Những hiểu biết về các phương pháp gần đây trong chiến lược khám phá thuốc và các mục tiêu thuốc chưa được khai thác chống lại tình trạng kháng thuốc

Gerard D (2016) Antibiotic adjuvants: rescuing antibiotics from resistance. Trends Microbiol 24:862–871 David B (2015) Antibiotic resistance breakers: can repurposed drugs fill the antibiotic discovery void? Nat Rev Drug Discov 14:821–832 World Health Organization (WHO) (2019) New report calls for urgent action to avert antimicrobial resistance crisis, Geneva Available at https://www.who.int/news-room/detail/29-04-2019-new-report-calls-for-urgent-action-to-avert-antimicrobial-resistance-crisis (accessed April 29 2019) World Health Organization (WHO) (2018) Antimicrobial resistance, Geneva Available at https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance (accessed February 15 2018) World Health Organization (WHO) (2016) Global tuberculosis report 2016. Available at www.who.int/tb/publications/global_report (accessed April 19 2019). Prasad R, Goffeau A (2012) Yeast ATP-binding cassette transporters conferring multidrug resistance. Annu. Rev. Microbiol. 66:39–63 General Assembly of the United Nations (2016) High-level meeting on antimicrobial resistance. Available at http://www.un.org/pga/71/event-latest/high-level-meeting-on-antimicrobial-resistance (accessed July 21 2019). Arzanlou M, Chai WC, Venter H (2017) Intrinsic, adaptive and acquired antimicrobial resistance in Gram-negative bacteria. Essays Biochem 61:49–59 Konstantinos M, Wendy E, Kaman GE, Mara S, John PH (2018) Challenges in identifying antibiotic resistance targets for point-of-care diagnostics in general practice. Future Microbiol 13:1157–1164 Center for Disease Control and Prevention (2019) Antibiotic resistance threats in the United States. Department of Health and Human Services, United States Available at https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf (accessed August 12 2019) Zahreddine H, Borden KL (2013) Mechanisms and insights into drug resistance in cancer. Front Pharmacol 4:1–8 Elizabeth P, Parjit K (2018) Antibiotic resistance mechanisms in bacteria: relationships between resistance determinants of antibiotic producers, environmental bacteria, and clinical pathogens. Front Microbiol 30:1–21 Lia DA, Rosella C, Giovanni S, Emanuele P, Antonio S, Migliori GB (2015) New anti-tuberculosis drugs and regimens. ERJ Open Res 1:1–15 Voniatis C, Migliori GB (2014) M. tuberculosis elimination: dream or reality? The case of Cyprus. EUR Respir J 44:543–546 Charles DW, Rajesh G, Norbet H (2015) Long-term mortality assessment of multidrug-resistant tuberculosis patients treated with delamanid. EUR Respir J 45:1498–1501 Diacon AH, Donald PR, Pym A, Grobusch M, Patentia RF, Mahanyele R, Bantubani N, Narasimooloo R, De Marez T, Heeswijk RV, Lounis N, Meyvisch P, Andries K, McNeeley DF (2012) Randomized pilot trial of eight weeks of bedaquiline (TMC207) treatment for multidrug-resistant tuberculosis: long term outcome, tolerability, and effect on emergence of drug resistance. Antimicrob Agents Chemother 56:3271–3276 Andréanne L, Caroline SF, Svetlana S, Anthony VJ, Piton NM, Andrej B, Dirk AL, Adrie JCS, Kevin P, Vadim AM (2020) New 2-Ethylthio-4-methylaminoquinazoline derivatives inhibiting two subunits of cytochrome bc1 in Mycobacterium tuberculosis. PLOS Pathog 16:1–19 Falzon D, Gandhi N, Migliori GB, Sotgiu G, Cox HS, Holtz TH, Hollm DMG, Keshavjee S, DeRiemer K, Centis R, Dambrosio L, Lange CG, Bauer M, Menzies D (2013) Collaborative group for meta-analysis of individual patient data in