [Google Scholar]
  52. LawsonC.A. PossellM. SeymourJ.R. RainaJ.B. SuggettD.J. Coral endosymbionts (Symbiodiniaceae) emit species-specific volatilomes that shift when exposed to thermal stress.Sci. Rep.2019911739510.1038/s41598‑019‑53552‑0 31758008
     [Google Scholar]
  53. BiagiE. CaroselliE. BaroneM. PezzimentiM. TeixidoN. SoveriniM. RampelliS. TurroniS. GambiM.C. BrigidiP. GoffredoS. CandelaM. Patterns in microbiome composition differ with ocean acidification in anatomic compartments of the Mediterranean coral Astroides calycularis living at CO2 vents.Sci. Total Environ.202072413804810.1016/j.scitotenv.2020.138048 32251879
     [Google Scholar]
  54. Lo GiudiceA. RizzoC. Bacteria associated with benthic invertebrates from extreme marine environments: Promising but underexplored sources of biotechnologically relevant molecules.Mar. Drugs2022201061710.3390/md20100617 36286440
     [Google Scholar]
  55. SweetM.J. BrownB.E. DunneR.P. SingletonI. BullingM. Evidence for rapid, tide-related shifts in the microbiome of the coral Coelastrea aspera.Coral Reefs201736381582810.1007/s00338‑017‑1572‑y
     [Google Scholar]
  56. StinconeP. BrandelliA. Marine bacteria as source of antimicrobial compounds.Crit. Rev. Biotechnol.202040330631910.1080/07388551.2019.1710457 31992085
     [Google Scholar]
  57. van de WaterJ.A.J.M. Tignat-PerrierR. AllemandD. Ferrier-PagèsC. Coral holobionts and biotechnology: From blue economy to coral reef conservation.Curr. Opin. Biotechnol.20227411012110.1016/j.copbio.2021.10.013 34861476
     [Google Scholar]
  58. DeyP. KunduA. KumarA. GuptaM. LeeB.M. BhaktaT. DashS. KimH.S. Analysis of alkaloids (indole alkaloids, isoquinoline alkaloids, tropane alkaloids).Recent advances in natural products analysis.Elsevier202050556710.1016/B978‑0‑12‑816455‑6.00015‑9
     [Google Scholar]
  59. GuZ. DemingC. YongbinH. ZhigangC. FeirongG. Optimization of carotenoids extraction from Rhodobacter sphaeroides.Lebensm. Wiss. Technol.20084161082108810.1016/j.lwt.2007.07.005
     [Google Scholar]
  60. LiB.B. SmithB. HossainM.M. Extraction of phenolics from citrus peels.Separ. Purif. Tech.200648218218810.1016/j.seppur.2005.07.005
     [Google Scholar]
  61. MussagyC.U. RemonattoD. PaulaA.V. HerculanoR.D. Santos-EbinumaV.C. CoutinhoJ.A.P. PereiraJ.F.B. Selective recovery and purification of carotenoids and fatty acids from Rhodotorula glutinis using mixtures of biosolvents.Separ. Purif. Tech.202126611854810.1016/j.seppur.2021.118548
     [Google Scholar]
  62. BonnetR. JpB. CaronF. CattoenC. CattoirV. CourvalinP. DubreuilL. JarlierV. LefortA. MerensA. Antibiogram committee of the french society of microbiology recommendations 2019 V. 1.0 January; CA-SFM/EUCAST.2019
     [Google Scholar]
  63. Moreno-GarciaL. GariépyY. BourdeauN. BarnabéS. RaghavanG.S.V. Optimization of the proportions of four wastewaters in a blend for the cultivation of microalgae using a mixture design.Bioresour. Technol.201928316817310.1016/j.biortech.2019.03.067 30903823
     [Google Scholar]
  64. FadilM. Fikri-BenbrahimK. RachiqS. IhssaneB. LebraziS. ChraibiM. HalouiT. FarahA. Combined treatment of Thymus vulgaris L., Rosmarinus officinalis L. and Myrtus communis L. essential oils against Salmonella typhimurium: Optimization of antibacterial activity by mixture design methodology.Eur. J. Pharm. Biopharm.201812621122010.1016/j.ejpb.2017.06.002 28583590
     [Google Scholar]
  65. OuedrhiriW. BalouiriM. BouhdidS. MojaS. ChahdiF.O. TalebM. GrecheH. Mixture design of Origanum compactum, Origanum majorana and Thymus serpyllum essential oils: Optimization of their antibacterial effect.Ind. Crops Prod.2016891910.1016/j.indcrop.2016.04.049
