Abstract: Adenosine triphosphate (ATP)-binding cassette (ABC) transporter systems are divided into importers and exporters that facilitate the movement of diverse substrate molecules across the lipid bilayer, against the concentration gradient. These transporters comprise two highly conserved nucleotide-binding domains (NBDs) and two transmembrane domains (TMDs). Unlike ABC exporters, prokaryotic ABC importers require an additional substrate-binding protein (SBP) as a recognition site for specific substrate translocation. The discovery of a large number of ABC systems in bacterial pathogens revealed that these transporters are crucial for the establishment of bacterial infections. The existing literature has highlighted the roles of ABC transporters in bacterial growth, pathogenesis, and virulence. These roles include importing essential nutrients required for a variety of cellular processes and exporting outer membrane-associated virulence factors and antimicrobial substances. This review outlines the general structures and classification of ABC systems to provide a comprehensive view of the activities and roles of ABC transporters associated with bacterial virulence and pathogenesis during infection.

ABC转运蛋白的结构及其在细菌致病过程中的作用

[1]AbrilAG, Quintela-BalujaM, VillaTG, et al., 2022. Proteomic characterization of virulence factors and related proteins in Enterococcus strains from dairy and fermented food products. Int J Mol Sci, 23(18):10971.

[2]AkhtarAA, TurnerDPJ, 2022. The role of bacterial ATP-binding cassette (ABC) transporters in pathogenesis and virulence: therapeutic and vaccine potential. Microb Pathog, 171:105734.

[3]AlavI, SuttonJM, RahmanKM, 2018. Role of bacterial efflux pumps in biofilm formation. J Antimicrob Chemother, 73(8):2003-2020.

[4]Alcalde-RicoM, Hernando-AmadoS, BlancoP, et al., 2016. Multidrug efflux pumps at the crossroad between antibiotic resistance and bacterial virulence. Front Microbiol, 7:1483.

[5]AllanRN, SkippP, JefferiesJ, et al., 2014. Pronounced metabolic changes in adaptation to biofilm growth by Streptococcus pneumoniae. PLoS ONE, 9(9):e107015.

[6]AllisonDG, 2003. The biofilm matrix. Biofouling, 19(2):139-150.

[7]AlteriCJ, MobleyHLT, 2012. Escherichia coli physiology and metabolism dictates adaptation to diverse host microenvironments. Curr Opin Microbiol, 15(1):3-9.

[8]AmblarM, ZaballosÁ, de la CampaAG, 2022. Role of PatAB transporter in efflux of levofloxacin in Streptococcus pneumoniae. Antibiotics, 11(12):1837.

[9]AnteloGT, VilaAJ, GiedrocDP, et al., 2021. Molecular evolution of transition metal bioavailability at the host-pathogen interface. Trends Microbiol, 29(5):441-457.

[10]BaylayAJ, PiddockLJV, 2015. Clinically relevant fluoroquinolone resistance due to constitutive overexpression of the PatAB ABC transporter in Streptococcus pneumoniae is conferred by disruption of a transcriptional attenuator. J Antimicrob Chemother, 70(3):670-679.

[11]BeceiroA, TomásM, BouG, 2013. Antimicrobial resistance and virulence: a successful or deleterious association in the bacterial world?Clin Microbiol Rev, 26(2):185-230.

[12]BeggSL, 2019. The role of metal ions in the virulence and viability of bacterial pathogens. Biochem Soc Trans, 47(1):77-87.

[13]BeisK, 2015. Structural basis for the mechanism of ABC transporters. Biochem Soc Trans, 43(5):889-893.

[14]BerntssonRPA, SmitsSHJ, SchmittL, et al., 2010. A structural classification of substrate-binding proteins. FEBS Lett, 584(12):2606-2617.

[15]BiYC, MannE, WhitfieldC, et al., 2018. Architecture of a channel-forming O-antigen polysaccharide ABC transporter. Nature, 553(7688):361-365.

[16]BilsingFL, AnlaufMT, HachaniE, et al., 2023. ABC transporters in bacterial nanomachineries. Int J Mol Sci, 24(7):6227.

[17]BiondoC, 2023. Bacterial antibiotic resistance: the most critical pathogens. Pathogens, 12(1):116.