MDR-TB. Resistance to fluoroquinolones and second-line injectable drugs: impact on multidrug-resistant TB outcomes. EUR Respir J 42:156–168 Zumla AI, Schito M, Maeurer M (2014) Advancing the portfolio of tuberculosis diagnostics, drugs, biomarkers, and vaccines. Lancet Infect Dis 14:7–9 Arora G, Tiwari P, Mandal RS, Gupta A, Sharma D, Saha S, Singh R (2014) High throughput screen identifies small molecule inhibitors specific for Mycobacterium tuberculosis phosphoserine phosphatase. J Biol Chem 289:25149–25165 Shum KT, Lui ELH, Wong SCK, Yeung P, Sam L (2011) Aptamer-mediated inhibition of Mycobacterium tuberculosis polyphosphate kinase 2. Biochemistry 50:3261–3271 Brown GD, Denning DW, Gow NAR, Levitz SM, Netea MG, White TC (2012) Hidden killers: human fungal infections. Sci Transl Med 4:1–9 Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB (2019) Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 39:309–317 Kontoyiannis DP, Marr KA, Park BJ, Alexander BD, Anaissie EJ, Walsh TJ (2010) Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001-2006: overview of the transplant-associated infection surveillance network (TRANSNET) database. Clin Infect Dis 50:1091–1100 Gaur M, Puri N, Manoharlal R, Rai V, Mukhopadhayay G, Choudhury D, Prasad R (2008) MFS transportome of the human pathogenic yeast Candida albicans. BMC Genom 9:1–12 Paulsen IT, Sliwinski MK, Nelissen B, Goffeau A, Saier MH (1998) Unified inventory of established and putative transporters encoded within the complete genome of Saccharomyces cerevisiae. FEBS Lett 430:116–125 Gbelska Y, Krijger JJ, Breunig KD (2006) Evolution of gene families: the multidrug resistance transporter genes in five related yeast species. FEMS Yeast Res. 6:345–355 Kelly S, Lamb D, Corran A, Baldwin B, Kelly D (1995) Mode of action and resistance to azole antifungals associated with the formation of 14alpha-methylergosta-8, 24(28)-dien-3ß,6a-diol. Biochem Biophys Res Commun 207:910–915 Eddouzi J, Parker JE, Vale-Silva LA, Coste A, Ischer F, Kelly S (2013) Molecular mechanisms of drug resistance in clinical Candida species isolated from Tunisian hospitals. Antimicrob Agents Chemother 57:3182–3193 Martel CM, Parker JE, Bader O, Weig M, Gross U, Warrilow AGS (2010) Identification and characterization of four azole-resistant erg3 mutants of Candida albicans. Antimicrob Agents Chemother 54:4527–4533 Chau AS, Gurnani M, Hawkinson R, Laverdiere M, Cacciapuoti A, McNicholas PM (2005) Inactivation of sterol delta5, 6-desaturase attenuates virulence in Candida albicans. Antimicrob Agents Chemother 49:3646–3651 Morio F, Pagniez F, Lacroix C, Miegeville M, Le Pape P (2012) Amino acid substitutions in the Candida albicans sterol Δ5,6-desaturase (Erg3p) confer azole resistance: characterization of two novel mutants with impaired virulence. J Antimicrob Chemother 67:2131–2138 Korenromp EL, Williams BG, Gouws E, Dye C, Snow RW (2003) Measurement of trends in childhood malaria mortality in Africa: an assessment of progress toward targets based on verbal autopsy. Lancet Infect Dis 3:349–358 Marsh K (1998) Malaria disaster in Africa. Lancet 352:924–925 Nosten F (2000) Effects of artesunate-mefloquine combination on incidence of Plasmodium falciparum malaria and mefloquine resistance in western Thailand: a prospective study. Lancet 356:297–302 Plowe CV (2003) Monitoring antimalarial drug resistance: making the most of the tools at hand. J. Exp. Biol. 206:3745–3752 Mehta K, Fok JY (2009) Targeting transglutaminase-2 to overcome chemo-resistance in cancer cells. Drug Resistance in Cancer Cells, 1st edn. Springer-Verlag, New