     [Google Scholar]
  66. Dahmen-Ben MoussaI. MasmoudiM.A. ChouraS. ChamkhaM. SayadiS. Extraction optimization using response surface methodology and evaluation of the antioxidant and antimicrobial potential of polyphenols in Scenedesmus Sp. and Chlorella Sp.Biomass Convers. Biorefin.2021114
     [Google Scholar]
  67. DawoudM. MawgoudY. DawoudT.G. Synergistic interactions between plant extracts, some antibiotics and/or their impact upon antibiotic-resistant bacterial isolates.Afr. J. Biotechnol.201312
     [Google Scholar]
  68. VaouN. StavropoulouE. VoidarouC.C. TsakrisZ. RozosG. TsigalouC. BezirtzoglouE. Interactions between medical plant-derived bioactive compounds: Focus on antimicrobial combination effects.Antibiotics2022118101410.3390/antibiotics11081014 36009883
     [Google Scholar]
  69. VilvanathanS. Cephalosporins, and other β-lactam antibiotics.Introduction to Basics of Pharmacology and Toxicology: Essentials of Systemic Pharmacology: From Principles to PracticeSpringer20212821834
     [Google Scholar]
  70. AkhtarA. FatimaN. KhanH.M. Beta-lactamases and their classification: An overview.Beta-Lactam Resistance in Gram-Negative Bacteria.SingaporeSpringer20222533
     [Google Scholar]
  71. SinghalM. AgrawalM. BhavnaK. SethiyaN.K. BhargavaS. GondkarK.S. JoshiK. RanaV.S. SahooJ. AroraM.K. Chloramphenicol and tetracycline (broad spectrum antibiotics).Antibiotics-Therapeutic Spectrum and Limitations.Elsevier202315516510.1016/B978‑0‑323‑95388‑7.00019‑X
     [Google Scholar]
  72. FilbyB.W. WeldrickP.J. PaunovV.N. Overcoming beta-lactamase-based antimicrobial resistance by nanocarrier-loaded clavulanic acid and antibiotic cotreatments.ACS Appl. Bio Mater.2022583826384010.1021/acsabm.2c00369 35819369
     [Google Scholar]
  73. JeetK. KumarS. SinghG. JaswalR. KumarD. ThakurA. A comprehensive review on amoxicilin and clavulanic acid as potential antibacterial agent.Asian J. Pharm. Res. Dev.202210410811410.22270/ajprd.v10i4.1144
     [Google Scholar]
  74. AnandabaskarN. Protein synthesis inhibitors. Introduction to Basics of Pharmacology and Toxicology: Volume 2: Essentials of Systemic Pharmacology: From Principles to PracticeSpringer,2021
     [Google Scholar]
  75. TyulenevA. SmirnovaG. MuzykaN. OktyabrskyO. Study of the effect of protein synthesis inhibitors on growing escherichia coli bacteria using electrochemical sensors.Acta Biomed. Sci.20227110118
     [Google Scholar]
  76. DigheS.N. ColletT.A. Recent advances in DNA gyrase-targeted antimicrobial agents.Eur. J. Med. Chem.202019911232610.1016/j.ejmech.2020.112326 32460040
     [Google Scholar]
  77. AmmarY.A. MickyJ.A. Aboul-MagdD.S. Abd El-HafezS.M.A. HesseinS.A. AliA.M. RagabA. Development and radiosterilization of new hydrazono‐quinoline hybrids as DNA gyrase and topoisomerase IV inhibitors: Antimicrobial and hemolytic activities against uropathogenic isolates with molecular docking study.Chem. Biol. Drug Des.2023101224527010.1111/cbdd.14154 36305722
     [Google Scholar]
  78. LeynS.A. KentJ.E. ZlamalJ.E. ElaneM.L. VercruysseM. OstermanA.L. Two classes of DNA gyrase inhibitors elicit distinct evolutionary trajectories toward resistance in gram-negative pathogens. npj Antimicrob.Resist.202425
     [Google Scholar]
  79. MaxwellA. GhateV. AranjaniJ. LewisS. Breaking the barriers for the delivery of amikacin: Challenges, strategies, and opportunities.Life Sci.202128411988310.1016/j.lfs.2021.119883 34390724
     [Google Scholar]