[18]BoëlG, OrelleC, JaultJM, et al., 2019. ABC systems: structural and functional variations on a common theme. Res Microbiol, 170(8):301-303.

[19]BogomolnayaLM, AndrewsKD, TalamantesM, et al., 2013. The ABC-type efflux pump MacAB protects Salmonella enterica serovar Typhimurium from oxidative stress. mBio, 4(6):e00630-13.

[20]CasadevallA, PirofskiLA, 2000. Host-pathogen interactions: basic concepts of microbial commensalism, colonization, infection, and disease. Infect Immun, 68(12):6511-6518.

[21]ChenL, HouWT, FanT, et al., 2020. Cryo-electron microscopy structure and transport mechanism of a wall teichoic acid ABC transporter. mBio, 11(2):e02749-19.

[22]ChoiCC, FordRC, 2021. ATP binding cassette importers in eukaryotic organisms. Biol Rev, 96(4):1318-1330.

[23]CrowA, GreeneNP, KaplanE, et al., 2017. Structure and mechanotransmission mechanism of the MacB ABC transporter superfamily. Proc Natl Acad Sci USA, 114(47):12572-12577.

[24]CuiLQ, WangXR, HuangDY, et al., 2020. CRISPR-cas3 of Salmonella upregulates bacterial biofilm formation and virulence to host cells by targeting quorum-sensing systems. Pathogens, 9:53.

[25]CuthbertsonL, KosV, WhitfieldC, 2010. ABC transporters involved in export of cell surface glycoconjugates. Microbiol Mol Biol Rev, 74(3):341-362.

[26]DavidsonAL, ChenJ, 2004. ATP-binding cassette transporters in bacteria. Annu Rev Biochem, 73:241-268.

[27]DavidsonAL, DassaE, OrelleC, et al., 2008. Structure, function, and evolution of bacterial ATP-binding cassette systems. Microbiol Mol Biol Rev, 72(2):317-364.

[28]DawsonRJP, LocherKP, 2007. Structure of the multidrug ABC transporter Sav1866 from Staphylococcus aureus in complex with AMP-PNP. FEBS Lett, 581(5):935-938.

[29]de BoerM, GouridisG, VietrovR, et al., 2019. Conformational and dynamic plasticity in substrate-binding proteins underlies selective transport in ABC importers. eLife, 8:e44652.

[30]de la Torre LI, Vergara MezaJG, CabarcaS, et al., 2021. Comparison of carbohydrate ABC importers from Mycobacterium tuberculosis. BMC Genomics, 22:841.

[31]DelepelaireP, 2019. Bacterial ABC transporters of iron containing compounds. Res Microbiol, 170(8):345-357.

[32]DelmarJA, SuCC, YuEW, 2014. Bacterial multidrug efflux transporters. Annu Rev Biophys, 43:93-117.

[33]DoerrlerWT, ReedyMC, RaetzCRH, 2001. An Escherichia coli mutant defective in lipid export. J Biol Chem, 276(15):11461-11464.

[34]DongHH, ZhangZY, TangXD, et al., 2017. Structural and functional insights into the lipopolysaccharide ABC transporter LptB₂FG. Nat Commun, 8:222.

[35]DuXJ, WangF, LuXN, et al., 2012. Biochemical and genetic characteristics of Cronobacter sakazakii biofilm formation. Res Microbiol, 163(6-7):448-456.

[36]EitingerT, RodionovDA, GroteM, et al., 2011. Canonical and ECF-type ATP-binding cassette importers in prokaryotes: diversity in modular organization and cellular functions. FEMS Microbiol Rev, 35(1):3-67.

[37]el GarchF, LismondA, PiddockLJV, et al., 2010. Fluoroquinolones induce the expression of patA and patB, which encode ABC efflux pumps in Streptococcus pneumoniae. J Antimicrob Chemother, 65(10):2076-2082.

[38]FahmyA, SrinivasanA, WebberMA, 2016. The relationship between bacterial multidrug efflux pumps and biofilm formation. In: Li XZ, Elkins CA, Zgurskaya HI (Eds.), Efflux-Mediated Antimicrobial Resistance in Bacteria. Adis, Cham, p.651-663.