York, pp 95–114 Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG (2013) Cancer drug resistance: an evolving paradigm. Nat Rev Cancer 13:714–726 World Health Organization (WHO) (2018) Responding to antimalarial drug resistance, Geneva Available at https://www.who.int/malaria/areas/drug_resistance/overview/en/ (accessed April 20 2018) Hernandez RC, Jacome R, Vidal YL, Ponce de Leon S (2017) Are RNA Viruses Candidate Agents for the Next Global Pandemic? A Review. ILAR J 58:343–358. https://doi.org/10.1093/ilar/ilx026 Simmonds P (2004) Genetic diversity and evolution of hepatitis C virus - 15 years on. J Gen Virol 85:3173–3178 Chen R, Holmes EC (2010) Hitchhiking and the population genetic structure of avian influenza virus. J Mol Evol 70:98–105 Andrei G (2013) Heterogeneity and evolution of thymidine kinase and DNA polymerase mutants of herpes simplex virus type 1: Implications for Antiviral Therapy. JID 207:295–305 Renzette N, Daniel RC, Konstantin BZ, Ping L, Glen RG, Daniel A, Alyssa JP, Evelyn AK, Daniel NB, Yu-Ping PJ, Jensen D, Celia AS, Timothy FK, Robert WF, Jennifer PW (2014) Evolution of the influenza A virus genome during development of oseltamivir resisitance in vitro. J Virol 88:272–281 Gott M (2017) The distinct contributions of fitness and genetic barrier to the development of antiviral drug resistance. Curr Opin Virol 2:644–650 Bang KB, Kim HJ (2014) Management of antiviral drug resistance in chronic hepatitis B. World J Gastroenterol 20:11641–11646 Andrew RJ, Jennifer LR, Aprilfawn W, Robert E, Andrei O, Tomoya B, Hirotada M, Scott AL, Bernhard P, Sanjay A (2006) Experimental and computational assessment of conditionally essential genes in Escherichia coli. J Bacteriol 188:8259–8271 Delia MA, Millar KE, Bhavsar AP, Tomljenovic AM, Hutter B, Schaab C, Moreno HG, Brown ED (2009) Probing teichoic acid genetics with bioactive molecules reveals new interactions among diverse processes in bacterial cell wall biogenesis. Chem Biol 16:548–556 Autret N, Charbit A (2005) Lessons from signature-tagged mutagenesis on the infectious mechanisms of pathogenic bacteria. FEMS Microbiology Reviews. 29:703–717 Hensel M, Shea JE, Gleeson C, Jones MD, Dalton E (1995) Simultaneous identification of bacterial virulence genes by negative selection. Science 269:400–403 Nichols RJ, Sen S, Choo YJ, Beltrao P, Zietek M, Chaba R, Lee S, Kazmierczak KM, Lee KJ, Wong A, Shales M, Lovett S, Winkler ME, Krogan NJ, Typas A, Gross CA (2011) Phenotypic landscape of a bacterial cell. Cell. 144:143–156 Opijnen VT, Camilli A (2013) Transposon insertion sequencing: a new tool for systems-level analysis of microorganisms. Nat Rev Microbiol 11:435–442 Turner KH, Wessel AK, Palmer GC, Murray JL, Whiteley M (2015) Essential genome of Pseudomonas aeruginosa in cystic fibrosis sputum. Proc Natl Acad Sci U S A 112:4110–4115 Haas H (2014) Fungal siderophore metabolism with a focus on Aspergillus fumigatus. Natural. Product Reports. 31:1266–1276 Huh WK, Kim ST, Kim H, Jeong G, Kang SO (2001) Deficiency of D-erythroascorbic acid attenuates hyphal growth and virulence of Candida albicans. Infection and Immunity 69:3939–3946 Paul D, Chatterjee A, Begley TP, Ealick SE (2010) Domain organization in Candida glabrata THI6, a bifunctional enzyme required for thiamin biosynthesis in eukaryotes. Biochemistry 49:9922–9934 Fahnoe KC, Mark EF, Glenn G, Veerabahu S, Che Y, Andrew PT (2012) Non-traditional antibacterial screening approaches for the identification of novel inhibitors of the glyoxylate shunt in Gram-negative pathogens. PLoS One 7:1–7 Zlitni