  80. IbraheemS.N. Al-ShakarchiM.A. Effect of Antibiotics on the Pathogenic Bacteria (K. Pneumonia and P. Aeruginosa) Isolated Around the Dental Implant Area.J. Res. Appl. Sci. Biotechnol.2023215716610.55544/jrasb.2.1.22
     [Google Scholar]
  81. OlademehinO.P. KimS.J. ShufordK.L. Molecular dynamics simulation of atomic interactions in the vancomycin binding site.ACS Omega20216177578510.1021/acsomega.0c05353 33458529
     [Google Scholar]
  82. ShanL. WenlingQ. MauroP. StefanoB. Antibacterial agents targeting the bacterial cell wall.Curr. Med. Chem.202027172902292610.2174/0929867327666200128103653 32003656
     [Google Scholar]
  83. LilicM. ChenJ. BoyaciH. BraffmanN. HubinE.A. HerrmannJ. MüllerR. MooneyR. LandickR. DarstS.A. CampbellE.A. The antibiotic sorangicin A inhibits promoter DNA unwinding in a Mycobacterium tuberculosis rifampicin-resistant RNA polymerase.Proc. Natl. Acad. Sci. USA202011748304233043210.1073/pnas.2013706117 33199626
     [Google Scholar]
  84. EsberardM. Regulatory RNAs and Adaptation to Antibiotics in Staphylococcus Aureus: Example of 6S RNA and Rifampicin Susceptibility.2022
     [Google Scholar]
  85. Gil-GilT. CoronaF. MartínezJ.L. BernardiniA. The inactivation of enzymes belonging to the central carbon metabolism is a novel mechanism of developing antibiotic resistance.mSystems20205310.1128/msystems.00282-2010.1128/msystems.00282‑20 32487742
     [Google Scholar]
  86. TaguchiA. NakashimaR. NishinoK. Functional and structural characterization of Streptococcus pneumoniae pyruvate kinase involved in fosfomycin resistance.J. Biol. Chem.2023299710489210.1016/j.jbc.2023.104892 37286036
     [Google Scholar]
  87. Miklasińska-MajdanikM. Mechanisms of resistance to macrolide antibiotics among Staphylococcus aureus.Antibiotics20211011140610.3390/antibiotics10111406 34827344
     [Google Scholar]
  88. Ayoub MoubareckC. Polymyxins and bacterial membranes: A review of antibacterial activity and mechanisms of resistance.Membranes202010818110.3390/membranes10080181 32784516
     [Google Scholar]
  89. MohapatraS.S. DwibedyS.K. PadhyI. Polymyxins, the last-resort antibiotics: Mode of action, resistance emergence, and potential solutions.J. Biosci.20214638510.1007/s12038‑021‑00209‑8 34475315
     [Google Scholar]
  90. MancusoG. MidiriA. GeraceE. BiondoC. Bacterial antibiotic resistance: The most critical pathogens.Pathogens20211010131010.3390/pathogens10101310 34684258
     [Google Scholar]
  91. LeãoC. SimõesM. BorgesA. Marine phenolics: Classes, antibacterial properties, and applications.Marine Phenolic Compounds.Elsevier202337139210.1016/B978‑0‑12‑823589‑8.00013‑3
     [Google Scholar]
  92. ThawabtehA.M. SwailehZ. AmmarM. JaghamaW. YousefM. KaramanR. A BufoS. ScranoL. Antifungal and antibacterial activities of isolated marine compounds.Toxins20231529310.3390/toxins15020093 36828408
     [Google Scholar]
  93. BaqueroF. MartínezJ.L. F LanzaV. Rodríguez-BeltránJ. GalánJ.C. San MillánA. CantónR. CoqueT.M. Evolutionary pathways and trajectories in antibiotic resistance.Clin. Microbiol. Rev.2021344e000501910.1128/CMR.00050‑19 34190572
     [Google Scholar]
  94. KundarR. GokarnK. CRISPR-Cas system: A tool to eliminate drug-resistant gram-negative bacteria.Pharmaceuticals20221512149810.3390/ph15121498 36558949
     [Google Scholar]
  95. VandeplasscheE. TavernierS. CoenyeT. CrabbéA. Influence of the lung microbiome on antibiotic susceptibility of cystic fibrosis pathogens.Eur. Respir. Rev.20192815219004110.1183/16000617.0041‑2019 31285289
     [Google Scholar]