[39]FanCC, KaiserJT, ReesDC, 2020. A structural framework for unidirectional transport by a bacterial ABC exporter. Proc Natl Acad Sci USA, 117(32):19228-19236.

[40]FiorentinoF, BollaJR, MehmoodS, et al., 2019. The different effects of substrates and nucleotides on the complex formation of ABC transporters. Structure, 27(4):651-659.e3.

[41]FordRC, BeisK, 2019. Learning the ABCs one at a time: structure and mechanism of ABC transporters. Biochem Soc Trans, 47(1):23-36.

[42]FordRC, HellmichUA, 2020. What monomeric nucleotide binding domains can teach us about dimeric ABC proteins. FEBS Lett, 594(23):3857-3875.

[43]FrançaA, GaioV, LopesN, et al., 2021. Virulence factors in coagulase-negative staphylococci. Pathogens, 10(2):170.

[44]FuTW, FanXY, LongQX, et al., 2017. Comparative analysis of prophages in Streptococcus mutans genomes. PeerJ, 5:e4057.

[45]FulyaniF, Schuurman-WoltersGK, ŽagarAV, et al., 2013. Functional diversity of tandem substrate-binding domains in ABC transporters from pathogenic bacteria. Structure, 21(10):1879-1888.

[46]GaoL, MaYY, LiXT, et al., 2020. Research on the roles of genes coding ATP‐binding cassette transporters in Porphyromonas gingivalis pathogenicity. J Cell Biochem, 121(1):93-102.

[47]GhaneiH, AbeyrathnePD, LamJS, 2007. Biochemical characterization of MsbA from Pseudomonas aeruginosa. J Biol Chem, 282(37):26939-26947.

[48]GiulianiSE, FrankAM, CorglianoDM, et al., 2011. Environment sensing and response mediated by ABC transporters. BMC Genomics, 12(S1):S8.

[49]GomesAC, MoreiraAC, MesquitaG, et al., 2018. Modulation of iron metabolism in response to infection: twists for all tastes. Pharmaceuticals, 11(3):84.

[50]GuffickC, HsiehPY, AliA, et al., 2022. Drug‐dependent inhibition of nucleotide hydrolysis in the heterodimeric ABC multidrug transporter PatAB from Streptococcus pneumoniae. FEBS J, 289(13):3770-3788.

[51]GuptaP, SarkarS, DasB, et al., 2016. Biofilm, pathogenesis and prevention—a journey to break the wall: a review. Arch Microbiol, 198(1):1-15.

[52]Hernando-AmadoS, BlancoP, Alcalde-RicoM, et al., 2016. Multidrug efflux pumps as main players in intrinsic and acquired resistance to antimicrobials. Drug Resist Updates, 28:13-27.

[53]HicksG, JiaZC, 2018. Structural basis for the lipopolysaccharide export activity of the bacterial lipopolysaccharide transport system. Int J Mol Sci, 19(9):2680.

[54]HigginsCF, LintonKJ, 2004. The ATP switch model for ABC transporters. Nat Struct Mol Biol, 11(10):918-926.

[55]HollandIB, 2019. Rise and rise of the ABC transporter families. Res Microbiol, 170(8):304-320.

[56]HonsaES, JohnsonMDL, RoschJW, 2013. The roles of transition metals in the physiology and pathogenesis of Streptococcus pneumoniae. Front Cell Infect Microbiol, 3:92.

[57]HuangLL, WuCR, GaoHJ, et al., 2022. Bacterial multidrug efflux pumps at the frontline of antimicrobial resistance: an overview. Antibiotics, 11(4):520.

[58]IlariA, PescatoriL, di SantoR, et al, 2016. Salmonella enterica serovar Typhimurium growth is inhibited by the concomitant binding of Zn(II) and a pyrrolyl-hydroxamate to ZnuA, the soluble component of the ZnuABC transporter. Biochim Biophys Acta (BBA) Gen Subj, 1860(3):534-541.

[59]ImmadisettyK, HettigeJ, MoradiM, 2019. Lipid-dependent alternating access mechanism of a bacterial multidrug ABC exporter. ACS Cent Sci, 5(1):43-56.

[60]IzoréT, Contreras-MartelC, el MortajiL, et al., 2010. Structural basis of host cell recognition by the pilus adhesin from Streptococcus pneumoniae. Structure, 18(1):106-115.