S, Ferruccio LF, Brown ED (2013) Metabolic suppression identifies new antibacterial inhibitors under nutrient limitation. Nat Chem Biol. 9:796–804 Starkey M (2014) Identification of anti-virulence compounds that disrupt quorum-sensing regulated acute and persistent pathogenicity. PLoS Pathogen 10:1–18 Pethe K, Bifani P, Jang J, Kang S, Park S, Ahn S, Jiricek J, Jung J, Jeon HK, Cechetto J, Christophe T, Lee H, Kempf MP (2013) Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis. Nat Med 19:1157–1160 Delia MA, Pereira BMP (2009) Are essential genes really essential? Trends Microbiol 17:433–438 Liu A, Tran L, Becket E, Lee K, Chinn L, Park E, Tran K, Miller JH (2010) Antibiotic sensitivity profiles determined with an Escherichia coli gene knockout collection: generating an antibiotic bar code. Antimicrobial Agents and Chemotherapy. 54:1393–1403 El-Ghachi M, Bouhss A, Blanot D, Mengin-Lecreulx D (2004) The bacA gene of Escherichia coli encodes an undecaprenyl pyrophosphate phosphatase activity. J Biol Chem 279:30106–30113 Pathania R, Zlitni S, Barker C, Das R, Gerritsma DA, Lebert J, Awuah E, Melacini G, Capretta FA, Brown ED (2009) Chemical genomics in Escherichia coli identifies an inhibitor of bacterial lipoprotein targeting. Nature Chemical Biology. 5:849–856 Taylor PL, Rossi L, De Pascale G, Wright GD (2012) A forward chemical screen identifies antibiotic adjuvants in Escherichia coli. ACS Chem Biol 7:1547–1555 Laaveri T, Sterne J, Rombo L, Kantele A (2016) Systematic review of loperamide: No proof of antibiotics being superior to loperamide in treatment of mild/moderate travellers' diarrhoea. Travel Med Infect Dis. 14:299–312 Borisy AA, Peter JE, Nicole WH, Margaret SL, Joseph L, Roydon EP, Serbedzija G, Zimmermann GR, Michael AF, Brent RS, Curtis TK (2003) Systematic discovery of multicomponent therapeutics. Proc Natl Acad Sci U S A 100:7977–7982 King AM, Reid-Yu SA, Wang W, King DT, De Pascale G, Strynadka NC, Walsh TR, Coombes BK, Wright GD (2014) Aspergillomarasmine A overcomes metallo-β-lactamase antibiotic resistance. Nature. 510:503–506 Ejim L, Farha MA, Falconer SB, Wildenhain J, Coombes BK, Tyers M (2011) Combinations of antibiotics and non-antibiotic drugs enhance antimicrobial efficacy. Nat Chem Biol 7:348–350 Crick C (1970) Central dogma of molecular biology. Nature 227:561–563 Khaledi A, Schniederjans M, Pohl S, Rainer R, Bodenhofer U, Xia B, Klawonn F, Bruchmann S, Preusse M, Eckweiler D, Dotsch A, Haussler S (2016) Transcriptome profiling of antimicrobial resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 60:4722–4733 Michael RH, Heidi A (2018) Can light-based approaches overcome antimicrobial resistance? Drug Dev. Res 80:48–67 Maria GFC, Bernegossi J, Marise de Freitas L, Fontana CR, Chorilli M (2016) Nanotechnology-based drug delivery systems for photodynamic therapy of cancer: a review. Molecules 21:342. https://doi.org/10.3390/molecules21030342 Amram M (2000) Peptide-based antibiotics: a potential answer to raging antimicrobial resistance. Drug Dev Res 50:440–447 Lei J, Lichun S, Huang S, Chenhong Z, Li P, He J, Vienna M, David HC, He Q (2019) The antimicrobial peptides and their potential clinical applications. Am J Transl Res 11:3919–3931 Hye Been K, Jiwon S (2019) Antimicrobial peptides under clinical investigation. Peptide Sci:e24122. https://doi.org/10.1002/pep2.24122 John PP, Libertad GV, Yin Z, Ohad LE, Anthony ZW, Jingjing L, Jun X, Qian M, Devon MF, Julia B, Robert HA, Christophe HD (2019) Gamblers: an antibiotic-induced evolvable cell subpopulation differentiated by reactive-oxygen-induced