  96. LungganiA.T. DarmantoY.S. RadjasaO.K. SabdonoA. Prospective source of antimicrobial compounds from pigment produced by bacteria associated with Brown Alga (Phaeophyceae) isolated from karimunjawa island, Indonesia.IOP Conf. Ser. Earth Environ. Sci.201811601208810.1088/1755‑1315/116/1/012088
     [Google Scholar]
  97. SidinR.S. RetnaningrumE. Antibacterial activity of carotenoid pigments produced by heterotrophic bacteria from seawater in Krakal Coastal Area, Yogyakarta, Indonesia.Squalen Bull. Mar. Fish. Postharv. Biotechnol.2022172748410.15578/squalen.648
     [Google Scholar]
  98. WillemsT. De MolM.L. De BruyckerA. De MaeseneireS.L. SoetaertW.K. Alkaloids from Marine Fungi: Promising antimicrobials.Antibiotics20209634010.3390/antibiotics9060340 32570899
     [Google Scholar]
  99. RiuF. RudaA. IbbaR. SestitoS. LupinuI. PirasS. WidmalmG. CartaA. Antibiotics and carbohydrate-containing drugs targeting bacterial cell envelopes: An overview.Pharmaceuticals202215894210.3390/ph15080942 36015090
     [Google Scholar]
  100. SetiyonoE. AdhiwibawaM.A.S. IndrawatiR. PrihastyantiM.N.U. ShioiY. BrotosudarmoT.H.P. An Indonesian marine bacterium, Pseudoalteromonas rubra, produces antimicrobial prodiginine pigments.ACS Omega2020594626463510.1021/acsomega.9b04322 32175509
     [Google Scholar]
  101. AndresA.I. PetronM.J. LopezA.M. TimonM.L. Optimization of extraction conditions to improve phenolic content and in vitro antioxidant activity in craft brewers’ spent grain using response surface methodology (RSM).Foods2020910139810.3390/foods9101398 33023120
     [Google Scholar]
  102. BakhaidarR.B. NaveenN.R. BasimP. MurshidS.S. KurakulaM. AlamoudiA.J. BukharyD.M. JaliA.M. MajrashiM.A. AlshehriS. AlissaM. AhmedR.A. Response surface methodology (RSM) powered formulation development, optimization and evaluation of thiolated based mucoadhesive nanocrystals for local delivery of simvastatin.Polymers20221423518410.3390/polym14235184 36501579
     [Google Scholar]
  103. JaswirI. NoviendriD. TaherM. MohamedF. OctaviantiF. LestariW. MuktiA.G. NirwandarS. Hamad AlmansoriB.B. Optimization and formulation of fucoxanthin-loaded microsphere (F-LM) using response surface methodology (RSM) and analysis of its fucoxanthin release profile.Molecules201924594710.3390/molecules24050947 30866561
     [Google Scholar]
  104. TahraouiH. BelhadjA.E. TrikiZ. BoudellalN.R. SederS. AmraneA. ZhangJ. MoulaN. TifouraA. FerhatR. BousselmaA. MihoubiN. Mixed coagulant-flocculant optimization for pharmaceutical effluent pretreatment using response surface methodology and Gaussian process regression.Process Saf. Environ. Prot.202316990992710.1016/j.psep.2022.11.045
     [Google Scholar]
  105. TirandL. BastogneT. BechetD. LinderM. ThomasN. FrochotC. GuilleminF. Barberi-HeyobM. Response surface methodology: An extensive potential to optimize in vivo photodynamic therapy conditions.Int. J. Radiat. Oncol. Biol. Phys.200975244252
     [Google Scholar]
/content/journals/ctmc/10.2174/0115680266333406250126033304
Loading
Innovative Therapies: A Major Breakthrough in Combating Multi-Drug-resistant Bacterial Infections Using Mixture Design and Multi-Objective Optimization with NSGA-II Algorithm
Curr. Top. Med. Chem. 25, 2114 (2025); https://doi.org/10.2174/0115680266333406250126033304
/content/journals/ctmc/10.2174/0115680266333406250126033304
/content/journals/ctmc/10.2174/0115680266333406250126033304
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): Antibiotic resistance; innovative therapies; marine metabolites; multi-objective optimization; synergistic interactions

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test