[61]JeckelmannJM, ErniB, 2020. Transporters of glucose and other carbohydrates in bacteria. Pflügers Arch Eur J Physiol, 472(9):1129-1153.

[62]JenulC, HorswillAR, 2019. Regulation of Staphylococcus aureus virulence. In: Fischetti VA, Novick RP, Ferretti JJ, et al. (Eds.), Gram-Positive Pathogens, 3rd Ed. American Society for Microbiology, Washington, p.669-686.

[63]JiangRJ, XiangMY, ChenWT, et al., 2021. Biofilm characteristics and transcriptomic analysis of Haemophilus parasuis. Vet Microbiol, 258:109073.

[64]KadabaNS, KaiserJT, JohnsonE, et al., 2008. The high-affinity E. coli methionine ABC transporter: structure and allosteric regulation. Science, 321(5886):250-253.

[65]KalitaA, HuJ, TorresAG, 2014. Recent advances in adherence and invasion of pathogenic Escherichia coli. Curr Opin Infect Dis, 27(5):459-464.

[66]KanonenbergK, SpitzO, ErenburgIN, et al., 2018. Type I secretion system—it takes three and a substrate. FEMS Microbiol Lett, 365(11):fny094.

[67]KhanF, PhamDTN, TabassumN, et al., 2020. Treatment strategies targeting persister cell formation in bacterial pathogens. Crit Rev Microbiol, 46(6):665-688.

[68]KleinRD, HultgrenSJ, 2020. Urinary tract infections: microbial pathogenesis, host‒pathogen interactions and new treatment strategies. Nat Rev Microbiol, 18(4):211-226.

[69]KolichLR, ChangYT, CoudrayN, et al., 2020. Structure of MlaFB uncovers novel mechanisms of ABC transporter regulation. eLife, 9:e60030.

[70]KonishiH, HioM, KobayashiM, et al., 2020. Bacterial chemotaxis towards polysaccharide pectin by pectin-binding protein. Sci Rep, 10:3977.

[71]LeeM, KimHL, SongS, et al., 2013. The α-barrel tip region of Escherichia coli TolC homologs of Vibrio vulnificus interacts with the MacA protein to form the functional macrolide-specific efflux pump MacAB-TolC. J Microbiol, 51(2):154-159.

[72]LeeY, SongS, ShengLL, et al., 2018. Substrate binding protein DppA1 of ABC transporter DppBCDF increases biofilm formation in Pseudomonas aeruginosa by inhibiting Pf5 prophage lysis. Front Microbiol, 9:30.

[73]LeisicoF, GodinhoLM, GonçalvesIC, et al., 2020. Multitask ATPases (NBDs) of bacterial ABC importers type I and their interspecies exchangeability. Sci Rep, 10:19564.

[74]LewinsonO, Livnat-LevanonN, 2017. Mechanism of action of ABC importers: conservation, divergence, and physiological adaptations. J Mol Biol, 429(5):606-619.

[75]LewinsonO, OrelleC, SeegerMA, 2020. Structures of ABC transporters: handle with care. FEBS Lett, 594(23):3799-3814.

[76]LewisVG, WeenMP, McDevittCA, 2012. The role of ATP-binding cassette transporters in bacterial pathogenicity. Protoplasma, 249(4):919-942.

[77]LiJ, LiuDH, DingT, 2021. Transcriptomic analysis reveal differential gene expressions of Escherichia coli O157:H7 under ultrasonic stress. Ultrason Sonochem, 71:105418.

[78]LiYY, OrlandoBJ, LiaoMF, 2019. Structural basis of lipopolysaccharide extraction by the LptB₂FGC complex. Nature, 567(7749):486-490.

[79]LinMF, LinYY, TuCC, et al., 2017. Distribution of different efflux pump genes in clinical isolates of multidrug-resistant Acinetobacter baumannii and their correlation with antimicrobial resistance. J Microbiol Immunol Infect, 50(2):224-231.

[80]LiuB, ZhengDD, ZhouSY, et al., 2022. VFDB 2022: a general classification scheme for bacterial virulence factors. Nucleic Acids Res, 50(D1):D912-D917.