general stress response. Mol Cell 74:785–800 Pedro VB, Matthew PM, Andreia C, Ferreira AD, Niamh MM, Marta M, Alexandra RF (2018) Nano-strategies to fight multidrug resistant bacteria - a battle of the titans. Front Microbiol 9:1441–1453 Tianyuan S, Qiuxia W, Zhen W, Gong Z, Xuesong S, Qing YH (2019) Photocatalytic protein damage by silver nanoparticles circumvents bacterial stress response and multidrug resistance. Physiol Mol Biol Plants 4:1–12 Liuliu Z, Huayun Z, Yu G, Xiaohua W, Pingping W (2019) Dual drug-loaded PLA nanoparticles bypassing drug resistance for improved leukemia therapy. J Nanopart Res 21:83–88 Bao W, Liu R, Wang Y (2015) PLGA-PLL-PEG-Tf-based targeted nanoparticles drug delivery system enhance antitumor efficacy via intrinsic apoptosis pathway. Int J Nanomed 10:557–566 Sinha R, Kim GJ, Nie S, Shin DM (2006) Nanotechnology in cancer therapeutics: bioconjugated nanoparticles for drug delivery. Mol. Cancer Ther. 5:1909–1917 Chuang YM, Belchis DA, Karakousis PC (2013) The polyphosphate kinase gene ppk2 is required for Mycobacterium tuberculosis inorganic polyphosphate regulation and virulence. Microbiology 4:1–9 Chuang M, Nirmalya B, Dalin R, Harvey R, Joel SB, Petros CK (2015) Deficiency of the novel exopolyphosphatase Rv1026/PPX2 leads to metabolic downshift and altered cell wall permeability in Mycobacterium tuberculosis. Microbiol 6:1–15 FatmaAbdelaziz A, Mohamed El-Behedy E, Heba Ali M (2008) New targets for antibacterial agents. Biotechnol Mol Biol Rev 3:46–57 Balcewich MD, Stubbs KA, He Y, James TW, Davies GJ, Vocadlo DJ, Mark BL (2009) Insight into a strategy for attenuating AmpC-mediated beta-lactam resistance: structural basis for selective inhibition of the glycoside hydrolase NagZ. Protein Science. 18:1541–1551 Boudreau MA, Fisher JF, Mobashery S (2012) Messenger functions of the bacterial cell wall-derived muropeptides. Biochemistry. 51:2974–2990 Yi-Wei H, Rouh-Mei H, Cheng-Wen L, Tung-Ching C, Tsuey-Ching Y (2012) NagZ-Dependent and NagZ-independent mechanisms for β-lactamase expression in Stenotrophomonas maltophilia. Antimicrob Agents Chemother 56:1936–1941 Grishma V, Stubbs KA, Jerome D, Bleriot Y, David JV, Brian LM (2017) Conformational flexibility of the glycosidase NagZ allows it to bind structurally diverse inhibitors to suppress β-lactam antibiotic resistance. Protein Sci 26:1161–1170. https://doi.org/10.1002/pro.3166 Korfmann G, Sanders CC (1989) AmpG is essential for high-level expression of AmpC β- lactamase in Enterobacter cloacae. Antimicrob Agents Chemother 33:1946–1951 Mark BL, Vocadlo DJ, Oliver A (2011) Providing β-lactams a helping hand: Targeting the AmpC β-lactamase induction pathway. Future Microbiol 6:1415–1427 Nocek B, Kochinyan S, Proudfoot M, Brown G, Evdokimova E, Osipiuk J, Edwards AM, Savchenko A, Joachimiak A, Yakuninm F (2008) Polyphosphate-dependent synthesis of ATP and ADP by the family-2 polyphosphate kinases in bacteria. Proc Natl Acad Sci U S A 105:17730–17735 Singh M, Tiwari P, Arora G, Agarwal S, Kidwai S, Singh R (2016) Establishing virulence associated polyphosphate kinase 2 as a drug target for Mycobacterium tuberculosis. Sci Rep 6:1–13 Singh R, Singh M, Arora G, Kumar S, Tiwari P, Kidwai S (2013) Polyphosphate deficiency in Mycobacterium tuberculosis is associated with enhanced drug susceptibility and impaired growth in guinea pigs. J Bacteriol 195:2839–2851 Zhang H, Ishige K, Kornberg A (2002) A polyphosphate kinase (PPK2) widely conserved in bacteria. Proc Natl Acad Sci U S A 99:16678–16683 Arkadiusz B, Robert E, Artur O (2018) Functional flexibility