[81]LiuWJ, HuangLX, SuYQ, et al., 2017. Contributions of the oligopeptide permeases in multistep of Vibrio alginolyticus pathogenesis. MicrobiologyOpen, 6(5):e00511.

[82]LocherKP, 2016. Mechanistic diversity in ATP-binding cassette (ABC) transporters. Nat Struct Mol Biol, 23(6):487-493.

[83]LocherKP, BorthsE, 2004. ABC transporter architecture and mechanism: implications from the crystal structures of BtuCD and BtuF. FEBS Lett, 564(3):264-268.

[84]LowDE, 2004. Quinolone resistance among pneumococci: therapeutic and diagnostic implications. Clin Infect Dis, 38(S4):S357-S362.

[85]LuoQS, YangX, YuS, et al., 2017. Structural basis for lipopolysaccharide extraction by ABC transporter LptB₂FG. Nat Struct Mol Biol, 24(5):469-474.

[86]MaqboolA, HorlerRSP, MullerA, et al., 2015. The substrate-binding protein in bacterial ABC transporters: dissecting roles in the evolution of substrate specificity. Biochem Soc Trans, 43(5):1011-1017.

[87]MiW, LiYY, YoonSH, et al., 2017. Structural basis of MsbA-mediated lipopolysaccharide transport. Nature, 549(7671):233-237.

[88]MiryalaSK, RamaiahS, 2019. Exploring the multi-drug resistance in Escherichia coli O157:H7 by gene interaction network: a systems biology approach. Genomics, 111(4):958-965.

[89]MitraA, KoYH, CingolaniG, et al., 2019. Heme and hemoglobin utilization by Mycobacterium tuberculosis. Nat Commun, 10:4260.

[90]MurdochCC, SkaarEP, 2022. Nutritional immunity: the battle for nutrient metals at the host‒pathogen interface. Nat Rev Microbiol, 20(11):657-670.

[91]MurphyTF, BrauerAL, JohnsonA, et al., 2016. ATP-binding cassette (ABC) transporters of the human respiratory tract pathogen, Moraxella catarrhalis: role in virulence. PLoS ONE, 11(7):e0158689.

[92]NaoeY, NakamuraN, DoiA, et al., 2016. Crystal structure of bacterial haem importer complex in the inward-facing conformation. Nat Commun, 7:13411.

[93]NevilleSL, SjöhamnJ, WattsJA, et al., 2021. The structural basis of bacterial manganese import. Sci Adv, 7(32):eabg3980.

[94]OhashiH, HasegawaM, WakimotoK, et al., 2015. Next-generation technologies for multiomics approaches including interactome sequencing. Biomed Res Int, 2015:104209.

[95]OldhamML, ChenSS, ChenJ, 2013. Structural basis for substrate specificity in the Escherichia coli maltose transport system. Proc Natl Acad Sci USA, 110(45):18132-18137.

[96]OwensTW, TaylorRJ, PahilKS, et al., 2019. Structural basis of unidirectional export of lipopolysaccharide to the cell surface. Nature, 567(7749):550-553.

[97]PaciV, KrastevaI, OrsiniM, et al., 2020. Proteomic analysis of Brucella melitensis and Brucella ovis for identification of virulence factor using bioinformatics approachs. Mol Cell Probes, 53:101581.

[98]PaludanSR, PradeuT, MastersSL, et al., 2021. Constitutive immune mechanisms: mediators of host defence and immune regulation. Nat Rev Immunol, 21(3):137-150.

[99]PatelS, MathivananN, GoyalA, 2017. Bacterial adhesins, the pathogenic weapons to trick host defense arsenal. Biomed Pharmacother, 93:763-771.

[100]PierGB, 2007. Pseudomonas aeruginosa lipopolysaccharide: a major virulence factor, initiator of inflammation and target for effective immunity. Int J Med Microbiol, 297(5):277-295.

[101]PierceyMJ, HingstonPA, Truelstrup HansenL, 2016. Genes involved in Listeria monocytogenes biofilm formation at a simulated food processing plant temperature of 15 °C. Int J Food Microbiol, 223:63-74.

[102]PietrocolaG, CampocciaD, MottaC, et al., 2022. Colonization and infection of indwelling medical devices by Staphylococcus aureus with an emphasis on orthopedic implants. Int J Mol Sci, 23(11):5958.

[103]RahmanA, AmirkhaniA, ChowdhuryD, et al., 2022. Proteome of Staphylococcus aureus biofilm changes significantly with aging. Int J Mol Sci, 23(12):6415.

[104]RempelS, StanekWK, SlotboomDJ, 2019. ECF-type ATP-binding cassette transporters. Annu Rev Biochem, 88:551-576.

[105]RibetD, CossartP, 2015. How bacterial pathogens colonize their hosts and invade deeper tissues. Microbes Infect, 17(3):173-183.

[106]RiceAJ, AlvarezFJD, SchultzKM, et al., 2013. EPR spectroscopy of MolB₂C₂-A reveals mechanism of transport for a bacterial type II molybdate importer. J Biol Chem, 288(29):21228-21235.

[107]RiceAJ, ParkA, PinkettHW, 2014. Diversity in ABC transporters: type I, II and III importers. Crit Rev Biochem Mol Biol, 49(5):426-437.

[108]Rodríguez-ArceI, Al-JubairT, EubaB, et al., 2019. Moonlighting of Haemophilus influenzae heme acquisition systems contributes to the host airway-pathogen interplay in a coordinated manner. Virulence, 10(1):315-333.

[109]RosaLT, BianconiME, ThomasGH, et al., 2018. Tripartite ATP-independent periplasmic (TRAP) transporters and tripartite tricarboxylate transporters (TTT): from uptake to pathogenicity. Front Cell Infect Microbiol, 8:33.

[110]SansonettiPJ, 1993. Bacterial pathogens, from adherence to invasion: comparative strategies. Med Microbiol Immunol, 182(5):223-232.

[111]SarowskaJ, Futoma-KolochB, Jama-KmiecikA, et al., 2019. Virulence factors, prevalence and potential transmission of extraintestinal pathogenic Escherichia coli isolated from different sources: recent reports. Gut Pathog, 11:10.

[112]SheldonJR, HeinrichsDE, 2012. The iron-regulated staphylococcal lipoproteins. Front Cell Infect Microbiol, 2:41.

[113]ShirshikovaTV, Sierra-BakhshiCG, KamaletdinovaLK, et al., 2021. The ABC-type efflux pump MacAB is involved in protection of Serratia marcescens against aminoglycoside antibiotics, polymyxins, and oxidative stress. mSphere, 6(2):e00033-21.

[114]SongS, WoodTK, 2021. The primary physiological roles of autoinducer 2 in Escherichia coli are chemotaxis and biofilm formation. Microorganisms, 9(2):386.

[115]SongYL, ZhangXL, CaiMH, et al., 2018. The heme transporter HtsABC of group A Streptococcus contributes to virulence and innate immune evasion in murine skin infections. Front Microbiol, 9:1105.

[116]SoniDK, DubeySK, BhatnagarR, 2020. ATP-binding cassette (ABC) import systems of Mycobacterium tuberculosis: target for drug and vaccine development. Emerging Microbes Infect, 9(1):207-220.

[117]SrikantS, 2020. Evolutionary history of ATP-binding cassette proteins. FEBS Lett, 594(23):3882-3897.

[118]SwierLJYM, SlotboomDJ, PoolmanB, 2016. ABC importers. In: George AM (Ed.), ABC Transporters—40 Years on. Springer, Cham, p.3-36.

[119]SwobodaJG, CampbellJ, MeredithTC, et al., 2010. Wall teichoic acid function, biosynthesis, and inhibition. ChemBioChem, 11(1):35-45.

[120]TanakaKJ, SongS, MasonK, PinkettHW, 2018. Selective substrate uptake: the role of ATP-binding cassette (ABC) importers in pathogenesis. Biochimt Biophys Acta (BBA) Biomembr, 1860(4):868-877.

[121]ThélotF, OrlandoBJ, LiYY, et al., 2020. High-resolution views of lipopolysaccharide translocation driven by ABC transporters MsbA and LptB₂FGC. Curr Opin Struct Biol, 63:26-33.

[122]ThomasC, TampéR, 2018. Multifaceted structures and mechanisms of ABC transport systems in health and disease. Curr Opin Struct Biol, 51:116-128.

[123]ThomasC, TampéR, 2020. Structural and mechanistic principles of ABC transporters. Annu Rev Biochem, 89:605-636.