of electron flow between quinol oxidation Qo site of cytochrome bc1 and cytochrome c revealed by combinatory effects of mutations in cytochrome b, iron-sulfur protein and cytochrome c1. Biochimica et Biophysica Acta Bioenergetics 1859:754–761 Jan R, Anthony V, Claudia S, Philippe B, Florence P, Andrej B, Stewart TC (2015) Lansoprazole is an antituberculous prodrug targeting cytochrome bc1. Nat Commun 6:7659 Dominic B, Wei-Chun K, Carola H (2014) Structural analysis of atovaquone-inhibited cytochrome bc1 complex reveals the molecular basis of antimalarial drug action. Nat Commun 5:4029 Michael WM, Elisabeth D, Maria Valkova V, Jason WC, Michael TM, Fevzi D, Akhil BV (2005) Uncovering the molecular mode of action of the antimalarial drug atovaquone using a bacterial system. J Biol Chem 280:27458–27465 Li-shar H, David C, Eric YT, Edward AB (2005) Binding of the respiratory chain inhibitor antimycin to the mitochondrial bc1 complex: a new crystal structure reveals an altered intramolecular hydrogen-bonding pattern. J Mol Biol 351:573–597 Georg T, Brigitte K, Hans R, Gerhard H (1984) The mode of action of stigmatellin, a new inhibitor of the cytochrome bcl segment of the respiratory chain. Biochimica et Biophysica Acta 765:227–235 Steven W, Meinhardt A (1982) R. Crofts. The site and mechanism of action of myxothiazol as an inhibitor of electron transfer in Rhodopseudomonas sphaeroides. FEBS Lett 149:217–222 Burkhard AH, Martin S (2015) Core principles of bacterial autoinducer systems. Microbiol Mol Biol Rev 79:153–169 Decho AW, Visscher PT, Ferry J, Kawaguchi T, He L, Przekop KM, Norma RS, Reid RP (2009) Autoinducers extracted from microbial matsreveal a surprising diversity of N-acylhomoserine lactones (AHLs) and abundance changes that may relate to diel pH. Environ Microbiol 11:409–420 Hentzer M, Wu H, Andersen JB, Riedel K, Rasmussen TB, Bagge N, Kumar N, Schembri MA, Song ZJ, Kristoffersen P, Manefield M, Costerton JW, Molin S, Eberl L, Steinberg P, Kjelleberg S, Hoiby N, Givskov M (2003) Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J 22:3803–3815 Brynildsen MP, Winkler JA, Spina CS, Macdonald IC, Collins JJ (2013) Potentiating antibacterial activity by predictably enhancing endogenous microbial ROS production. Nat. Biotechnol. 31:160–165 Rajni K, Shashikant R (2019) In bacterial cell division machinery: an insight for development of new antibacterial agent. In: Kumar S, Egbuna C (eds) Phytochemistry: An in-silico and in-vitro Update. Springer Nature, pp 109–132 Rohmer M, Grosdemange BC, Seemann M, Tritsch D (2004) Isoprenoid biosynthesis as a novel target for antibacterial and antiparasitic drugs. Curr Opin Investigational New Drugs 5:154–162 Kuntz L, Tritsch D, Grosdemange BC, Hemmerlin A, Willem A, Bach TJ, Rohmer M (2005) Isoprenoid biosynthesis as a target for antibacterial and antiparasitic drugs: phosphonohydroxamic acids as inhibitors of deoxyxylulose phosphate reducto-isomerase. Biochem J 386:127–135 Izard TA (2002) The crystal structures of phosphopantetheineadenylyltransferase with bound substrates reveal the enzyme's catalytic mechanism. J Mol Biol 315:487–495 Izard TA (2003) Novel adenylate binding site confers phosphopantetheineadenylyltransferase interactions with Coenzyme. J Bacteriol 185:4074–4080 Marko Juki C, Stanislav G, Matej S (2019) Reaching toward underexplored targets in antibacterial. Drug Dev Res 80:6–10 Elif T, Cynthia W, Tina MK, Singh N, Mauricio CL, Robert D, Van MS, Pamela JY (2018) Prevalence and patterns of higher-order drug interactions in Escherichia coli. npj Syst Biol Appl 4:31