[124]ThomasC, AllerSG, BeisK, et al., 2020. Structural and functional diversity calls for a new classification of ABC transporters. FEBS Lett, 594(23):3767-3775.

[125]TurlinE, HeuckG, SimõesBrandão MI, et al., 2014. Protoporphyrin (PPIX) efflux by the MacAB-TolC pump in Escherichia coli. MicrobiologyOpen, 3(6):849-859.

[126]van VeenHW, 2016. Bacterial ABC multidrug exporters: from shared proteins motifs and features to diversity in molecular mechanisms. In: George AM (Ed.), ABC Transporters—40 Years on. Springer, Cham, p.37-51.

[127]VarelaMF, KumarS, 2019. Strategies for discovery of new molecular targets for anti-infective drugs. Curr Opin Pharmacol, 48:57-68.

[128]VestbyLK, GrønsethT, SimmR, et al., 2020. Bacterial biofilm and its role in the pathogenesis of disease. Antibiotics, 9(2):59.

[129]VijayababuP, SamykannuG, AntonyrajCB, et al., 2018. Patulin interference with ATP binding cassette transferring auto inducer-2 in Salmonella typhi and biofilm inhibition via quorum sensing. Inf Med Unlocked, 11:9-14.

[130]VilletRA, Truong-BolducQC, WangY, et al., 2014. Regulation of expression of abcA and its response to environmental conditions. J Bacteriol, 196(8):1532-1539.

[131]WangQY, WangPF, LiuPP, et al., 2022. Comparative transcriptome analysis reveals regulatory factors involved in Vibrio parahaemolyticus biofilm formation. Front Cell Infect Microbiol, 12:917131.

[132]WangTL, FuGB, PanXJ, et al., 2013. Structure of a bacterial energy-coupling factor transporter. Nature, 497(7448):272-276.

[133]WooJS, ZeltinaA, GoetzBA, et al., 2012. X-ray structure of the Yersinia pestis heme transporter HmuUV. Nat Struct Mol Biol, 19(12):1310-1315.

[134]WoodDW, SetubalJC, KaulR, et al., 2001. The genome of the natural genetic engineer Agrobacterium tumefaciens C58. Science, 294(5550):2317-2323.

[135]XuK, ZhangMH, ZhaoQ, et al., 2013. Crystal structure of a folate energy-coupling factor transporter from Lactobacillus brevis. Nature, 497(7448):268-271.

[136]YamagishiA, NakanoS, YamasakiS, et al., 2020. An efflux inhibitor of the MacAB pump in Salmonella enterica serovar Typhimurium. Microbiol Immunol, 64(3):182-188.

[137]YamanakaH, KobayashiH, TakahashiE, et al., 2008. MacAB is involved in the secretion of Escherichia coli heat-stable enterotoxin II. J Bacteriol, 190(23):7693-7698.

[138]YangJL, HeYP, JiangJ, et al., 2016. Comparative proteomic analysis by iTRAQ-2DLC-MS/MS provides insight into the key proteins involved in Cronobacter sp. biofilm formation. Food Control, 63:93-100.

[139]YangXY, LiN, XuJY, et al., 2019. Lipoprotein SPD_1609 of Streptococcus pneumoniae promotes adherence and invasion to epithelial cells contributing to bacterial virulence. Front Microbiol, 10:1769.

[140]YoshikaiH, KizakiH, SaitoY, et al., 2016. Multidrug-resistance transporter AbcA secretes Staphylococcus aureus cytolytic toxins. J Infect Dis, 213(2):295-304.

[141]ZaynabM, ChenHR, ChenYF, et al., 2021. Signs of biofilm formation in the genome of Labrenzia sp. PO1. Saudi J Biol Sci, 28(3):1900-1912.

[142]ZhengJX, LinZW, SunX, et al., 2018. Overexpression of OqxAB and MacAB efflux pumps contributes to eravacycline resistance and heteroresistance in clinical isolates of Klebsiella pneumoniae. Emerg Microbes Infect, 7(1):1-11.

[143]ZhouZ, SunN, WuSS, et al., 2016. Genomic data mining reveals a rich repertoire of transport proteins in Streptomyces. BMC Genomics, 17(S7):510.